Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus. / 人脐带间å 质干细胞通过IGF1R-CHK2-p53信号轴减轻2åž‹ç³–å°¿ç— é›„æ€§å¤§é¼ ç³–å°¿ç— è‚¾ç— .

Diabetes mellitus (DM) is a disease syndrome characterized by chronic hyperglycaemia. A long-term high-glucose environment leads to reactive oxygen species (ROS) production and nuclear DNA damage. Human umbilical cord mesenchymal stem cell (HUcMSC) infusion induces significant antidiabetic effects in type 2 diabetes mellitus (T2DM) rats. Insulin-like growth factor 1 (IGF1) receptor (IGF1R) is important in promoting glucose metabolism in diabetes; however, the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear. In this study, a DM rat model was induced with high-fat diet feeding and streptozotocin (STZ) administration and rats were infused four times with HUcMSC. Blood glucose, interleukin-6 (IL-6), IL-10, glomerular basement membrane, and renal function were examined. Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays. The expression of IGF1R, phosphorylated checkpoint kinase 2 (p-CHK2), and phosphorylated protein 53 (p-p53) was examined using immunohistochemistry (IHC) and western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of 8-hydroxydeoxyguanosine (8-OHdG). Flow cytometry experiments were used to detect the surface markers of HUcMSC. The identification of the morphology and phenotype of HUcMSC was performed by way of oil red "O" staining and Alizarin red staining. DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane, increased the expression of IGF1 and IGF1R. IGF1R interacted with CHK2, and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells. When cisplatin was used to induce DNA damage, the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment. HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats. The expression of IGF1, IGF1R, p-CHK2, and p-p53, and the level of 8-OHdG in the DM group increased significantly compared with those in the control group, and decreased after HUcMSC treatment. Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage. HUcMSC infusion protected against kidney injury in DM rats. The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus. / 人脐带间å 质干细胞通过IGF1R-CHK2-p53信号轴减轻2åž‹ç³–å°¿ç— é›„æ€§å¤§é¼ ç³–å°¿ç— è‚¾ç— .

Diabetes mellitus (DM) is a disease syndrome characterized by chronic hyperglycaemia. A long-term high-glucose environment leads to reactive oxygen species (ROS) production and nuclear DNA damage. Human umbilical cord mesenchymal stem cell (HUcMSC) infusion induces significant antidiabetic effects in type 2 diabetes mellitus (T2DM) rats. Insulin-like growth factor 1 (IGF1) receptor (IGF1R) is important in promoting glucose metabolism in diabetes; however, the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear. In this study, a DM rat model was induced with high-fat diet feeding and streptozotocin (STZ) administration and rats were infused four times with HUcMSC. Blood glucose, interleukin-6 (IL-6), IL-10, glomerular basement membrane, and renal function were examined. Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays. The expression of IGF1R, phosphorylated checkpoint kinase 2 (p-CHK2), and phosphorylated protein 53 (p-p53) was examined using immunohistochemistry (IHC) and western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of 8-hydroxydeoxyguanosine (8-OHdG). Flow cytometry experiments were used to detect the surface markers of HUcMSC. The identification of the morphology and phenotype of HUcMSC was performed by way of oil red "O" staining and Alizarin red staining. DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane, increased the expression of IGF1 and IGF1R. IGF1R interacted with CHK2, and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells. When cisplatin was used to induce DNA damage, the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment. HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats. The expression of IGF1, IGF1R, p-CHK2, and p-p53, and the level of 8-OHdG in the DM group increased significantly compared with those in the control group, and decreased after HUcMSC treatment. Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage. HUcMSC infusion protected against kidney injury in DM rats. The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Polylactic acid microplastics cause transgenerational reproductive toxicity associated with activation of insulin and hedgehog ligands in C. elegans.

As a member of biodegradable plastics, exposure risk of polylactic acid microplastic (PLA-MP) has received attention recently. Toxicity of PLA-MP at parental generation (P0-G) has been observed in some organisms; however, its possible transgenerational toxicity and underlying mechanisms remain unclear. In Caenorhabditis elegans, 10 and 100 µg/L PLA-MP resulted in transgenerational inhibition in reproductive capacity and transgenerational damage on gonad development. Meanwhile, transgenerational increase in germline apoptosis was detected after PLA-MP exposure at P0-G, which was associated with transgenerational dysregulation in expressions of genes governing apoptosis (ced-3, ced-4, egl-1, and ced-9) and DNA damage related genes (cep-1, mrt-2, hus-1, and clk-2). Among secreted ligand genes, PLA-MP exposure induced transgenerational increase in expression of ins-39 and wrt-3, and RNAi of ins-39 and wrt-3 inhibited germline apoptosis in PLA-MP exposed nematodes. Additionally, PLA-MP caused transgenerational increase in expression of met-2 and set-6 encoding histone methylation transferases, and germline apoptosis induced by PLA-MP could be suppressed by RNAi of met-2 and set-6. Dysregulated expressions of some apoptosis and DNA damage related genes caused by PLA-MP were reversed by RNAi of ins-39, wrt-3, met-2, and set-6. Moreover, in PLA-MP exposed animals, expression of ins-39 and wrt-3 could be further inhibited by RNAi of met-2 and set-6. Therefore, PLA-MP potentially induced reproductive toxicity across multiple generations, which was under the control of MET-2 and SET-6 activated ligands of INS-39 and WRT-3.

Efficient extraction of nickel from chloride system using a cleaner extractant: Taking the example of processing nickel-aluminum slag remaining from spent hydroprocessing catalysts.

The efficient recovery of nickel from chloride systems has long presented a challenge in the field. While solvent extraction is a viable approach, conventional extractants have been associated with drawbacks such as a high requirement for chloride ions and substantial consumption of acids and alkalis. In response to these challenges, this investigation developed and synthesized a novel thiazole-based extractant, N, N-Bis(4-thiazolylmethyl)octylamine (NNBT), tailored for the selective extraction of nickel from chloride systems. Findings from the study indicate that the nitrogen atom situated on the benzylamine framework within NNBT can interact synergistically with the chelating thiazole ring, facilitating effective nickel extraction and notably reducing the need for chloride ions. Furthermore, the extractant can be regenerated using deionized water, thereby obviating the necessity for additional consumption of acids and alkalis. Following the validation of NNBT as an environmentally sustainable and efficient nickel extractant within the chloride ion system, it was successfully employed to selectively and effectively extract nickel from the nickel-aluminum slag of spent HDP catalyst. The extracted nickel and aluminum were subsequently processed into electroplated nickel chloride and polyaluminum chloride, respectively, meeting the national standards of China. These outcomes underscore the eco-friendliness and promise of NNBT for nickel extraction from chloride systems.

USP25 Elevates SHLD2-Mediated DNA Double-Strand Break Repair and Regulates Chemoresponse in Cancer.

DNA damage plays a significant role in the tumorigenesis and progression of the disease. Abnormal DNA repair affects the therapy and prognosis of cancer. In this study, it is demonstrated that the deubiquitinase USP25 promotes non-homologous end joining (NHEJ), which in turn contributes to chemoresistance in cancer. It is shown that USP25 deubiquitinates SHLD2 at the K64 site, which enhances its binding with REV7 and promotes NHEJ. Furthermore, USP25 deficiency impairs NHEJ-mediated DNA repair and reduces class switch recombination (CSR) in USP25-deficient mice. USP25 is overexpressed in a subset of colon cancers. Depletion of USP25 sensitizes colon cancer cells to IR, 5-Fu, and cisplatin. TRIM25 is also identified, an E3 ligase, as the enzyme responsible for degrading USP25. Downregulation of TRIM25 leads to an increase in USP25 levels, which in turn induces chemoresistance in colon cancer cells. Finally, a peptide that disrupts the USP25-SHLD2 interaction is successfully identified, impairing NHEJ and increasing sensitivity to chemotherapy in PDX model. Overall, these findings reveal USP25 as a critical effector of SHLD2 in regulating the NHEJ repair pathway and suggest its potential as a therapeutic target for cancer therapy.

Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Leprosy: treatment, prevention, immune response and gene function.

Since the leprosy cases have fallen dramatically, the incidence of leprosy has remained stable over the past years, indicating that multidrug therapy seems unable to eradicate leprosy. More seriously, the emergence of rifampicin-resistant strains also affects the effectiveness of treatment. Immunoprophylaxis was mainly carried out through vaccination with the BCG but also included vaccines such as LepVax and MiP. Meanwhile, it is well known that the infection and pathogenesis largely depend on the host's genetic background and immunity, with the onset of the disease being genetically regulated. The immune process heavily influences the clinical course of the disease. However, the impact of immune processes and genetic regulation of leprosy on pathogenesis and immunological levels is largely unknown. Therefore, we summarize the latest research progress in leprosy treatment, prevention, immunity and gene function. The comprehensive research in these areas will help elucidate the pathogenesis of leprosy and provide a basis for developing leprosy elimination strategies.

Comparison of the immune effects of the Chlamydia abortus MOMP antigen displayed in different parts of bacterial ghosts.

Bacterial ghosts (BGs) are promising vaccine platforms owing to their high adjuvant properties and delivery efficiency. Heterologous antigens can be anchored to different parts of BGs using genetic engineering strategies to prepare vaccines. However, several key issues need to be resolved, including the efficient preparation of BGs and determining the optimal anchoring position of exogenous antigens in the BGs. Here, we prepared an efficient temperature-controlled lysis system using lysis gene E of phage PhiX174 and used the major outer membrane protein (MOMP) of Chlamydia abortus (C. abortus) as a model antigen to explore the optimal display location of exogenous antigens in BGs. We demonstrated that the constructed recombinant temperature-controlled lysis plasmid can still stably inhibit E gene expression at 37°C, and the lysis efficiency of E. coli can reach above 99.9%. Four recombinant MOMP Escherichia coli (E. coli) ghost vaccines were constructed using different anchor sequences. These vaccines all induced strong specific antibody responses and secrete high levels of IFN-γ in immunized mice and significantly increased the clearance of C. abortus in a mouse infection model. Notably, the strongest immune effect was observed when MOMP was displayed on the surface of E. coli ghosts (rECG-InpN-M), which resulted in the clearance of C. abortus in mice 6 days earlier than that with the recombinant MOMP vaccine. Altogether, we constructed an efficient BG temperature-controlled lysis system and provided a feasible strategy for developing a BG delivery platform with enhanced immune effects.

Isolation of Epizootic Hemorrhagic Disease Virus Serotype 10 from Culicoides tainanus and Associated Infections in Livestock in Yunnan, China.

Two strains of viruses, JC13C644 and JC13C673, were isolated from Culicoides tainanus collected in Jiangcheng County, Yunnan Province, situated along the border area shared by China, Laos, and Vietnam. JC13C644 and JC13C673 viruses can cause cytopathic effect (CPE) in mammalian cells BHK21 and Vero cells, and cause morbidity and mortality in suckling mice 48 h after intracerebral inoculation. Whole-genome sequencing was performed, yielding complete sequences for all 10 segments from Seg-1 (3942nt) to Seg-10 (810nt). Phylogenetic analysis of the sub-core-shell (T2) showed that the JC13C644 and JC13C673 viruses clustered with the Epizootic Hemorrhagic Disease Virus (EHDV) isolated from Japan and Australia, with nucleotide and amino acid homology of 93.1% to 98.3% and 99.2% to 99.6%, respectively, suggesting that they were Eastern group EHDV. The phylogenetic analysis of outer capsid protein (OC1) and outer capsid protein (OC2) showed that the JC13C644 and JC13C673 viruses were clustered with the EHDV-10 isolated from Japan in 1998, with the nucleotide homology of 98.3% and 98.5%, and the amino acid homology of 99.6% and 99.6-99.8%, respectively, indicating that they belong to the EHDV-10. Seroepidemiological survey results demonstrated that JC13C644 virus-neutralizing antibodies were present in 29.02% (177/610) of locally collected cattle serum and 11.32% (89/786) of goat serum, implying the virus's presence in Jiangcheng, Yunnan Province. This finding suggests that EHDV-10 circulates not only among blood-sucking insects in nature but also infects local domestic animals in China. Notably, this marks the first-ever isolation of the virus in China and its discovery outside of Japan since its initial isolation from Japanese cattle. In light of these results, it is evident that EHDV Serotype 10 exists beyond Japan, notably in the natural vectors of southern Eurasia, with the capacity to infect local cattle and goats. Therefore, it is imperative to intensify the surveillance of EHDV infection in domestic animals, particularly focusing on the detection and monitoring of new virus serotypes that may emerge in the region and pose risks to animal health.

The effect of modifier and a water-soluble fertilizer on two forages grown in saline-alkaline soil.

Saline-alkali soil significantly impairs crop growth. This research employs the impacts of the modifier and water-soluble fertilizer, as well as their interaction, on the root systems of alfalfa and leymus chinensis in saline-alkali soil. The results exhibit that the hydrochar source modifier effectively enhances the root growth of both forage species. There are certain improvements in the root growth indicators of both crops at a dosage of 20 g/kg. Root enzyme activity and rhizosphere soil enzyme activity are enhanced in alfalfa, showing significant improvements in the first planting compared to the second planting. The application of water-soluble fertilizers also promotes root growth and root dehydrogenase activity. The root dehydrogenase activity of alfalfa and leymus chinensis are enhanced 62.18% and 10.15% in first planting than that of blank, respectively. Additionally, the two-factor variance analysis revealed a correlation between rhizosphere soil enzyme activity and changes in root traits. Higher rhizosphere soil enzyme activity is observed in conjunction with better root growth. The combined application of a modifier and water-soluble fertilizer has demonstrated a significant interaction effect on various aspects of the first planting of alfalfa and leymus chinensis. Moreover, the combined application of the modifier and water-soluble fertilizer has yielded superior results when compared to the individual application of either the modifier or the water-soluble fertilizer alone. This combined approach has proven effective in improving saline-alkali soil conditions and promoting crop growth in such challenging environments.

Cellular nucleus image-based smarter microscope system for single cell analysis.

Cell imaging technology is undoubtedly a powerful tool for studying single-cell heterogeneity due to its non-invasive and visual advantages. It covers microscope hardware, software, and image analysis techniques, which are hindered by low throughput owing to abundant hands-on time and expertise. Herein, a cellular nucleus image-based smarter microscope system for single-cell analysis is reported to achieve high-throughput analysis and high-content detection of cells. By combining the hardware of an automatic fluorescence microscope and multi-object recognition/acquisition software, we have achieved more advanced process automation with the assistance of Robotic Process Automation (RPA), which realizes a high-throughput collection of single-cell images. Automated acquisition of single-cell images has benefits beyond ease and throughout and can lead to uniform standard and higher quality images. We further constructed a single-cell image database-based convolutional neural network (Efficient Convolutional Neural Network, E-CNN) exceeding 20618 single-cell nucleus images. Computational analysis of large and complex data sets enhances the content and efficiency of single-cell analysis with the assistance of Artificial Intelligence (AI), which breaks through the super-resolution microscope's hardware limitation, such as specialized light sources with specific wavelengths, advanced optical components, and high-performance graphics cards. Our system can identify single-cell nucleus images that cannot be artificially distinguished with an accuracy of 95.3%. Overall, we build an ordinary microscope into a high-throughput analysis and high-content smarter microscope system, making it a candidate tool for Imaging cytology.

Effect of maternal oxygen supplementation for parturient undergoing elective cesarean section by high-flow nasal oxygen compared with room air on fetal acidemia: study protocol for a randomized controlled trial.

BACKGROUND: Maternal oxygen supplementation is usually used as an intrauterine resuscitation technique to prevent fetal hypoxia and acidemia during delivery. However, there has been a great deal of controversy regarding the effects of prophylactic maternal oxygen during cesarean section, during which the incidence of fetal acidemia seems to be higher compared with that during labor. High-flow nasal oxygen (HFNO) can improve oxygenation better in patients with high-flow oxygen airflow. The purpose of this study is to determine whether maternal oxygen supplementation with HFNO has a positive effect on fetal acidemia during cesarean section through umbilical arterial blood gas analysis. METHOD: This prospective, single-center, randomized, double-blinded trial will enroll 120 patients undergoing cesarean section. Participants will be randomly assigned to the HFNO group or air group at a 1:1 ratio. For parturients in the HFNO group, the flow rate is 40L/min, and the oxygen is heated to 37℃ with humidity 100% oxygen concentration through the Optiflow high-flow nasal oxygen system. And for the air group, the flow rate is 2 L/min with an air pattern through the same device. The primary outcome was umbilical artery (UA) lactate. Secondary outcomes include UA pH, PO2, PCO2, BE, the incidence of pH < 7.20 and pH < 7.10, Apgar scores at 1 and 5 min, and neonatal adverse outcomes. DISCUSSION: Our study is the first trial investigating whether maternal oxygen supplementation with HFNO can reduce the umbilical artery lactate levels and the incidence of fetal acidemia in cesarean section under combined spinal-epidural anesthesia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05921955. Registered on 27 June 2023.

Comparison of reproductive toxicity between pristine and aged polylactic acid microplastics in Caenorhabditis elegans.

Caenorhabditis elegans was employed as model to compare reproductive toxicity between pristine and aged polylactic acid microplastics (PLA-MPs). Aged PLA-MPs induced by UV irradiation showed degradation reflected by decrease in size and alteration in morphological surface. Aged PLA-MPs also exhibited some certain changes of chemical properties compared to pristine PLA-MP. Compared with pristine PLA-MPs, more severe toxicity on reproductive capacity and gonad development was detected in 1-100 µg/L aged PLA-MPs. Meanwhile, aged PLA-MPs caused more severe enhancement in germline apoptosis and alterations in expressions of ced-9, ced-4, ced-3, and egl-1 governing cell apoptosis. In addition, aged PLA-MPs resulted in more severe increase in expression of DNA damage related genes (cep-1, mrt-2, hus-1, and clk-2) compared to pristine PLA-MPs, and the alterations in expression of ced-9, ced-4, ced-3, and egl-1 in pristine and aged PLA-MPs could be reversed by RNAi of cep-1, mrt-2, hus-1, and clk-2. Besides this, enhanced germline apoptosis in pristine and aged PLA-MPs exposed animals was also suppressed by RNAi of cep-1, mrt-2, hus-1, and clk-2. Therefore, our results suggested the more severe exposure risk of aged PLA-MPs than pristine PLA-MPs in causing reproductive toxicity, which was associated with the changed physicochemical properties and DNA damage induced germline apoptosis.

Level pinning of anti-PT-symmetric circuits for efficient wireless power transfer.

Wireless power transfer (WPT) technology based on magnetic resonance (a basic physical phenomenon) can directly transfer energy from the source to the load without wires and other physical contacts, and has been successfully applied to implantable medical devices, electric vehicles, robotic arms and other fields. However, due to the frequency splitting of near-field coupling, the resonant WPT system has some unique limitations, such as poor transmission stability and low efficiency. Here, we propose anti-resonance with level pinning for high-performance WPT. By introducing the anti-resonance mode into the basic WPT platform, we uncover the competition between dissipative coupling and coherent coupling to achieve novel level pinning, and construct an effective anti-parity-time (anti-PT)-symmetric non-Hermitian system that is superior to previous PT-symmetric WPT schemes. On the one hand, the eigenvalue of the anti-PT-symmetric system at resonance frequency is always pure real in both strong and weak coupling regions, and can be used to overcome the transmission efficiency decrease caused by weak coupling, as brought about by, for example, a large size ratio of the transmitter to receiver, or a long transmission distance. On the other hand, due to the level pinning effect of the two kinds of coupling mechanisms, the working frequency of the system is guaranteed to be locked, so frequency tracking is not required when the position and size of the receiver change. Even if the system deviates from the matching condition, an efficient WPT can be realized, thereby demonstrating the robustness of the level pinning. The experimental results show that when the size ratio of the transmitter coil to the receiver coil is 4.29 (which is in the weak coupling region), the transfer efficiency of the anti-PT-symmetric system is nearly 4.3 (3.2) times higher than that of the PT-symmetric system when the matching conditions are satisfied (deviated). With the miniaturization and integration of devices in mind, a synthetic anti-PT-symmetric system is used to realize a robust WPT. Anti-PT-symmetric WPT technology based on the synthetic dimension not only provides a good research platform for the study of abundant non-Hermitian physics, but also provides a means of going beyond traditional near-field applications with resonance mechanisms, such as resonance imaging, wireless sensing and photonic routing.

Self-Care Ability and Life Quality of Cured Leprosy Patients: The Mediating Effects of Social Support.

OBJECTIVES: The study explores the relationship between social support, self-care ability, and life quality of cured leprosy patients (CLPs), aiming to develop strategies to enhance their overall well-being. METHODS: From July to December 2021, we investigated the social support, self-care ability, and life quality of CLPs through three scales and analyzed the correlation between them. In addition, structural estimation modeling (SEM) was employed to analyze their correlation. RESULTS: A total of 9245 CLPs were recruited, with a male-to-female ratio of 2.19:1, and 94.04% of cured patients was 60 years or above, with predominantly home-cured patients. The scores of WHOQOL-BREF, SSRS, and ESCA were (51.39 ± 9.89), (31.87 ± 8.76), and (100.95 ± 19.75), respectively. The results indicate a poorer quality of life and social support for CLPs compared to the general population in China. Furthermore, the home group had higher scores on these scales than the leprosarium group. The correlation analysis showed significant interactions between life quality, social support, self-care ability, and various domains (p < 0.05). SEM results revealed that the direct effect of self-care ability on life quality was 0.13, and the indirect effect on quality of life through social support was 0.08. The mediating effect of social support accounted for 22.86% of the total effect in the home group. In the leprosarium group, the effect of self-care ability on quality of life was 0.14. CONCLUSIONS: Most CLPs in Jiangsu Province are concentrated in the central region, with a high disease burden. We found that CLPs have a poorer life quality than the general population, with the leprosarium group being worse than the home group. The government and society should pay more attention to and support these cured patients.

Circulating donor-derived cell-free DNA as a marker for rejection after lung transplantation.

Objective: Recently, circulating donor-derive cell free DNA (dd-cfDNA) has gained growing attention in the field of solid organ transplantation. The aim of the study was to analyze circulating dd-cfDNA levels in graft rejection, ACR and AMR separately for each rejection type compared with non-rejection, and assessed the diagnostic potential of dd-cfDNA levels in predicting graft rejection after lung transplantation. Methods: A systematic search for relevant articles was conducted on Medline, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases without restriction of languages. The search date ended on June 1, 2023. STATA software was used to analyze the difference between graft rejection, ACR, AMR and stable controls, and evaluate the diagnostic performance of circulating dd-cfDNA in detecting graft rejection. Results: The results indicated that circulating dd-cfDNA levels in graft rejection, ACR, and AMR were significantly higher than non-rejection (graft rejection: SMD=1.78, 95% CI: 1.31-2.25, I2 = 88.6%, P< 0.001; ACR: SMD=1.03, 95% CI: 0.47-1.59, I2 = 89.0%, P < 0.001; AMR: SMD= 1.78, 95% CI: 1.20-2.35, I2 = 89.8%, P < 0.001). Circulating dd-cfDNA levels distinguished graft rejection from non-rejection with a pooled sensitivity of 0.87 (95% CI: 0.80-0.92) and a pooled specificity of 0.82 (95% CI: 0.76-0.86). The corresponding SROC yield an AUROC of 0.90 (95% CI: 0.87-0.93). Conclusion: Circulating dd-cfDNA could be used as a non-invasive biomarker to distinguish the patients with graft rejection from normal stable controls. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023440467.

Seroprevalence of Chlamydia abortus and Brucella spp. and risk factors for Chlamydia abortus in pigs from China.

Chlamydiosis and brucellosis induced abortions have resulted in significant economic losses in the global livestock industry. Although there have been numerous reports on these two diseases in ruminants in China, limited information is available regarding the prevalence of Chlamydia abortus (C. abortus) and Brucella spp. infection in pigs. This study aimed to investigate the prevalence of C. abortus and Brucella spp. infections in pig serum using serology and to identify potential risk factors. In total, 2816 serum samples were collected from 12 provinces in China. The presence of C. abortus antibodies was determined using an enzyme-linked immunosorbent assay (ELISA), while the presence of Brucella spp. antibodies was examined using the Rose Bengal Plate Test (RBPT) and the Standard Agglutination Test (SAT). The seroprevalences of C. abortus and Brucella spp. were 8.38 % (236/2816) and 0.11 % (3/2816), respectively. Geographical location, season, and age were found to be risk factors associated with C. abortus infection in pig herds in China (p<0.01), and the seropositive rate for C. abortus in sow herds was strongly associated with the occurrence of abortion (p<0.01). Overall, in China, pigs exhibit a higher seroprevalence of C. abortus, whereas the prevalence of Brucella is limited. This study represents the first comprehensive survey of C. abortus and Brucella spp. in pig herds in China that established potential risk factors and provided data for the prevention and control of intraspecies and interspecies transmission of C. abortus to humans.

Gut microbiota changes in horses with Chlamydia.

BACKGROUND: Zoonotic diseases pose a significant threat to public health. Chlamydia, as an intracellular pathogen, can colonize the intestinal tract of humans and animals, changing the gut microbiota. However, only a few studies have evaluated alterations in the gut microbiota of horses infected with Chlamydia. Therefore, this study aimed to investigate gut microbiota and serum biochemical indicators in horses with Chlamydial infection (IG) and healthy horses (HG). Fecal and blood samples were collected from 16 horses (IG: 10; HG: 6) before morning feeding for the determination of gut microbiota and serum biochemical parameters. RESULTS: The results showed that total globulin (GLB), alanine aminotransferase (ALT), and creatine kinase (CK) levels were significantly increased in IG compared with HG. Notably, the gut microbial diversity increased in IG compared with HG. Furthermore, Moraxellaceae and Akkermanisa abundance decreased in IG, while Streptococcus, Treponema, Prevotella, and Paraprevotella abundances (13 genera of bacterial species) increased. Compared with HG, carbohydrate metabolism increased in IG while amino acid metabolism decreased. In addition, the abundance of 18 genera of bacteria was associated with the level of five serum biochemical indicators. CONCLUSIONS: In summary, this study elucidated the influence of Chlamydia infection in horses on the gut microbiota, unraveling consequential alterations in its composition and metabolic profile. Therefore, this study improves the understanding of Chlamydia-induced intestinal infections.

Mitochondrial IRG1 traps MCL-1 to induce hepatocyte apoptosis and promote carcinogenesis.

Hepatocarcinogenesis is initiated by repeated hepatocyte death and liver damage, and the underlying mechanisms mediating cell death and the subsequent carcinogenesis remain to be fully investigated. Immunoresponsive gene 1 (IRG1) and its enzymatic metabolite itaconate are known to suppress inflammation in myeloid cells, and its expression in liver parenchymal hepatocytes is currently determined. However, the potential roles of IRG1 in hepatocarcinogenesis are still unknown. Here, using the diethylnitrosamine (DEN)-induced hepatocarcinogenesis mouse model, we found that IRG1 expression in hepatocytes was markedly induced upon DEN administration. The DEN-induced IRG1 was then determined to promote the intrinsic mitochondrial apoptosis of hepatocytes and liver damage, thus enhancing the subsequent hepatocarcinogenesis. Mechanistically, the mitochondrial IRG1 could associate and trap anti-apoptotic MCL-1 to inhibit the interaction between MCL-1 and pro-apoptotic Bim, thus promoting Bim activation and downstream Bax mitochondrial translocation, and then releasing cytochrome c and initiating apoptosis. Thus, the inducible mitochondrial IRG1 promotes hepatocyte apoptosis and the following hepatocarcinogenesis, which provides mechanistic insight and a potential target for preventing liver injury and HCC.