Excessive nitrate content in the ecosystem has raised environmental concerns as a contaminant in soil and water bodies. Therefore, there is a consistent demand for rapid and continuous detection technologies with simple operational processes. In this work, we present a Cu-based nanoarray fabricated by a template-assisted electrodeposition process. By varying the deposition current density, the nanoarray exhibited a hierarchical nano- needle structure with a sharp-needle terminal. Structural analysis confirmed that the metallic Cu nanoneedle has a unique crystal structure compared to the control samples of foil or wire structures. The possible deposition mechanism of nanoneedle was discussed based on the initial crystal formation step during electrodeposition. Furthermore, we explored the sensing performance of the Cu nanoarrays through electrochemical nitrate detection by using cyclic voltammetry (CV). The effect of the needle length on sensing performance was evaluated and the 7 mu m nanoneedle array showed the highest sensitivity of 1.22 mu A mu M- 1 cm- 2 and a wide detection range of 0.25 mM to 16 mM, about 41-fold enhancement compared to the Cu foil. The square-wave voltammetry (SWV) method was further utilized for the low nitrate content detection (0.02 mM to 0.3 mM) and the nano- needle array achieved an improved sensitivity of 6.99 mu A mu M- 1 cm- 2 and an LOD of 26 mu M. The interference study indicated a good tolerance to various interference species. Multiple cycle scans and long term stability tests were conducted using the nanoneedle electrode, which maintained 80 % sensing response after 25 scan tests and close to 95 % sensing response after 21 testing days. The nanoneedle electrode also demonstrated sensing capability in analyzing nitrate species in a real water sample (tap water). Our work provides a convenient method to obtain a hierarchical metallic nanostructure, and the Cu-based nanoarrays show potential for sensitive detection of nitrate across a wide range of applications.

Myeloid-derived suppressor cells (MDSCs) are reported to be responsible for the negative prognosis of colorectal cancer (CRC) patients due to the mediated immunosuppressive tumor microenvironment (TME). The selective and chronic circumvention of tumor-infiltrated MDSCs has potential clinical significance for CRC treatment, which unluckily remains a technical challenge. Because tumor hypoxia makes a significant contribution to the recruitment of MDSCs in tumor sites, a dual oxygen-supplied immunosuppression-inhibiting nanomedicine (DOIN) is demonstrated for overcoming tumor hypoxia, which achieves selective and long-term inhibition of intratumoral recruitment of MDSCs. The DOIN is constructed by the encasement of perfluorooctyl bromide (PFOB) and 4-methylumbelliferone (4-MU) into a TME-responsive amphiphilic polymer. This nanoplatform directly carries oxygen to the tumor region and simultaneously loosens the condensed tumor extracellular matrix for the normalization of tumor vasculature, which selectively remodels the TME toward one adverse to the intratumoral recruitment of MDSCs. Importantly, this nanoplatform offers a long-acting alleviation of the hypoxic TME, chronically avoiding the comeback of tumor-infiltrated MDSCs. Consequently, the immunosuppressive TME is relieved, and T cells are successfully proliferated and activated into cytotoxic T lymphocytes, which boosts a systemic immune response and contributes to lasting inhibition of tumor growth with a prolonged survival span of xenograft. Tumor hypoxia microenvironment help to recruit myeloid-derived suppressor cells (MDSCs) to weaken antitumoral immunity while inhibiting the tumoricidal function of cytotoxic T cells (CTLs). Thus, most MDSCs and least CTLs are shown in upper left part. After dual oxygen-supply through I-4-P@PssP, recruitment of MDSCs is inhibited while CTLs are effectively activated for tumoricidal function (lower right part). image

Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome-wide association study (GWAS) including 14,824 European-ancestry participants. Summary-level data for colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL-12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00-1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin-12p70 levels (IL-12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13-1.43; p < 1.22 × 10-3). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02-1.35; p = .026), macrophage colony-stimulating factor (M-CSF) (OR: 0.85; 95% CI: 0.76-0.96; p = .005), IL-13 (OR: 1.15; 95% CI: 1.02-1.30; p = .028), IL-10 (OR: 1.23; 95% CI: 1.01-1.49; p = .037), and IL-7 (OR: 1.19; 95% CI: 1.02-1.39; p = .024). Our MR studies support that one cytokine IL-12 is significantly associated with CRC risk and that five cytokines VEGF, M-CSF, IL-13, IL-10, and IL-7 are associated with CRC risk.

Some patients may develop adverse events during neoadjuvant chemoradiotherapy combined with immunotherapy, influencing response rates. The roles of intestinal microbiome and its metabolites in therapeutic adverse events remain unclear. We collected baseline fecal samples from 21 patients with adverse events (AE group) and 11 patients without adverse events (Non-AE group). Their microbiota and metabolome were characterized using metagenomic shotgun sequencing and untargeted metabolomics. At the species level, the gut microbiota in the Non-AE group exhibits significantly higher abundance of Clostridium sp. Alistipes sp. and lower abundance of Lachnoclostridium sp. Weissella cibaria, Weissella confusa, compared to the AE group (p < .05). A total of 58 discriminative metabolites were identified between groups. Beta-alanine metabolism was scattered. Boc-beta-cyano-L-alanine and CoQ9 were significantly increased in patients without adverse events, while linoleic acid increased in patients with adverse events. The increased Alistipes sp. in the Non-AE group was positively correlated with Boc-beta-cyano-L-alanine and negatively correlated with linoleic acid (p < .05). We constructed a combined microbiome-metabolite model to distinguish Non-AE and AE patients with an AUC of 0.963 via the random forest algorithm. Our findings provided a novel insight into the interplay of multispecies microbial cluster and metabolites of rectal patients with adverse events in neoadjuvant chemoradiotherapy combined with immunotherapy. These microbiota and metabolites deserve further investigations to reveal their roles in adverse events, providing clues for better treatment scenarios.Trial registration number: ClinicalTrials.gov identifier: NCT05368051

The treatment of diabetic wounds is a major challenge faced by the medical system, and there is a growing interest in developing innovative therapies to accelerate wound healing. Regenerative medicine with cells has shown promising potential in skin repair, with the regenerative properties primarily attributed to the paracrine effects of secreted products, including exosomes. Compared to cell-based approaches, using exosomes as a cell-free therapy for chronic wounds has several advantages. Exosomes can regulate intercellular communication by releasing their contents, including mRNA, miRNA, lipids, and proteins, which further promote wound healing. Exosomes are well explored in biomedical application owing to their advantages such as their biocompatibility and low immunogenicity. However, the common method of exosome administration is through injection, but due to their rapid clearance rate in the body, maintaining the necessary therapeutic concentration around the wound is challenging. Therefore, it is necessary to develop a new biocompatible scaffold as a carrier for extracellular vesicles, allowing them to sustain the therapeutic concentration at chronic non-healing wound sites and continuously promote wound healing. Engineered exosomes are kinds of exosomes modified with internal treated molecules, surface decoration or delivered through engineered platform. In addition, some researchers have further processed and modified exosomes, known as engineered exosomes, with internal treated molecules, surface decoration, or delivery through engineered platforms. Compared to regular exosomes, engineered exosomes have greater advantages in promoting wound healing. In this review, we summarize the molecular mechanisms of exosomes from different sources with varying modifications in wound healing. Advantages and limitations of different engineered exosomes for chronic wound repair were also discussed. Finally, we highlight the challenges and future development directions for translating our knowledge of engineered exosomes into clinical practice.

Anti-programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) immunotherapy has shown promising results in cancer treatment, improving clinical outcomes and prolonging patient survival. However, most patients exhibit low response rates to PD-1/PD-L1 blockade, highlighting the urgent need for new enhancers. Increasing data now demonstrate that inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), a serine proteinase, can enhance the antitumor efficacy of anti-PD-1/PD-L1 immunotherapy.

The morbidity and mortality of gastrointestinal tumours remain high worldwide. Surgical resection is currently the most critical radical therapeutic schedule, while postoperative complications and sentinel lymph node (SLN) identification are closely related to the outcome. Indocyanine green (ICG)-mediated fluorescence imaging is increasingly being used in gastrointestinal surgery. It has been embraced by various surgical disciplines as a potential method to improve lymph node detection and enhance surgical field visualization. ICG can passively concentrate in SLN because of enhanced permeation and retention effects. After excitation by near-infrared light devices, SLN can display higher intensity fluorescence, helping visualization for better lymph node dissection. In addition, visual assessment of intestinal blood flow through ICG may reduce the incidence of anastomotic leakage. Although it has good clinical application, ICG-imaging still faces some problems, such as a higher false-negative rate, poorly targeted biodistribution, and lower fluorescence contrast, due to the lack of active tumour targeting. Thus, different ICG-coupled nanoparticles with inherent characteristics or functional modification-enhanced SLN identification features for gastrointestinal cancers bring benefit through active tumour targeting, superior tumour-background ratio, and high resolution. Nano-ICG combined with potential substances, including enhanced imaging contrast and/or combination therapy (chemotherapy, targeted therapy, immunotherapy, etc.), have been packaged and accumulated in the tumour area through active targeting for multimodal imaging and treatment. In this review, we outline the intraoperative application and possible future nanodirections of ICG in gastrointestinal cancer. The prospects and challenges of nano-ICG diagnostic and therapeutic methods in clinical applications are also discussed.

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer (LARC) patients with microsatellite stable (MSS) / mismatch repair-proficient (pMMR) tumors is an attractive, but debatable strategy. This phase 2, multicenter, prospective, single-arm study enrolled patients from 6 centers from June 2021 to November 2022. Locally advanced rectal cancer (LARC, cT 3-4a N 0 M 0 and cT 1-4a N 1-2 M 0 ) patients aged ≥18 years with the distance from distal border of tumor to anal verge ≤10 cm (identified by Magnetic Resonance Imaging) were qualified for inclusion. The patients received long-course radiotherapy (50 Gy/25 fractions, 2 Gy/fraction, 5 days/week) and three 21-day cycles capecitabine (850–1000 mg/m2, bid, po, day1–14) and three 21-day cycles tislelizumab (200 mg, iv.gtt, day8) as neoadjuvant. Total mesorectal excision (TME) was 6–12 weeks after the end of radiotherapy to achieve radical resection. A total of 50 patients were enrolled in this study. The pathological complete response rate was 40.0% [20/50, 95% confidence interval (CI): 27.61–53.82%], while 15 (30.0%, 95% CI: 19.1–43.75%), 9 (18.0%, 95% CI: 9.77–30.8%), 2 (4.0%, 95% CI: 1.10–13.46%) patients respectively achieved grade 1, 2, and 3 tumor regression. Treatment-related adverse events (TRAEs) occurred in 28 (56.0%) LARC patients, including 26(52.0%) with grade I-II and 2 (4.0%) with grade III (1 with grade 3 immune-related colitis and 1 with grade 3 rash). PD-1 blockade plus long-course chemoradiotherapy (CRT) showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients. A larger randomized controlled study is desired to further validate the above findings.

Introduction Anastomotic leakage (AL) is defined as the failure of complete healing or disruption of the anastomosis subsequent to rectal cancer surgery, resulting in the extravasation of intestinal contents into the intra-abdominal or pelvic cavity. It is a serious complication of rectal cancer surgery, accounting for a considerable increase in morbidity and mortality. The use of fluorescence imaging technology in surgery allows surgeons to better evaluate blood perfusion. However, the conclusions of some existing studies are not consistent, so a consensus on whether the near-infrared indocyanine green (NIR–ICG) imaging system can reduce the incidence of AL is needed.Methods This POSTER trial is designed as a multicentre, prospective, randomised controlled clinical study adhering to the “population, interventions, comparisons, outcomes (PICO)” principles. It is scheduled to take place from August 2019 to December 2024 across eight esteemed hospitals in China. The target population consists of patients diagnosed with rectal cancer through pathological confirmation, with tumours located≤10 cm from the anal verge, eligible for laparoscopic surgery. Enrolled patients will be randomly assigned to either the intervention group or the control group. The intervention group will receive intravenous injections of ICG twice, with intraoperative assessment of anastomotic blood flow using the near-infrared NIR–ICG system during total mesorectal excision (TME) surgery. Conversely, the control group will undergo conventional TME surgery without the use of the NIR-ICG system. A 30-day follow-up period postoperation will be conducted to monitor and evaluate occurrences of AL. The primary endpoint of this study is the incidence of AL within 30 days postsurgery in both groups. The primary outcome investigators will be blinded to the application of ICG angiography. Based on prior literature, we hypothesise an AL rate of 10.3% in the control group and 3% in the experimental group for this study. With a planned ratio of 2:1 between the number of cases in the experimental and control groups, and an expected 20% lost-to-follow-up rate, the initial estimated sample size for this study is 712, comprising 474 in the experimental group and 238 in the control group.Ethics and dissemination This study has been approved by Ethics committee of Beijing Friendship Hospital, Capital Medical University (approval number: 2019-P2-055-02). The results will be disseminated in major international conferences and peer-reviewed journals.Trial registration number NCT04012645.

Mesenchymal stem cells (MSCs) have been recognized as a cell therapy with the potential to promote skin healing. MSCs, with their multipotent differentiation ability, can generate various cells related to wound healing, such as dermal fibroblasts (DFs), endothelial cells, and keratinocytes. In addition, MSCs promote neovascularization, cellular regeneration, and tissue healing through mechanisms including paracrine and autocrine signaling. Due to these characteristics, MSCs have been extensively studied in the context of burn healing and chronic wound repair. Furthermore, during the investigation of MSCs, their unique roles in skin aging and scarless healing have also been discovered. In this review, we summarize the mechanisms by which MSCs promote wound healing and discuss the recent findings from preclinical and clinical studies. We also explore strategies to enhance the therapeutic effects of MSCs. Moreover, we discuss the emerging trend of combining MSCs with tissue engineering techniques, leveraging the advantages of MSCs and tissue engineering materials, such as biodegradable scaffolds and hydrogels, to enhance the skin repair capacity of MSCs. Additionally, we highlight the potential of using paracrine and autocrine characteristics of MSCs to explore cell-free therapies as a future direction in stem cell-based treatments, further demonstrating the clinical and regenerative aesthetic applications of MSCs in skin repair and regeneration.

Immune checkpoint therapy, such as programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) blockade, has achieved remarkable results in treating various tumors. However, most cancer patients show a low response rate to PD-1/PD-L1 blockade, especially those with microsatellite stable/mismatch repair-proficient colorectal cancer subtypes, which indicates an urgent need for new approaches to augment the efficacy of PD-1/PD-L1 blockade. Cholesterol metabolism, which involves generating multifunctional metabolites and essential membrane components, is also instrumental in tumor development. In recent years, inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), a serine proteinase that regulates cholesterol metabolism, has been demonstrated to be a method enhancing the antitumor effect of PD-1/PD-L1 blockade to some extent. Mechanistically, PCSK9 inhibition can maintain the recycling of major histocompatibility protein class I, promote low-density lipoprotein receptor-mediated T-cell receptor recycling and signaling, and modulate the tumor microenvironment (TME) by affecting the infiltration and exclusion of immune cells. These mechanisms increase the quantity and enhance the antineoplastic effect of cytotoxic T lymphocyte, the main functional immune cells involved in anti-PD-1/PD-L1 immunotherapy, in the TME. Therefore, combining PCSK9 inhibition therapy with anti-PD-1/PD-L1 immunotherapy may provide a novel option for improving antitumor effects and may constitute a promising research direction. This review concentrates on the relationship between PCSK9 and cholesterol metabolism, systematically discusses how PCSK9 inhibition potentiates PD-1/PD-L1 blockade for cancer treatment, and highlights the research directions in this field.

Background: Accurate evaluation of the response to preoperative treatment enables the provision of a more appropriate personalized therapeutic schedule for locally advanced rectal cancer (LARC), which remains an enormous challenge, especially neoadjuvant immunotherapy plus chemoradiotherapy (nICRT). Methods: This prospective, multicenter cohort study enrolled patients with LARC from 6 centers who received nICRT. The dynamic variation in the gut microbiome during nICRT was evaluated. A species-level gut microbiome prediction (SPEED) model was developed and validated to predict the pathological complete response (pCR) to nICRT. Findings: A total of 50 patients were enrolled, 75 fecal samples were collected from 33 patients at different time points, and the pCR rate reached 42.4% (14/33). Lactobacillus and Eubacterium were observed to increase after nICRT. Additionally, significant differences in the gut microbiome were observed between responders and non-responders at baseline. Significantly higher abundances of Lachnospiraceae bacterium and Blautia wexlerae were found in responders, while Bacteroides, Prevotella, and Porphyromonas were found in non-responders. The SPEED model showcased a superior predictive performance with areas under the curve of 98.80% (95% confidence interval [CI]: 95.67%-100%) in the training cohort and 77.78% (95% CI: 65.42%-88.29%) in the validation cohort. Conclusions: Programmed death 1 (PD-1) blockade plus concurrent long-course CRT showed a favorable pCR rate and is well tolerated in microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) patients with LARC. The SPEED model can be used to predict the pCR to nICRT based on the baseline gut microbiome with high robustness and accuracy, thereby assisting clinical physicians in providing individualized management for patients with LARC. Funding: This research was funded by the China National Natural Science Foundation (82202884).

Wound healing is an intricate process that involves interactions between various types of cell and molecular mechanisms. When wounds fail to heal effectively or develop into chronic wounds, they can cause significant pain and discomfort to patients and impose a heavy burden on society. The development of innovative treatment approaches can effectively facilitate the wound healing process, improve patient well-being, and reduce the societal burden. The progress of nanotechnology in the field of biomedical science has brought about vast prospects for its applications in wound healing. This article provides a comprehensive review of the physiological wound healing process and the application of nanomaterials in wound healing and systematically elucidates the mechanisms of nanomaterials at different stages of wound healing. Furthermore, this study highlights the current limitations and deficiencies of using nanomaterials in wound treatment. Considering the present state of utilizing nanomaterials for wound healing purposes, this review proposes new perspectives for future research and provides valuable directions and innovative ideas for researchers in this field.

PURPOSE:We primary aimed to synthesise the available data, assess the effectiveness of different mesh materials in prophylactic mesh placement, and rank these materials according to the incidence of parastomal hernia (PSH) and other stoma complications. METHOD:This network meta-analysis performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Four databases were searched for randomised controlled trials of prophylactic mesh placement. The aggregated results were performed in the STATA routine for Bayesian hierarchical random effects models. RESULT:Thirteen randomised controlled trials from 1203 articles, met the inclusion criteria, including 681 cases without meshes, 65 cases with mesh material of xenogeneic acellular dermis (porcine/bovine), 27 cases with polypropylene/PG910, 114 cases with polypropylene/polyglecaprone (Monocryl), 117 cases with polypropylene/cellulose (ORC), 233 cases with polypropylene, and 35 cases with polypropylene/PVDF. In network A, compared with no mesh, only polypropylene (RR 0.24, 95% CI 0.04-0.80) were significantly associated with a reduction in the incidence of PSH. In network B, no statistical difference regarding stoma complications was found between mesh and no mesh. CONCLUSION:Based on the network meta-analysis and ranking results, the polypropylene mesh material exhibited the best performance. However, this conclusion needs to be confirmed with larger sample sizes and high-quality randomised controlled trials.

The field of nanotechnology continues to grow with the ongoing discovery and characterization of novel nanomaterials with unconventional size-dependent properties; however, the ability to apply modern manufacturing strategies for practical device design of these nanoscale structures is significantly limited by their small size. Although interconnection has been previously demonstrated between nanoscale components, such approaches often require the use of expensive oxidation-resistant noble metal materials and time-consuming or untargeted strategies for welded interconnection such as laser ablation or plasmonic resonance across randomly oriented component networks. In this work, a three-segment gold-nickel-gold nanowire structure is synthesized using templated electrodeposition and modified via monolayer-directed aqueous chemical reduction of tin solder selectively on the gold segments. This core/shell nanowire structure is capable of directed magnetic assembly tip-to-tip and along substrate pads in network orientation. Upon infrared heating in a flux vapor atmosphere, the solder payload melts and establishes robust and highly conductive wire-wire joints. The targeted solder deposition strategy has been applied to various other multi-segment gold/nickel nanowire configurations and other metallic systems to demonstrate the capability of the approach. This core/shell technique of pre-loading magnetically active nanowires with solder material simplifies the associated challenges of size-dependent component orientation in the manufacture of nanoscale electronic devices.

e15612 Background: Thymalfasin, as an immunomodulator, can enhance the anti-tumor effects of T cells, NK cells, and macrophages. This study explored the efficacy and safety of a new adjuvant treatment regimen for rectal cancer, combining thymalfasin with chemoradiotherapy and the PD-1 inhibitor tislelizumab, and its impact on the immune microenvironment. Methods: This retrospective study enrolled 26 patients with locally advanced rectal cancer from March 2021 to December 2022. Thirteen patients received long-course concurrent chemoradiotherapy combined with concurrent tislelizumab treatment, and thirteen received thymalfasin combined with long-course chemoradiotherapy and concurrent tislelizumab treatment (radiotherapy: 50 Gy/25 f; capecitabine, 1000mg/m2, bid; tislelizumab: 200mg, every 21 days, 3 cycles; Thymalfasin: 1.6mg, biw). The postoperative pathological complete response rate (ypT0N0M0), tumor regression grade (AJCC 8th Version), and adverse event (CTCAE 4.0) incidence were assessed, along with changes in the immune microenvironment before and after treatment using multiplex immunofluorescence staining. Results: The pathological complete response rates observed postoperatively were 61.5% in the treatment group, compared to 38.5% in the control group. The distribution of tumor regression grades 0, 1, 2, and 3 was 69.2%, 15.4%, 15.4%, 0% in the treatment group respectively, and 38.5%, 38.5%, 7.7%, 15.4%, in the control group respectively. The adverse event rates reached 84.6% in the treatment group and 76.9% in the control group, with all events classified as either grade 1 or 2 according to the CTCAE 4.0. Significant reductions in CD4+PD1+ cell density (p < 0.001), CD8+PD1+ cell density (p = 0.024), CD68+ cell density (p = 0.007), the CD4/CD8 ratio (p < 0.001), and the CD68+CD86+/CD68+CD163+ ratio (p = 0.012) were demonstrated through multiplex immunofluorescence following neoadjuvant treatment. The treatment group exhibited significant decreases in CD8+PD1+ cell density (p = 0.025) and CD68+CD163+ cell density (p = 0.021) when compared to the control group. Conclusions: Thymalfasin combined with chemoradiotherapy and tislelizumab as a neoadjuvant treatment regimen for patients with locally advanced lower rectal cancer has shown favorable efficacy and safety. Neoadjuvant chemoradiotherapy combined with immunotherapy restored T cell function and reduced the proportion of tumor-associated macrophages, but macrophages polarized towards an M2-like phenotype. Thymalfasin may play a role by synergizing with the PD-1 inhibitor to restore cytotoxic T cell function and block macrophage polarization towards M2 cells. Clinical trial information: NCT06024356 .

The extensive usage of nitrogen-based fertilizers, food preservatives and explosive chemicals in various industries has led to the accumulation of nitrate in the ecosystems, especially in soil and water bodies. Several severe environmental and human health issues, including eutrophication, diseases related to N-nitroso compounds (such as Cancer, Parkinson and Gastritis) and blue-baby syndrome (methemoglobinemia), have arisen from the excessive nitrate concentration in the environment. Consequently, various government and regulatory agencies, such as the U.S. Environmental Protection Agency (EPA), have established the maximum nitrate ion concentration in drinkable water at 44 mg/L (0.71 mM). In this context, an accurate monitoring of the level of nitrate becomes important in environmental pollution control, food, clinical analysis, and other industries. While the spectroscopy techniques are of the most use due to its high precision and low limit of detection (LOD), these methods frequently require skilled workforces and specific instrumentations to operate. The electrochemical sensors benefit from recent developments of new nanomaterials to detect nitrate with a quick response, ability of continuously monitoring, small and simple instrumentation as well as easy to use. Several studies have utilized different strategies to fabricate Cu-based nanostructures (such as nanoparticles, nanoclusters, nanowires, and single-crystals) to achieve a low LOD. However, the sensitivity that has been achieved so far is still relatively low compared to the requirements for the real sampling applications. In this work, we utilized a one-step electrodeposition method to prepare Cu-based nano-array electrodes with high active surface sites, aiming for a fast and sensitive electrochemical detection of nitrate. The morphology of the array can be fine-tuned between nanoneedle and nanowire structures ( Figure 1a and 1b ). The x-ray diffraction (XRD) measurements indicate that the Cu-based nanoneedle array exhibited an abundant Cu(220) facet than the nanowire systems, which is usually associated with the active edge sites on copper ( Figure 1c ). The nanoneedle array was used for nitrate sensing via Cyclic Voltammetry methods which showed a sensitivity of 2.8 μA/μM*cm 2 , about 5-fold higher than the Cu foil control electrode ( Figure 1d ). The main reason of the sensitivity enhancement is that the nanoneedle structure resulted in a 30 times enrichment in the surface area compared to the Cu foil as shown in the electrochemical surface area (ECSA) measurement. Overall, our study provides a novel and convenient design of highly ordered Cu nanoneedle array structure for the sensitive electrochemical detection of nitrate. Figure 1

Background Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer, with modest benefits on tumor regression and survival. Since chemoradiotherapy combined with immune checkpoint inhibitors has been reported to have synergic effects. This study aims to explore the safety and efficacy of long-course chemoradiotherapy combined with concurrent tislelizumab as a neoadjuvant treatment regimen for patients with locally advanced rectal cancer. Methods This manuscript reported the interim result of a prospective, multicenter, single-arm, phase II trial. Patients with mid-to-low locally advanced rectal cancer with clinical stages of cT3-4a N0M0 or cT1-4a N1-2M0 were included. The patients received long-course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles of capecitabine (1000 mg/m2, bid, day1-14) plus concurrent three 21-day cycles of tislelizumab (200 mg, day8), followed by a radical surgery 6-8 weeks after radiotherapy. The primary endpoint was the pathological complete response rate. (Clinical trial number: NCT04911517) Results A total of 26 patients completed the treatment protocol between April 2021 and June 2022. All patients completed chemoradiotherapy, 24 patients received three cycles of tislelizumab, and 2 patients received two cycles. The pathological complete remission (ypT0N0) was achieved in 50% (13/26) of the patients with all proficient mismatch repair tumors. The immune-related adverse event occurred in 19.2% (5/26) of patients. Patients with no CEA elevation or age less than 50 were more likely to benefit from this treatment regimen. Conclusion Long-course chemoradiotherapy combined with concurrent tislelizumab in patients with locally advanced low rectal cancer had favorable safety and efficacy, and does not increase the complication rate of surgery. Further study is needed to confirm these results.

Metallic catalyst modification by organic ligands is an emerging catalyst design in enhancing the activity and selectivity of electrocatalytic carbon dioxide (CO2) reactive capture and reduction to value-added fuels. However, a lack of fundamental science on how these ligand-metal interfaces interact with CO2 and key intermediates under working conditions has resulted in a trial-and-error approach for experimental designs. With the aid of density functional theory calculations, we provided a comprehensive mechanism study of CO2 reduction to multicarbon products over aminothiolate-coated copper (Cu) catalysts. Our results indicate that the CO2 reduction performance was closely related to the alkyl chain length, ligand coverage, ligand configuration, and Cu facet. The aminothiolate ligand-Cu interface significantly promoted initial CO2 activation and lowered the activation barrier of carbon-carbon coupling through the organic (nitrogen (N)) and inorganic (Cu) interfacial active sites. Experimentally, the selectivity and partial current density of the multicarbon products over aminothiolate-coated Cu increased by 1.5-fold and 2-fold, respectively, as compared to the pristine Cu at -1.16 VRHE, consistent with our theoretical findings. This work highlights the promising strategy of designing the ligand-metal interface for CO2 reactive capture and conversion to multicarbon products.

Wound dressing is an important tool for wound management. Designing wound dressings by combining various novel materials and drugs to optimize the peri-wound environment and promote wound healing is a novel concept. Hydrogels feature good ductility, high water content, and favorable oxygen transport, which makes them become some of the most promising materials for wound dressings. In addition, nanomaterials exhibit superior biodegradability, biocompatibility, and colloidal stability in wound healing and can play a role in promoting healing through their nanoscale properties or as carriers of other drugs. By combining the advantages of both technologies, several outstanding and efficient wound dressings have been developed. In this paper, we classify nano-based hydrogel dressings into four categories: hydrogel dressings loaded with a nanoantibacterial drug; hydrogel dressings loaded with oxygen-delivering nanomedicines; hydrogel dressings loaded with nanonucleic acid drugs; and hydrogel dressings loaded with other nanodelivered drugs. The design ideas, advantages, and challenges of these nano-based hydrogel wound dressings are reviewed and analyzed. Finally, we envisaged possible future directions for wound dressings in the context of relevant scientific and technological advances, which we hope will inform further research in wound management.