BACKGROUND:Keloids are pathological scars with incompletely understood pathogenesis. This study aims to identify the key genes and regulatory networks potentially involved in keloid formation by integrating single-cell transcriptomics (scRNA-seq), protein quantitative trait loci (pQTL), Mendelian randomization (MR) analyses, colocalization, and comprehensive functional characterization. METHODS:Single-cell RNA sequencing data (GSE181297, GSE163973) and bulk transcriptomic data (GSE145725) were obtained from the GEO database. These datasets, which included both keloid lesions and normal scar samples from distinct individuals, were subjected to rigorous quality control and cell annotation. Intercellular communication was analyzed using CellChat, and co-expression networks were constructed via hdWGCNA. To identify potential causal genes, MR analysis was performed by integrating pQTL data from the deCODE database with GWAS summary statistics (GCST90018874), followed by colocalization, sensitivity analysis, and reverse validation. Further functional characterization of potential key genes was conducted through Gene Set Enrichment Analysis (GSEA), immune infiltration analysis, transcription factor (TF) regulatory network inference, and pseudotime trajectory analysis. RESULTS:92 659 high-quality cells were retained, revealing seven major cell types with fibroblasts showing the most extensive intercellular interactions. Mendelian randomization identified 11 genes causally linked to keloid risk, with genetically determined downregulation of SSR1 and SRA1 associated with increased susceptibility. SRA1 was enriched in cell cycle, nucleocytoplasmic transport, and ribosome biogenesis in eukaryotes, while SSR1 was implicated in complement/coagulation cascades, the NOD-like receptor signaling pathway, and viral protein interaction with cytokine and cytokine receptors. Immunoinfiltration, TF network and motif analysis, and pseudotime analysis further characterized their regulatory roles in immune microenvironment modulation and cell differentiation. CONCLUSIONS:This multi-omics study identifies SRA1 and SSR1 as potential key protective genes in keloid pathogenesis. These genes may contribute to inhibiting disease progression through modulation of cell proliferation, the immune microenvironment, and cellular signaling pathways. These findings provide novel mechanistic insights and potential immunotherapeutic targets for keloids.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a bat-origin porcine enteric alphacoronavirus first identified in Guangdong, China in 2017, which causes severe watery diarrhea and high mortality in neonatal piglets, leading to in substantial economic losses to the global swine industry. Here, we report that SADS-CoV nsp10 functions as an IFN-λ1 antagonist. Specifically, nsp10 suppressed IFN-λ1 production independently of its zinc finger domains. Furthermore, nsp10 inhibits MAVS- and IRF1-driven IFN-λ1 expression within the RLR signaling pathway. Nsp10 blocks poly (I:C)-induced nuclear translocation of IRF1, although no direct physical interaction is detected between the two proteins. Pull-down assays combined with mass spectrometry identified hnRNPU as a nsp10-interacting protein and their direct interaction was verified by co-immunoprecipitation (Co-IP). hnRNPU alone inhibits IFN-λ1 production and synergizes with nsp10 to enhance this suppression, consequently facilitating SADS-CoV replication. Collectively, our findings uncover a previously unrecognized immune evasion mechanism employed by SADS-CoV and provide a potential therapeutic target for controlling coronavirus infections.

Photodynamic therapy (PDT), a non-invasive therapeutic modality, has significantly improved skin cancer treatment in recent years. Nonetheless, the limitations associated with conventional photosensitizers, such as their substantial dependence on oxygen and restricted light penetration, continue to pose considerable challenges for clinical applications. Herein, five Iridium(III) complexes have been developed as type I photosensitizers for two-photon PDT targeting melanoma. These complexes exhibit notable two-photon absorption (TPA) cross-sections (σ2 ≥ 100 GM) and high yields of reactive oxygen species (ROS) under hypoxic conditions, leading to mitochondrial damage and subsequent apoptosis through ROS generation with low doses of single or two-photon excitation. Notably, Ir4@PEG exhibits an IC50 value of 2.1 μM and a phototoxicity index (PI) of 47 under hypoxic conditions. Cellular assays indicate that Ir4@PEG initially targets and localizes within lysosomes, where the lysosomal membrane is subsequently compromised upon light stimulation, resulting in Ir4 transferring and damaging mitochondria, causing cell apoptosis. Additionally, Ir4@PEG demonstrates improved tumor penetration, significant ROS production, and marked phototoxicity in hypoxic three-dimensional tumor spheroids. These findings provide new insights into designing oxygen-independent, metal-based two-photon photodynamic therapies against hypoxic melanoma.

The prevalence of bacterial resistance, driven by extensive antibiotic overuse, significantly threatens patient safety. Consequently, it is urgent and helpful for the clinician to develop new antibacterial therapy techniques. In this study, we designed a novel photodynamic antibacterial therapeutic strategy by functionalizing D-alanine on Iridium(III) complexes. The synergistic D-alanine metabolic labeling function and two-photon photodynamic eradication capacity of Ir(III) complexes enable bacterial imaging and elimination of bacterial pathogens within host cells. These two-photon photoantibiotics effectively inhibit bacterial biofilm formation and efficiently eliminate intracellular bacterial infections in macrophages, enabling real-time dynamic monitoring of antimicrobial efficacy. Furthermore, both in vitro and in vivo experiments demonstrated superior antibacterial performance compared to conventional antibiotics alone.

Mycobacterium avium (M. avium) is emerging as an opportunistic pathogen and has been grouped with the nontuberculosis mycobacteria (NTM). Tuberculosis (TB), caused by Mycobacterium tuberculosis, primarily affects elderly individuals with chronic lung disease and remains one of the leading causes of death in many regions worldwide. Distinguishing between NTM infection and TB is challenging due to similar clinical manifestations and histopathological characteristics. Talaromyces marneffei (T. marneffei) is a pathogenic fungus causing devastating infection, primarily in immunocompromised individuals. Few reports describe disseminated co-infection of M. avium and T. marneffei in HIV-negative persons. Herein, we present a case of an HIV-negative Chinese woman who initially presented with chronic cough, sputum production, and recurrent low-grade fever, which was initially misdiagnosed as TB. After three years of anti-TB treatment, her situation progressed, and she developed multiple subcutaneous abscesses throughout the body, including the brain. Subsequent bacterial culture and molecular diagnostic techniques confirmed the presence of NTM, specifically identified as M. avium. However, despite receiving anti-M. avium therapy remained ineffective until co-infection with T. marneffei was eventually diagnosed. The patient responded well to anti-M. avium therapy combined with antifungal agents after two weeks. Unfortunately, she was lost during the follow-up. Strict adherence to the established clinical diagnostic guidelines for tuberculosis is essential. Early implementation of ‌microbial culture and molecular diagnostic tools plays a critical role in distinguishing TB from NTM infections, particularly in patients who do not respond adequately to anti-tuberculosis therapies. In addition, clinicians should remain vigilant for potential co-infections when inflammatory markers fail to decline or disease progression continues despite adequate anti-infective treatment.

We retrospectively reviewed the medical records of patients with hand-foot-and-mouth disease (HFMD) and varicella treated in a general hospital in Guangzhou, China between 2017 and 2023 to evaluate the effect of the coronavirus disease 2019 (COVID-19) on the epidemiology of HFMD and varicella in Guangzhou. The epidemiological characteristics of HFMD and varicella before (2017–2019), during (2020–2022), and after (2023) the pandemic were compared. In total, 1731 cases of HFMD and 1043 cases of varicella were reported before the COVID-19 pandemic (2017–2019), with average reporting rates of 0.08% and 0.05%, respectively. During the COVID-19 pandemic (2020–2022), the number of reported cases of HFMD and varicella decreased to 571 and 389, respectively, with average reporting rates of 0.03% and 0.02%, respectively, which were significantly different from those in the pre-pandemic period (P < 0.001). In the post-pandemic period (2023), the reporting rate of HFMD was 0.07%, showing a marked increase compared with that in 2022 (P < 0.001). However, the difference in the reporting rate of varicella in 2023 did not differ significantly from that in 2022 (P =0.204). These results suggest that non-pharmaceutical interventions implemented during the COVID-19 pandemic might be helpful in preventing the spread of HFMD and varicella.

The H9N2 subtype of avian influenza virus (AIV) causes severe immunosuppression and high mortality in view of its frequent co-infection with other pathogens, resulting in significant economic losses in the poultry industry. Current vaccines provide suboptimal immune protection against H9N2 AIV owing to antigenic variations, highlighting the urgent need for safe and effective antiviral drugs for the prevention and treatment of this virus. This study aimed to investigate the inhibitory effects of Hypericum japonicum extract on H9N2 AIV. Our findings revealed that the extract obtained through resin column separation using 60

Background Mycobacterium avium (M. avium) is emerging as an opportunistic pathogen and has been grouped with the nontuberculosis mycobacteria (NTM). Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), primarily affects elderly individuals with chronic lung disease and remains one of the leading causes of death in many regions worldwide. Distinguishing between NTM infection and drug-resistant TB is challenging due to similar manifestations and resistance to conventional anti-tuberculosis therapies (ATT). Talaromyces marneffei (T. marneffei) is a pathogenic fungus causing devastating infection, primarily in immunocompromised individuals. Few reports describe disseminated co-infection of M. avium and T. marneffei in HIV-uninfected persons. Case presentation: Herein, we present a case study of an HIV-negative Chinese woman who initially presented with chronic cough, sputum production, and recurrent low-grade fever, which was initially diagnosed as TB. After three years of anti-TB treatment, her situation progressed, and she developed multiple subcutaneous abscesses throughout the body, including the brain. Subsequent bacterial culture and genetic analysis confirmed the presence of NTM specifically identified as M. avium. However, despite receiving anti-NTM treatment, it remained ineffective until co-infection with T. marneffei was eventually diagnosed. Conclusions Early utilization of genetic diagnostic methods is necessary to detect the possibility of NTM infections, especially when patients do not respond adequately to ATT. It is also crucial to remain vigilant for co-infections when the disease progresses despite ongoing anti-NTM treatment.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus that causes acute watery diarrhea, vomiting, and dehydration in newborn piglets. The type III interferon (IFN-λ) response serves as the primary defense against viruses that replicate in intestinal epithelial cells. However, there is currently no information available on how SADS-CoV modulates the production of IFN-λ. In this study, we utilized IPI-FX cells (a cell line of porcine ileum epithelium) as an in vitro model to investigate the potential immune evasion strategies employed by SADS-CoV against the IFN-λ response. Our results showed that SADS-CoV infection suppressed the production of IFN-λ1 induced by poly(I:C). Through screening SADS-CoV-encoded proteins, nsp1, nsp5, nsp10, nsp12, nsp16, E, S1, and S2 were identified as antagonists of IFN-λ1 production. Specifically, SADS-CoV nsp1 impeded the activation of the IFN-λ1 promoter mediated by MAVS, TBK1, IKKε, and IRF1. Both SADS-CoV and nsp1 obstructed poly(I:C)-induced nuclear translocation of IRF1. Moreover, SADS-CoV nsp1 degraded IRF1 via the ubiquitin-mediated proteasome pathway without interacting with it. Overall, our study provides the first evidence that SADS-CoV inhibits the type III IFN response, shedding light on the molecular mechanisms employed by SADS-CoV to evade the host immune response.

Introduction: Acrodermatitis continua of Hallopeau (ACH) is an uncommon chronic cutaneous disorder. Up to date, its treatment is still difficult and frustrating although various topical and systemic agents alone or in different combinations have been tried with variable benefits. Herein, we report two cases of ACH successfully treated with calcipotriol/betamethasone ointment. Case presentation: Two cases of ACH were characterized by thumb involvement alone and showed an excellent response to calcipotriol/betamethasone ointment (1 g: calcipotriol 50 µg and betamethasone 0.5 mg). Discussion: Treatment of ACH is challenging for physicians. Multiple systemic therapies and topical drugs have been applied, however, no universally effective treatment regimen has yet been established for long-lasting remission. Combination of calcipotriol and betamethasone is more effective in treating psoriasis than the individual components alone, and the current 2 cases with ACH were reported to be treated successfully by the calcipotriol/betamethasone ointment. Conclusion: Topical calcipotriol/betamethasone compound is an optional agent for the treatment of ACH with a novel effect.

BACKGROUND:The most visible sign of facial aging is often seen in the periocular area. However, periocular rejuvenation remains challenging due to the particularity of periocular anatomic locations.AIMS:We aimed to evaluate the efficacy and safety of the fractional-ablative CO2 laser-facilitated recombinant human collagen permeation in periocular rejuvenation.PATIENTS/METHODS:This 3-month prospective single-blinded and self-controlled trial enrolled 26 patients with periocular aging who underwent the treatments of fractional-ablative CO2 laser along with laser-facilitated recombinant human collagen permeation. Following the treatments, the patients were quantitatively assessed by various periocular skin aging indices before and after the treatment and monitored for any related adverse events.RESULTS:The patients showed significant improvements with the periocular skin aging indices 3 months after the treatments, which were detailed with a 47.3% decrease in lower eyelid skin rhytids, a 41.4% decrease in the lower eyelid skin texture, a 35.0% decrease in the static crow's feet, a 29.3% decrease in the amount of upper eyelid laxity, and a 20.2% increase in the MRD1 as compared with baseline (p < 0.05). Moreover, total skin thickness under ultrasound was increased in both upper and lower eyelids (5.6% and 3.3%, p < 0.05, respectively). Moreover, six patients (23.1%, 6/26) had erythema for 2 weeks, and two (2/26, 7.7%) had mild hyperpigmentation for 3 months.CONCLUSIONS:Fractional-ablative CO2 laser combined with laser-facilitated recombinant human collagen permeation can be a safe and effective treatment for periocular rejuvenation.

Pubic Lice A 59-year-old man presented with a 4-week history of severe itching in his pubic region after sexual contact with a new partner. On examination, nits and crab-shaped lice (shown in a video) were seen attached to pubic hairs.

A 25-year-old unmarried man was referred because of 1-week history of mildly sore throat, without association of systemic symptoms. He had an oral sex with a man 3 weeks before his presentation. His-past medical histories were unremarkable. Examination showed a well-delimited plaque with central ulceration on the right retropharyngeal wall, covered with white pseudomembranes and surrounded by erythema (Figure 1). No other rashes were detected elsewhere. Laboratory tests for complete blood cell count, erythrocyte sedimentation rate, biochemistry profiles, C-reactive protein, anti-nuclear antibodies, auto-antibodies and HIV were either within normal limits or negative.

Scabies is a contagious skin condition caused by Sarcoptes scabiei, and it is always associated with an intense, unbearable, nocturnal deteriorating itch. Its presentations include classic burrows, erythema, pruritic papules, pustules, vesicles, and inflammatory nodules, with diffuse or localized distribution on the finger webs, wrist flexors, elbows, axillae, buttocks, genitalia, and breasts. Nodular scabies is an uncommon clinical variant of scabies. Its management is still challenging for some patients up to date, although topical, intralesional or systemic corticosteroids, topical calcineurin inhibitors, and crotamiton as well as cryotherapy alone or in different combinations are used. We here report five male patients of nodular scabies, aged between 14 and 25 years, who had classical scabies that had been cured by sulfur ointment for at least 4 weeks except for their itching nodules, and their residual pruritic nodules also failed in previous treatments including antihistamines, topical applying and intralesional injection of steroids as well as topical tacrolimus in different combinations before being recruited to this study. The patients were administered tofacitinib 5 mg, twice a day, which led to excellent and rapid improvement for both lesions and symptoms after 1-4 weeks of treatment, respectively, without any associations. During 6 months of follow-up, only one had re-infection of scabies associated with nodules that were cured by sulfur ointment and tofacitinib again. No adverse reaction was observed. The present results suggested that tofacitinib might be a potential agent for nodular scabies with excellent response.

An encapsulation of cyclometalated iridium( iii ) prodrugs into selenium nanoparticles, which were further camouflaged with cancer cell membranes, was developed for synergistic chemotherapy and two-photon photodynamic therapy against melanoma.

A 71-year-old man presented with 11 years of asymptomatic facial ulcer that was a tiny papule initially, then increased in size slowly with central erosion over the years. A few months before the presentation, a subsequent papule in the previous lesion presented which was asymptomatic and enlarged in size gradually. His medical and family histories were unremarkable. Cutaneous examination revealed that an ulcerated plaque of about 10 cm × 6 cm in across located on the left cheek, associated with irregularly raised circular hyperpigmented papules around and scars on the centre, and a red erosive nodule-plaque about 2.5 cm in diameter localized on the left lower quadrant of the ulcer near the middle of mandible (Figure 1). Computed tomography scan showed no lymphatic metastasis. The lesion was completely excised without recurrence in a 9-year follow-up.

Erythermalgia, a rare painful disorder, is characterized by recurrent pain attacking, warmth, and erythema that mainly involves the distal extremities. Red ear syndrome shares similar clinical features of erythermalgia afflicting the external ear with unilateral/bilateral distribution. The treatments of both diseases are still difficult without controlled therapeutics available up to date. A 12-year-old boy was referred because of 3 years of recurrent attacking of painful erythema and warmth that involved the ears alone, the episodes occurred several times daily with duration of dozens of minutes to hours for each flare. The symptoms could be relieved by cold water and triggered by heat stimuli as well as exciting and movement, and showed mild response to gabapentin, celecoxib, and topical lidocaine compounds in combination, but moderate to blocking injection of botulinum toxin to nervus auricularis magnus. However, systemic itraconazole 200 mg daily resulted in an excellent response after 5-week treatment, leading to milder erythema, warmth and burning sensation, shorter duration, and fewer relapses. The treatment continued for 6 months and then itraconazole was decreased to 100 mg daily for another 6 months until it was stopped, with maintenance of good conditions. In 3 months of follow-up after the treatment ceased, the patient had only 7 to 8 attacks over 10 days presenting as tolerable erythema that lasted for less than 10 min and relieved spontaneously, with absence of warmth and no need of treatment. We considered the patient to be a variant of erythermalgia rather than a red ear syndrome. The results showed that erythermalgia might involve the ears alone and itraconazole might be a potential agent for its treatment.

Chiral rhodium(III)-azobenzene complexes that are able to intercalate into DNA were developed. Upon light exposure, the azobenzene moiety of the metal complexes can photoisomerize from the trans-form to the cis-form, and strongly stabilize the DNA double-helix and modulate DNA transcription. This study presents the first example of metal-based photoswitchable DNA molecular locks.

目的:通过检测咪喹莫特诱导的银屑病小鼠模型皮损VEGFR?1及VEGFR?2的表达水平,为研究银屑病血管机制方向提供实验基础.方法:Balb/c小鼠随机分为实验组(n=7)和正常对照组(n=5),实验组使用咪喹莫特乳膏诱导建立银屑病小鼠模型.免疫组化染色检测VEGFR?1及VEGFR?2在小鼠皮肤中的表达及分布,并对VEGFR?1和VEGFR?2染色阳性的血管进行计数以及与血管、表皮厚度之间的相关性.结果:实验组表皮、真皮血管与毛囊均过度表达VEGFR?1(P<0.05)和VEGFR?2(P<0.05);实验组VEGFR?1血管染色阳性率较VEGFR?2血管染色阳性率高(P<0.05);实验组VEGFR?1及VEGFR?2的免疫组化染色累积光密度值(IOD值)分别与小鼠微血管数量、表皮厚度存在正相关(P<0.05).结论:银屑病小鼠皮损中VEGFR?1与VEGFR?2过度表达,其表达强度与总血管数量、表皮角质形成细胞的增殖程度呈正相关.

BackgroundPsoriasis and atherosclerosis have overlapping pathophysiological mechanisms. However, the association between psoriasis and coronary artery calcification (CAC), a hallmark of atherosclerosis and a predictor of poor cardiovascular prognosis, remains to be determined. We performed a systematic review and meta-analysis to comprehensively evaluate the association between these related inflammatory conditions.MethodsObservational studies evaluating the relationship between psoriasis and CAC were retrieved by searching PubMed, Cochrane’s Library, and Embase databases. Presence of CAC was confirmed according to an Agatston’s Score >0 upon computed tomography examination. A random-effect model incorporating between-study heterogeneity was used to pool the results.ResultsSixteen studies involving 3,039 patients with psoriasis and 46,191 controls without psoriasis were included in the meta-analysis. All participants were without previously known cardiovascular diseases. Pooled results showed that psoriasis was associated with overall CAC [odds ratio (OR): 1.54, 95% confidence interval: 1.23–1.91, p < 0.001; I2 = 57%], after matching or adjusting the conventional cardiovascular risk factors. Subgroup analyses showed that study country, comorbidity of psoriatic arthritis, baseline Psoriasis Area and Severity Index, and duration of psoriasis (p for subgroup difference all >0.05) did not significantly affect the association of psoriasis and CAC. However, a stronger association was observed in younger patients (mean age <50 years, OR: 2.63, p < 0.001) compared to older patients (≥50 years, OR: 1.24, p = 0.02; p for subgroup difference <0.001).ConclusionPsoriasis is associated with CAC, and the association may be stronger in younger patients.