Pasteurella multocida serotype A (P. multocida) is frequently associated with severe respiratory disease in swine (Sus scrofa), highlighting the need for effective preventive strategies. To identify protective antigens suitable for a subunit vaccine targeting porcine P. multocida infection, six recombinant proteins (rAspA, rLolA, rOmpP6, rOppA, rRps6, rSmpA) were expressed in a prokaryotic system, and their efficacy was evaluated in a Mus musculus (Kunming) mouse model. All proteins were purified using His-tag affinity chromatography, and SDS-PAGE analysis confirmed expression with bands at the expected molecular weights (61, 26, 21, 63, 19, and 17 kDa). Each protein, formulated with ISA 201 adjuvant, was administered to mice in two immunizations. Indirect ELISA of sera collected at multiple time points demonstrated that all vaccines induced high antigen-specific IgG levels. rOppA, rLolA, rOmpP6, and rRps6 were expressed in soluble form, whereas rAspA and rSmpA formed inclusion bodies. In a lethal challenge model, rLolA and rRps6 conferred the highest protection (60% each), followed by rAspA and rOmpP6 (30%), rOppA (20%), and rSmpA (10%). Under the conditions tested, the highest protection observed was 60%, and none of the six antigens achieved complete protection against homologous A7 challenge in mice. This first head-to-head comparison under identical conditions provides a reference framework for future antigen screening studies.

S. suis is a major zoonotic infectious disease whose serological diversity brings challenges to vaccine development. Based on the whole-genome data of 169 S. suis strains, this study conducted a systematic bioinformatics analysis of the surface antigen protein HP0197 that reveals its distribution characteristics, sequence diversity, domain composition and antigenic epitope distribution. The results showed that the HP0197 gene, which has a detection rate of 91.72%, can be divided into seven major phylogroups (I-VII) and the following two structural types: short form (HP0197-S) and long form (HP0197-L). All sequences contained signal peptides, transmembrane structures, LPXTG anchoring motifs, as well as conserved GAGBD and G5 domains, among which tandem repeats of the G5 domain existed in the long HP0197-L type. Tertiary structure prediction indicated that HP0197 has a spatial architecture of "conserved at both ends and flexible in the middle", in which B-cell epitopes are mainly enriched near the GAGBD and G5 domains, suggesting these regions are the key targets for inducing cross-immune protection. It systematically elucidates the diversity and structural characteristics of the HP0197 protein from the perspective of population genetics, which provides a theoretical basis for optimizing existing subunit vaccines, designing broad-spectrum multi-epitope vaccines and exploring novel anti-infection strategies.

This study investigated the effects of chronic heat stress (HS) on brain injury in broilers and the associated molecular changes. A chronic HS model was established by exposing broilers to 35 °C from 08:00 to 20:00 daily from 21 to 42 days of age, and samples were collected at 28, 35, and 42 days of age. Chronic HS significantly impaired growth performance and was associated with histopathological and ultrastructural alterations in brain tissue. Serum antioxidant enzyme activities and the total antioxidant capacity were significantly reduced, whereas malondialdehyde levels were significantly increased, indicating sustained oxidative stress (OS). Blood–brain barrier (BBB) permeability, assessed by Evans blue extravasation, was significantly higher in HS birds and was accompanied by reduced mRNA expression of the tight junction-related genes ZO-1 and Claudin-5. In addition, chronic HS was associated with increased mRNA expression in genes related to cellular stress, oxidative stress, and inflammation, including key components of the TLR4/MyD88/NF-κB/NLRP3 pathway, as well as decreased expression of IL-4. These findings suggest that chronic HS is associated with enhanced OS, altered neuroinflammatory gene expression, and BBB impairment in the broiler brain. Overall, this study provides evidence that chronic HS is associated with brain injury in broilers and highlights a potential link among OS, inflammation-related transcriptional changes, and BBB dysfunction, thereby offering a basis for further mechanistic and interventional studies.

Local surveillance of molecular resistance to first-line anti-tuberculosis (TB) drugs and fluoroquinolones (FQs) was initiated in 2019, but existing reports remain limited, hindering effective TB prevention and control efforts. This study aims to investigate molecular resistance to first-line anti-TB drugs and FQs, assess risk factors for FQs resistance, and provide insights into the spread of drug-resistant tuberculosis (DR-TB) to inform more effective control and treatment strategies. Sputum samples from 25,150 non-duplicate patients attending 10 designated TB medical institutions across Luoyang City and all county and township areas under its jurisdiction from January 2019 to December 2023 were analyzed via fluorescence real-time PCR to detect Mycobacterium tuberculosis complex (MTBC)-positive strains. Multicolor melting curve analysis (MMCA) was performed on 4,131 non-repetitive MTBC strains to assess their molecular resistance to first-line anti-TB drugs and FQs. Risk factors for FQs resistance and the impact of first-line anti-TB drug resistance on FQs resistance were also assessed. Between 2019 and 2023, 4,131 MTBC strains were collected. Resistance to first-line anti-TB drugs was higher in males, retreated patients, individuals younger than 61 years, and those from the main urban area, compared to females, newly diagnosed patients, individuals over 60 years, and residents of county and township areas (59.1

Pasteurella multocida infects a wide range of animals, causing hemorrhagic septicemia or infectious pneumonia. Iron is an essential nutrient for growth, colonization, and proliferation of P. multocida during infection of the host, and competition for iron ions in the host is a critical link in the pathogenesis of this pathogen. In recent years, there has been significant progress in the study of the iron uptake system of P. multocida, including its occurrence and regulatory mechanisms. In order to provide a systematic theoretical basis for the study of the molecular pathogenesis of the P. multocida iron uptake system, and generate new ideas for the investigation and development of molecular-targeted drugs and subunit vaccines against P. multocida, the mechanisms of iron uptake by transferrin receptors, heme receptors, and siderophores, and the mechanism of expression and regulation of the P. multocida iron uptake system are all described.

Introduction:This study aimed to investigate the prevalence of resistance to first-line anti-tuberculosis (TB) drugs and the molecular mechanisms underlying resistance mutations in patients with culture-positive Mycobacterium tuberculosis complex (MTBC). The findings provide a data basis for developing more precise and regionally tailored anti-TB treatment regimens. Methods:From 2015 to 2022, a total of 3,605 strains isolated from 10 designated TB medical institutions in the main urban and county/township areas of Luoyang City, China, were confirmed as MTBC members through polymerase chain reaction (PCR) targeting a specific insertion sequence IS6110. Drug susceptibility testing using the proportional method was performed to analyze resistance patterns to first-line anti-TB drugs, namely, isoniazid (INH), rifampin (RFP), streptomycin (SM), and ethambutol (EMB). Molecular drug susceptibility testing was conducted on resistant strains using multicolor melting curve analysis (MMCA) to determine the mutation mechanisms associated with phenotypic resistance. Results:Among the 3,605 culture-positive MTBC cases, 79.5% (2,866 cases) were male, 64.9% (2,341 cases) resided in county and township areas, and 64.8% (2,336 cases) were younger than 60 years. The resistance rates for first-line anti-TB drugs, from highest to lowest, were SM (16.5%), INH (15.7%), RFP (9.9%), and EMB (6.4%). The overall TB resistance rates were significantly higher in the main urban areas. During the study period, the proportion of mono-resistance tuberculosis (MR-TB), multidrug-resistant tuberculosis (MDR-TB) and polydrug-resistant tuberculosis (PDR-TB) decreased by 59.2% (12.9-5.3%), 40.3% (12.4-7.4%), and 68.3% (6.9-2.2%), respectively. The predominant resistance patterns for MDR-TB and PDR-TB were MDR4 (INH + RIF + EMB + SM) and PDR2 (INH + SM). The significant molecular mutations observed were rpsL43 for SM resistance (66.2%, 344 cases), katG315 for INH resistance (70.6%, 361 cases), rpoB529-533 for RFP resistance (54.0%, 183 cases), and embB306 for EMB resistance (56.5%, 108 cases). Resistance in MDR-TB and PDR-TB cases frequently involved combinations of hotspot mutations but was not strictly confined to these sites. Conclusion:Tuberculosis resistance rates have declined over time, with distinct regional variations in resistance patterns. Significant molecular mutations responsible for drug resistance predominantly involve common hotspot mutations, but they are not limited to these.

The liver accounts for almost 95% of lipid metabolism in broilers and serves as a crucial metabolic organ. Stress, which occurs when broilers are exposed to a heated environment, inhibits liver metabolism, significantly impacting their growth. This experiment investigated the combination of GBE with TP to improve hepatic lipid metabolism in heat-stressed broiler chickens by inhibiting the AMPK/SREBP-1C/ACC pathway. Three hundred broilers were reared usually until 21 days and randomly divided into six groups, namely CON group, HS group, TP group (300 mg/kg), GBE100 group (GBE100 mg/kg + TP300 mg/kg), GBE300 group (GBE 300 mg/kg + TP 300 mg/kg), GBE600 (600 mg/kg + TP 300 mg/kg) groups, where the CON group was kept at 23 °C, and the HS group and the TP, GBE100, GBE300, and GBE600 groups of each medication group were kept at 35 ± 2 °C for 10 h per day. Liver and serum samples were extracted at 28 and 42 days of age, respectively. The results showed that, at 42 days of age, the GBE600 group exhibited significantly superior performance to the HS group in ADG, ADFI, and F/G (p < 0.01). Serum TG, TC, and LDL-C levels were significantly lower (p < 0.01), while HDL-C levels were significantly higher (p < 0.05). Additionally, the mRNA expression levels of LKB1, AMPK, SREBP-1C, and ACC were markedly reduced (p < 0.01). In contrast, the mRNA expression of HSL and CPT1A was significantly elevated (p < 0.01), indicating that the GBE600 was more effective in mitigating heat stress in broiler chickens at 42 days of age. It showed that the GBE600 was more effective in ameliorating heat stress in broilers at 42 days of age, thus providing an ethical basis for ameliorating the flocculation of hepatic lipid metabolism in heat-stressed broilers.

Purpose:Existing data offer limited guidance on TB control strategies for the non-elderly population, hampering effective epidemic management. This study aimed to analyze TB transmission and molecular resistance profiles among non-elderly patients (<60 years) in Luoyang City. Patients and Methods:From 2019-2023, 24,706 non-duplicate sputum samples from 10 TB-designated hospitals were tested for Mycobacterium tuberculosis complex (MTBC) via IS6110-targeted real-time PCR. MTBC-positive specimens underwent multicolor melting curve analysis (MMCA) to assess resistance to isoniazid (INH), rifampin (RFP), streptomycin (SM), and ethambutol (EMB). Age-stratified analyses were performed to compare drug-resistant TB (DR-TB) prevalence between elderly and non-elderly groups, with multivariate regression identifying resistance risk factors in non-elderly patients. Results:Non-elderly individuals exhibited significantly higher TB (17.54% vs 15.26%) and DR-TB (26.82% vs 21.62%) rates than the elderly (all, P < 0.001). Among non-elderly patients, males, retreatment cases, main urban residents and smear-positive groups had significantly elevated MTBC detection rates. The predominant resistance patterns of multidrug-resistant tuberculosis (MDR-TB) and poly-resistant tuberculosis (PDR-TB) were MDR4 (INH + RFP + EMB + SM) and PDR2 (INH + SM), with detection rates of 5.52% (142) and 2.33% (60), respectively. MTBC positive rate peaked at 30-34 years (23.10%), while the resistance rate peaked at 35-39 years. After adjusting for the effects of smear results and diagnosis year, the multivariate regression analysis model indicated that male sex, retreatment, and the main urban area were high-risk factors for TB resistance in non-elderly cases. Conclusion:The non-elderly population demonstrates a significantly higher burden of both TB detection and resistance, particularly among males, retreatment cases, and main urban patients. The emergence of complex drug resistance patterns, combined with a distinct trend of younger age at infection, highlights the critical need for targeted interventions tailored to specific epidemiological and resistance profiles of MTBC-infected populations.

Pasteurella multocida is capable of infecting various animal species, causing hemorrhagic septicemia or infectious pneumonia, and it is widely prevalent and pathogenic worldwide. However, the prevention and control technologies for animal pasteurellosis remain relatively under-developed, with a heavy reliance on the traditional inactivated vaccines and live attenuated vaccines developed in the mid-20th century. A previous systematic review summarized research progress in the field of inactivated vaccines for animal pasteurellosis and revealed that inactivated vaccines exhibit high levels of homologous protective efficacy, albeit with a relatively short duration of immunity and limited cross-protection between different serotypes. Live attenuated vaccines are known to exhibit significant advantages, including a prolonged duration of immunity, strong cross-protective capacity, and low production costs. Throughout the history of vaccine development, various live attenuated vaccines have been extensively used as critical tools for preventing and controlling infectious diseases in animals and humans and combating antimicrobial resistance, substantially reducing the morbidity and mortality rates of regional or international epidemics. The developmental history of live attenuated vaccines against Pasteurella multocida has primarily encompassed three distinct research and application periods, characterized by natural attenuated vaccines, traditional attenuated vaccines, and genetically engineered live attenuated vaccines. Here, we comprehensively review the research and application history of natural attenuated vaccines for Pasteurella multocida. Our aim was to provide theoretical foundations and novel perspectives for the development of a new generation of live attenuated vaccines against pasteurellosis in livestock and poultry.

Abstract Background High-temperature environment can cause acute kidney injury affecting renal filtration function. To study the mechanism of renal injury caused by heat stress through activates TLR4/NF-κB/NLRP3 signaling pathway by disrupting the filtration barrier in broiler chickens. The temperature of broilers in the TN group was maintained at 23 ± 1 °C, and the HS group temperature was maintained at 35 ± 1℃ from the age of 21 days, and the high temperature was 10 h per day, and one broiler from each replicate group at the age of 35 and 42 days was selected for blood sampling, respectively. Results The ELISA results demonstrated that in comparison to the TN group, serum CORT content of broilers in the HS group was all remarkably elevated (P < 0.01); the levels of IL-6 and TNF-α in the serum were remarkably elevated (P < 0.05 or P < 0.01); serum CAT and SOD activities were all remarkably reduced (P < 0.05 or P < 0.01), and serum LDH activity and MDA content were all remarkably decreased (P < 0.05); serum BUN and CRE levels were remarkably elevated (P < 0.01). Pathological sections and transmission electron microscopy demonstrated that the structure of the renal filtration barrier in the HS group damaged gradually with the prolongation of heat stress in comparison to the TN group, but the damage was reduced at 42 days of age; the levels of TLR4, MyD88, NF-κB, NF-κB-p65, NLRP3, caspase-1 and IL-1β mRNAs were all up-regulated (P < 0.05 or P < 0.01) in renal tissues of the HS group, indicating that heat stress caused damage to the morphological structure and function of the renal filtration barrier and that TLR4/NF-κB/NLRP3 pathway was also affected by heat stress, leading to increased activity (P < 0.05 or P < 0.01). Conclusions It demonstrated that heat stress caused detrimental effects on both the morphological structure and function of the renal filtration barrier, and the initiation of the TLR4/NF-κB/NLRP3 signaling pathway exacerbated the inflammatory damage, leading to increased thermal damage to renal tissues and glomerular filtration barriers; however, with the prolongation of heat stress, broilers gradually developed heat tolerance, and the damage to the renal tissues and filtration barriers triggered by heat stress was mitigated.

BACKGROUND:Tuberculosis (TB) remains a global public health event of great concern, however epidemic data on TB covering entire areas during the special period of the COVID-19 epidemic have rarely been reported. We compared the dissemination and multidrug-resistance patterns of Mycobacterium tuberculosis complex (MTBC) in the main urban area of Luoyang City, China (including six municipal jurisdictions) and nine county and township areas under its jurisdiction, aimed to establish the epidemiology of TB in this region and to provide reference for precision anti-TB in places with similar settings. METHODS:From 2020 to 2022, sputum samples were collected from 18,504 patients with confirmed, suspected and unexcluded TB in 10 designated TB medical institutions. Insertion sequence 6110 was amplified by PCR (rpoB gene detection if necessary) to confirm the presence of MTBC. PCR-positive specimens were analyzed by multicolor melting curve analysis to detect multidrug resistance. RESULTS:Among the 18,504 specimens, 2675 (14.5%) were MTBC positive. The positive rate was higher in the main urban area than in the county and township areas (29.8% vs. 10.9%, p < 0.001). Male, re-treated and smear-positive groups were high-burden carriers of MTBC. Individuals aged > 60 years were the largest group infected with MTBC in the main urban area, compared with individuals aged < 61 years in the county and township areas. The detection of multidrug-resistant TB (MDR-TB) was higher in the main urban area than in the county and township areas (13.9% vs. 7.8%, p < 0.001). In all areas, MDR-TB groups were dominated by males, patients with a history of TB treatment, and patients aged < 61 years. Stratified analysis of MDR-TB epidemiology showed that MDR4 (INH þ RIF þ EMB þ SM) was predominant in the main urban area, while MDR3 (INH þ RIF þ SM) was predominant in the county and township areas. MDR-TB detection rate and epidemiology differed among the county and township areas. CONCLUSIONS:For local TB control, it is necessary to plan more appropriate and accurate prevention and control strategies according to the regional distribution of MTBC infection.

AbstractGlaesserella parasuis (GPS) is an important bacterial pathogen of swine. Serotype identification has presented a bottleneck in GPS research since it was first identified as the pathogen causing Glässer’s disease in pigs in 1910. This paper presents a systematic review of the history of the development and application of gel immunodiffusion (GID), indirect hemagglutination assay (IHA), and polymerase chain reaction (PCR) typing methods for GPS, and the discovery of their shared antigenic basis. It provides a systematic theoretical overview of the immunology and principles underlying the three typing methods and offers new ideas for research into the prevention and control of Glässer’s disease. In 1992, GPS was first classified into serotypes 1–15 using GID based on GPS heat-stable antigens, but about 25% of the strains were found to be non-typeable, and the composition of their antigens for serotyping was unclear. In 2003, the IHA method was established based on saline-extracted antigens of GPS, whose sensitivity and typing rate were higher than for GID, although about 15% of strains were still found to be non-typeable. The results of IHA and GID typing are roughly consistent, since they share the same GPS surface polysaccharide serotyping antigens, although whether these are capsular polysaccharides, lipopolysaccharides, or other polysaccharides, remains to be determined. In 2013, the Capsular polysaccharide (CPS) synthetic gene clusters from GPS serotypes 1–15 were successfully analyzed, confirming that CPS is essential for the formation of antigens for serotyping. In 2015, primers were designed based on the specific target genes of GPS capsules to establish a PCR typing method (H-PCR) for GPS, which, however, could not identify serotypes 5 and 12. In 2017, a new PCR typing method (J-PCR) was established based on the specific target genes of GPS capsules, which could identify serotypes 5 and 12. A combination of the two PCR typing methods enables the typing of almost all GPS strains, and the consistency with GID and IHA was verified using molecular biological methods. The antigenic basis of the three typing methods was shown to involve the GPS capsule. PCR typing methods are characterized by simple operation, fast speed, and low cost, and can successfully solve many problems in GID and IHA serotyping, and so have become widely adopted.

The spleen is the largest peripheral immune organ of the organism, accounting for 25% of the total lymphoid tissue of the body. During HS, the spleen is damaged due to the elevated environment, which seriously affects life performance and broilers’ health. This study aimed to investigate the mechanism of chronic HS damage to broiler spleen tissues. The broilers were typically raised until they reached 21 days of age, after which they were arbitrarily allocated into two groups: an HS group and a cntrol group. The HS group was subjected to a temperature of 35 °C for 10 h each day, starting at 21 days of age. At 35 and 42 days of age, spleen and serum samples were obtained from the broilers. The results showed that after HS, a significant decrease in productive performance was observed at 42 days of age (p < 0.01), and the spleen index, and bursa index were significantly decreased (p < 0.01). T-AOC of the organism was significantly decreased (p < 0.05), GSH-PX, SOD, and CAT antioxidant factors were significantly decreased (p < 0.01), and MDA was significantly elevated (p < 0.01). HS also led to a significant increase in cytokines IL-6, TNF-α, and INF-γ and a significant decrease in IL-4 in the spleen. The histopathologic results showed that the spleen’s red-white medulla was poorly demarcated. The cells were sparsely arranged after HS. After HS, the expression of TLRs, MYD88, and NF-κB genes increased significantly. The expression of HSP70 increased significantly, suggesting that HS may induces an inflammatory response in broiler spleens through this signaling pathway, which may cause pathological damage to broiler spleens, leading to a decrease in immune function and progressively aggravating HS-induced damage with the prolongation of HS.

为分析临床分离的52株猪源支气管败血波氏杆菌(Bb)在纸片扩散法(K-B)药敏试验中出现的庆大霉素(GEN)异质性耐药(HR)情况,本研究采用微量肉汤稀释法检测52株Bb分离株对GEN的最小抑菌浓度(MIC);采用K-B法检测分离株对GEN的敏感性;通过观察抑菌环内是否有菌落初步筛选疑似GEN HR菌株;采用菌落谱性分析法(PAP)测定初筛菌株的MIC与最大不抑菌浓度(MNIC)的比值,以及耐药亚群菌株的发生频率,验证初筛的HR菌株.结果显示:52株猪源Bb对GEN耐药的菌株占13.46%(7/52),多数分离株的MIC值为2 μg/mL～8 μg/mL,对GEN表现为敏感或中介,占全部菌株的86.54%(45/52),其中Bb48株的MIC为2 μg/mL,抑菌环直径为16 mm属于GEN敏感菌株.通过观察纸片法药敏试验中的抑菌环内是否存在菌落,初步筛选对GEN HR的菌株.结果显示,有7株疑似HR菌株;PAP试验结果显示,6株疑似HR菌株的MIC/MNIC比值均小于8,为假阳性HR菌株,只有Bb48株的MIC/MNIC值为16且耐药亚群发生频率为1.3×10-6,按照标准判定其为GEN HR Bb菌株.从PAP 试验验证的Bb48株中有菌落生长的最高浓度GEN平板上随机挑3株耐药亚群菌株,37℃培养12 h,每小时测一次菌落数,共测12 h连同Bb48株一起绘制生长曲线;将上述试验选取的3株耐药亚群菌株连续传50代,每5代测其MIC值判定耐药亚群菌株的耐药遗传稳定性.生长曲线结果显示Bb48株及其耐药亚群菌株的生长速率均无显著差异(P＞0.05);耐药遗传稳定性试验结果显示,将Bb48株中的3株耐药亚群菌株传代,其中两株菌各代次的MIC均为32 μg/mL,1株菌的MIC为8 μg/mL～32 μg/mL.表明耐药亚群菌株对GEN的耐药性能够有效遗传.上述结果表明,52株猪源Bb中的Bb48为GEN HR菌株,Bb48及其耐药亚群菌株的生长速率基本一致,且对GEN的耐药性能够稳定遗传.本研究首次得到了罕见的对GEN HR的Bb菌株,提示临床中应合理使用GEN,并监测HR菌株的出现,对临床使用GEN治疗猪源Bb感染具有重要指导意义.

IntroductionPasteurella multocida is a widespread respiratory pathogen in pigs, causing swine pneumonia and atrophic rhinitis, and the capsular serogroups A and D are the main epidemic serogroups in infected animals. This study investigated the protective effects of serogroup A and D bacterins against current circulating P. multocida strains, to better understand the immunity generated by bacterins. Method13 serogroup A (seven A: L3 and six A: L6 strains) and 13 serogroup D (all D: L6 strains) P. multocida strains were isolated, and used as inactivated whole cell antigen to prepare P. multocida bacterins. Mice were immunized with these bacterins at 21-day interval and intraperitoneally challenged with the homologous and heterologous P. multocida strains, respectively. The antibody titer levels and immunization protective efficacy of vaccines were evaluated. ResultsAll of the bacterins tested induced high titer levels of immunoglobulin G antibodies against the parental bacterial antigen in mice. Vaccination with the six A: L6 bacterins provided no protection against the parent strain, but some strains did provide heterologous protection against A: L3 strains. Vaccination with the seven A: L3 bacterins provided 50%-100% protection against the parent strain, but none gave heterologous protection against the A:L6 strains. Immunization with the thirteen D: L6 bacterins offered 60%-100% protection against the parent strain, and almost all D: L6 strains gave cross-protection. DiscussionThis study found that the cross-protectivity of serogroup A strains was poor, while serogroup D strains was effective, which provided some insights for P. multocida vaccine development.

As an important respiratory organ, the lung is susceptible to damage during heat stress due to the accelerated breathing frequency caused by an increase in environmental temperature. This can affect the growth performance of animals and endanger their health. This study aimed to explore the mechanism of lung tissue damage caused by heat stress. Broilers were randomly divided into a control group (Control) and a heat stress group (HS). The HS group was exposed to 35°C heat stress for 12 h per d from 21-days old, and samples were taken from selected broilers at 28, 35, and 42-days old. The results showed a significant increase in lactate dehydrogenase (LDH) activity in the serum and myeloperoxidase (MPO) activity in the lungs of broiler chickens across all 3 age groups after heat stress (P < 0.01), while the total antioxidant capacity (T-AOC) was significantly enhanced at 35-days old (P < 0.01). Heat stress also led to significant increases in various proinflammatory factors in serum and expression levels of HSP60 and HSP70 in lung tissue. Histopathological results showed congestion and bleeding in lung blood vessels, shedding of pulmonary epithelial cells, and a large amount of inflammatory infiltration in the lungs after heat stress. The mRNA expression of TLRs/NF-κB-related genes showed an upward trend (P < 0.05) after heat stress, while the mRNA expression of MLCK, a gene related to pulmonary blood-air barrier, significantly increased after heat stress, and the expression levels of MLC, ZO-1, and occludin decreased in contrast. This change was also confirmed by Western blotting, indicating that the pulmonary blood-air barrier is damaged after heat stress. Heat stress can cause damage to the lung tissue of broiler chickens by disrupting the integrity of the blood-air barrier and increasing permeability. This effect is further augmented by the activation of TLRs/NF-κB signaling pathways leading to an intensified inflammatory response. As heat stress duration progresses, broiler chickens develop thermotolerance, which gradually mitigates the damaging effects induced by heat stress.

To evaluate the molybdenum (Mo)-induced changes of intestinal morphology and the relationship of intestinal tight junction (TJ) proteins expression and intestinal barrier function, a total of 20 healthy sheep were randomly divided into five groups of four: 0, 5, 10, 20, and 50 mg/kg BW/day Na 2 MoO 4 ·2H 2 O were administrated in five groups named control group, Mo 5 group, Mo 10 group, Mo 20 group, and Mo 50 group, respectively. After 28 days of Mo treatment, the duodenum, the jejunum, and the ileum tissue were collected. The histopathology and the developmental parameters were evaluated by hematoxylin–eosin staining. The intestinal epithelial cell DNA damage was detected by TdT-mediated dUTP nick end labeling assay. The intestinal glycoprotein and the goblet cells were analyzed by Alcian Blue-Periodic Acid-Schiff (AB-PAS) staining and PAS staining, respectively. TJ proteins were determined by immunofluorescence technology. Results showed that excessive Mo significantly decreased the small intestinal villus height (VH), crypt depth (CD), VH/CD, and mucosal thickness ( P < 0.05 or P < 0.01) while induced the damage of DNA in small intestinal epithelial cells. Moreover, excessive Mo injured intestinal barrier function by decreasing the percent of glycoprotein distribution area ( P < 0.05) and the relative density of intestinal goblet cells ( P < 0.05). Mo treatment induced decreased ( P < 0.01) expression of Zonula Occludens-1, Occludin, and Claudin-1. In conclusion, excessive Mo interfered with the expression of TJ proteins, inhibited intestinal epithelial development, and further aggravated the intestinal barrier function damage, leading to disturbing the small intestinal microenvironment balance.

目的 研究洛阳市和县区结核分枝杆菌链霉素与乙胺丁醇耐药模式,指导临床用药,补充当地耐药结核的流行病学数据.方法 该研究共纳入 2 941 例高分辨率熔解曲线(HRM)的阳性结果,评估与链霉素和乙胺丁醇耐药相关的危险因素.结果 在被纳入的 2 941 例 HRM 阳性病例中,18.4%对链霉素耐药,8.0%对乙胺丁醇耐药,男性对链霉素和乙胺丁醇耐药率均高于女性(19.0%vs 16.9%,P = 0.129;8.0%vs 7.9%,P = 0.987),城市群体高于乡村(21.3%vs 16.6%,P =0.002;9.8%vs 6.9%,P =0.004),复诊群体远高于初诊患者(25.8%vs 17.3%,P<0.001;12.1%vs 7.4%,P =0.002),年龄<51 岁群体链霉素耐药率高于年龄>50 岁的群体(21.1%vs 16.1%,P<0.001).按年龄分层,链霉素及乙胺丁醇最高耐药率,男性分别出现在31～35 岁和 56～60 岁,而女性则分别出现在 21～25 岁及56～60 岁.多变量模型中,在调整了涂片结果和年份检测后,既往治疗史、年龄<51 岁、城镇地区与链霉素和乙胺丁醇耐药性呈正相关.结论 该地区男性、既往治疗史、年龄<51 岁和城镇居住群体是链霉素与乙胺丁醇耐药结核的重点监测目标.

ObjectiveWe aimed to examine the prevalence of multidrug-resistant tuberculosis (MDR-TB) in Luoyang, China, identify related risk factors, inform clinical practices, and establish standardized anti-tubercular treatment regimens. MethodsWe conducted a retrospective analysis of high-resolution melting curve (HRM) data from 17,773 cases (2,748 of which were positive) between June 2019 and May 2022 to assess the prevalence of MDR-TB and to identify its associated risk factors. ResultsBetween June 2019 and May 2022, out of the 17,773 HRM results, 2,748 were HRM-positive, and 312 were MDR-TB cases. The detection rates for HRM-positive and MDR-TB were 17.0 and 12.1% for males, and 12.4 and 8.2% for females, respectively. The MDR-TB detection rate was higher in the urban areas (14.6%) than in the rural areas (10.6%) and more common among individuals under 51 years of age (14.1%) than those over 50 years of age (9.3%). Notably, the rate of detecting MDR-TB was 18.3% higher in new male patients than in new female patients, which was at 10.6%, and this difference was statistically significant (p < 0.001). Moreover, the rate of MDR detection in females who had received anti-tuberculosis treatment (21.3%) was higher than that in males (16.9%). In the multivariate model that considered the results of the sputum smear and detection time, MDR-TB was positively correlated with a history of tuberculosis (TB) treatment, being male, being younger than 51 years, and living in urban areas. ConclusionLocal TB infections are complex and diverse; therefore, more comprehensive monitoring methods are needed to curb the spread of MDR-TB.