Changes in epidermal thickness and their correlation with clinical characteristics in patients with vitiligo.

Vitiligo is an autoimmune disorder characterized by epidermal melanocyte damage, with the typical clinical manifestation of white patches of skin. Keratinocytes, which work in concert with melanocytes to maintain the structural and functional integrity of the skin, are implicated in the progression of vitiligo. Recent studies have reported abnormal keratinocyte proliferation and epidermal thickening in some patients with vitiligo; however, the relationship between these changes and the clinical characteristics of vitiligo remains unclear. We assessed the changes in epidermal thickness in patients with vitiligo and their correlation with clinical characteristics. Compared to the non-lesional skins, the stratum corneum, viable epidermis, and full epidermis in the lesional skins were all significantly thicker. The thickness of the stratum corneum in the head, neck, and trunk was greatly lower than that in the extremities. The thickness of the stratum corneum in the sun-exposed area was higher than that in the sun-protected area, whereas the thickness of the viable epidermis decreased. In conclusion, our study found that the epidermis in the lesional skins of patients with vitiligo was significantly thickened, especially in the sun-exposed areas and extremities.

Environmental variables improve the accuracy of remote sensing estimation of soil organic carbon content.

Accurately and quickly estimating the soil organic carbon (SOC) content is crucial in the monitoring of global carbon. Environmental variables play a significant role in improving the accuracy of the SOC content estimation model. This study focuses on modeling methodologies and environmental variables, which significantly influence the SOC content estimation model. The modeling methods used in this research comprise multiple linear regression (MLR), partial least squares regression (PLSR), random forest, and support vector machines (SVM). The analyzed environmental variables include terrain, climate, soil, and vegetation cover factors. The original spectral reflectance (OSR) of Landsat 5 TM images and the spectral reflectivity after the derivative processing were combined with the above environmental variables to estimate SOC content. The results showed that: (1) The SOC content can be efficiently estimated using the OSR of Landsat 5 TM, however, the derived processing method cannot significantly improve the estimation accuracy. (2) Environmental variables can effectively improve the accuracy of SOC content estimation, with climate and soil factors producing the most significant improvements. (3) Machine learning modeling methods provide better estimation accuracy than MLR and PLSR, especially the SVM model which has the highest accuracy. According to our observations, the best estimation model in the study area was the "OSR + SVM" model (R2 = 0.9590, RMSE = 13.9887, MAE = 10.8075), which considered four environmental factors. This study highlights the significance of environmental variables in monitoring SOC content, offering insights for more precise future SOC assessments. It also provides crucial data support for soil health monitoring and sustainable agricultural development in the study area.

Association between visceral adiposity index and incidence of diabetic kidney disease in adults with diabetes in the United States.

Visceral adiposity index (VAI) is a reliable indicator of visceral adiposity. However, no stu-dies have evaluated the association between VAI and DKD in US adults with diabetes. Theref-ore, this study aimed to explore the relationship between them and whether VAI is a good pr-edictor of DKD in US adults with diabetes. Our cross-sectional study included 2508 participan-ts with diabetes who were eligible for the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Univariate and multivariate logistic regression were used to an-alyze the association between VAI level and DKD. Three models were used to control for pot-ential confounding factors, and subgroup analysis was performed for further verification. A tot-al of 2508 diabetic patients were enrolled, of whom 945 (37.68%) were diagnosed with DKD. Overall, the VAI was 3.36 ± 0.18 in the DKD group and 2.76 ± 0.11 in the control group. VAI was positively correlated with DKD (OR = 1.050, 95% CI 1.049, 1.050) after fully adjusting for co-nfounding factors. Compared with participants in the lowest tertile of VAI, participants in the highest tertile of VAI had a significantly increased risk of DKD by 35.9% (OR = 1.359, 95% CI 1.355, 1.362). Through subgroup analysis, we found that VAI was positively correlated with the occurrence of DKD in all age subgroups, male(OR = 1.043, 95% CI 1.010, 1.080), participants wit-hout cardiovascular disease(OR = 1.038, 95% CI 1.011, 1.069), hypertension (OR = 1.054, 95% CI 1.021, 1.090), unmarried participants (OR = 1.153, 95% CI 1.036, 1.294), PIR < 1.30(OR = 1.049, 95% CI 1.010, 1.094), PIR ≧ 3 (OR = 1.085, 95% CI 1.021, 1.160), BMI ≧ 30 kg/m2 (OR = 1.050, 95% CI 1.016, 1.091), former smokers (OR = 1.060, 95% CI 1.011, 1.117), never exercised (OR = 1.033, 95% CI 1.004, 1.067), non-Hispanic white population (OR = 1.055, 95% CI 1.010, 1.106) and non-Hipanic black population (OR = 1.129, 95% CI 1.033, 1.258). Our results suggest that elevated VAI levels are closely associated with the development of DKD in diabetic patients. VAI may be a simpl-e and cost-effective index to predict the occurrence of DKD. This needs to be verified in furt-her prospective investigations.

Lattice Strain Regulation and Halogen Vacancies Passivation Enable High-Performance Formamidine-Based Perovskite Solar Cells.

Formamidinium lead iodide (FAPbI3) perovskite has lately surfaced as the preferred contender for highly proficient and robust perovskite solar cells (PSCs), owing to its favorable bandgap and superior thermal stability. Nevertheless, volatilization and migration of iodide ions (I-) result in non-radiating recombination centers, and the presence of large formamidine (FA) cations tends to cause lattice strain, thereby reducing the power conversion efficiency (PCE) and stability of PSCs. To solve these problems, the lead formate (PbFa) is added into the perovskite solution, which effectively mitigates the halogen vacancy and provides tensile strain outside the perovskite lattice, thereby enhancing its properties. The strong coordination between the C═O of HCOO- and Pb-I backbones effectively immobilizes anions, significantly increases the energy barrier for anion vacancy formation and migration, and reduces the risk of lead ion (Pb2+) leakage, thereby improving the operation and environmental safety of the device. Consequently, the champion PCE of devices with Ag electrodes can be increased from 22.15% to 24.32%. The unencapsulated PSCs can still maintain 90% of the original PCE even be stored in an N2 atmosphere for 1440 h. Moreover, the target devices have significantly improved performance in terms of light exposure, heat, or humidity.

[Retracted] Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the immunofluorescence data featured in Fig. 1H, TUNEL assay data in Fig. 2A, cytochome c leakage assay data in Fig. 2H, staining of cardiolipin images in Fig. 2H, lamellipodia­stained data in Fig. 3A, and immunofluorescence assay data in Figs. 3F and 5D were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Oncology Reports, or were under consideration for publication at around the same time (several of which have now been retracted). In addition, overlapping sections of data were noted within the data panels in Fig. 3D and F, such that data which were intended to represent the results from differently performed experiments had apparently been derived from the same original source(s). In view of the fact that certain of these data had already apparently been published prior to the submission of this article for publication, and in view of an overall lack of confidence in the presented data, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 1671­1681, 2018; DOI: 10.3892/or.2018.6252].

Covalent Triazine Based Frameworks with Donor-Donor-π-Acceptor Structures for Dendrite-Free Lithium Metal Batteries.

The appearance of disordered lithium dendrites and fragile solid electrolyte interfaces (SEI) significantly hinder the serviceability of lithium metal batteries. Herein, guided by theoretical predictions, a multi-component covalent triazine framework with partially electronegative channels (4C-TA0.5TF0.5-CTF) is incorporated as a protective layer to modulate the interface stability of the lithium metal batteries. Notably, the 4C-TA0.5TF0.5-CTF with optimized electronic structure at the molecular level by fine-tuning the local acceptor-donor functionalities not only enhances the intermolecular interaction thereby providing larger dipole moment and improved crystallinity and mechanical stress, but also facilitates the beneficial effect of lithiophilic sites (C-F bonds, triazine cores, C=N linkages and aromatic rings) to further regulate the migration of Li+ and achieve a uniform lithium deposition behavior as determined by various in-depth in/ex situ characterizations. Due to the synergistic effect of multi-component organic functionalities, the 4C-TA0.5TF0.5-CTF modified full cells perform significantly better than the common two/three-component 2C-TA-CTF and 3C-TF-CTF electrodes, delivering an excellent capacity of 116.3 mAh g-1 (capacity retention ratio: 86.8%) after 1000 cycles at 5 C and improved rate capability. This work lays a platform for the prospective molecular design of improved organic framework relative artificial SEI for highly stable lithium metal batteries.

Multifunctional SnO2 QDs/MXene Heterostructures as Laminar Interlayers for Improved Polysulfide Conversion and Lithium Plating Behavior.

Poor cycling stability in lithium-sulfur (Li-S) batteries necessitates advanced electrode/electrolyte design and innovative interlayer architectures. Heterogeneous catalysis has emerged as a promising approach, leveraging the adsorption and catalytic performance on lithium polysulfides (LiPSs) to inhibit LiPSs shuttling and improve redox kinetics. In this study, we report an ultrathin and laminar SnO2@MXene heterostructure interlayer (SnO2@MX), where SnO2 quantum dots (QDs) are uniformly distributed across the MXene layer. The combined structure of SnO2 QDs and MXene, along with the creation of numerous active boundary sites with coordination electron environments, plays a critical role in manipulating the catalytic kinetics of sulfur species. The Li-S cell with the SnO2@MX-modified separator not only demonstrates superior electrochemical performance compared to cells with a bare separator but also induces homogeneous Li deposition during cycling. As a result, an areal capacity of 7.6 mAh cm-2 under a sulfur loading of 7.5 mg cm-2 and a high stability over 500 cycles are achieved. Our work demonstrates a feasible strategy of utilizing a laminar separator interlayer for advanced Li-S batteries awaiting commercialization and may shed light on the understanding of heterostructure catalysis with enhanced reaction kinetics.

Human impacts overwhelmed climate as the dominant factor controlling lacustrine organic matter accumulation in Erhai Lake 2000 years ago, Southwest China.

Climate and human activity are two important factors in regulating organic matter (OM) accumulation in the lake environment. However, when and how anthropogenic impacts have affected lacustrine OM accumulation in southwest China during the late Holocene have not yet been well defined. Here, a 16.3-kyr n-alkane record derived from Erhai Lake was used to trace OM sources and explore their connections to climate and human activity. The n-alkane distributions indicated that the dominant sediment sources shifted from terrestrial and aquatic plants to algae in the late Holocene. OM accumulation was closely related to catchment soil erosion, sediment transport, and deposition processes regulated by climate conditions before 5.0 cal. kyr B.P., following the patterns that stronger monsoon precipitation favoured more terrestrial and less aquatic OM input, and vice versa. From 5.0 to 2.0 cal. kyr B.P., the synchronous downwards trends in terrestrial OM input and precipitation intensity indicated that climate remained a major driving force for OM accumulation. However, sediment sources experienced large-magnitude and centennial-scale oscillations between allochthonous and autochthonous inputs, reflecting early human impacts appeared and lake ecosystems retained the self-regulated ability to recover from the basin-wide early moderate human disturbances. Afterwards, the increased (decreased) OM contributions from terrestrial (aquatic) plants contradicted the weakening monsoon precipitation since 2.0 cal. kyr B.P., indicating a dominant effect of human activities on OM accumulation. This change was accompanied by highly improved algae productivity and gradually elevated lacustrine trophic status, and the lake ecosystem eventually shifted into another state largely deviating from its climate-driven background due to intensified deforestation and agricultural cultivation. Regional comparison indicated that anthropogenic disturbances have temporal differences in southwest China. This study will further improve our understanding of past climate-human-environment interactions in southwest China.

Recognition of small water bodies under complex terrain based on SAR and optical image fusion algorithm.

Understanding the spatial and temporal distribution of small water bodies is essential for managing water resources, crafting conservation policies, and preserving watershed ecosystems and biodiversity. However, existing studies often rely on a single remote sensing data source (optical or microwave), focusing on large-scale, flat areas and lacking comprehensive monitoring of small water bodies in complex terrain. Therefore, considering the complementary advantages of multisource remote sensing (multispectral and SAR), this paper proposes a multispectral and SAR fusion algorithm, named Multispectral and SAR Fusion algorithm (MASF), to better capture the remote sensing characteristics of small water bodies in complex areas. Based on this, a dataset containing spectral, texture, and geometric features is constructed, and multi-scale segmentation and random forest algorithms are applied for identification of small water bodies in complex terrain. The results demonstrate that the proposed fusion algorithm MASF exhibits minimal spectral distortion (SAM < 3.5, ERGAS <21, RMSE <0.01) and robust spatial feature enhancement (PSNR >40, SSIM >0.999, CC > 0.99). The Overall Accuracy (OA) and Kappa coefficients for both experimental areas surpassed 0.9. For rivers and reservoirs, both Producer's Accuracy (PA) and User's Accuracy (UA) exceeded 0.9. The UA for agricultural ponds exceeded 0.8. Comparative analysis with three other types of water-related data products shows that the freshwater identification results in this study have certain advantages in local small water bodies. Our research holds significant implications for the utilization of water resources in mountainous areas, prevention and control of floods and floods, as well as the development of aquaculture industry.

[Retracted] NR4A1­induced increase in the sensitivity of a human gastric cancer line to TNFα­mediated apoptosis is associated with the inhibition of JNK/Parkin­dependent mitophagy.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the data shown in Figs. 2A and 4F were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that were submitted to their respective journals at around the same time; moreover, the same data had apparently been included in the western blots featured in Fig. 5A to show the Parkin and mito­LCIII protein bands. As it was not clear what had been the original venue for the submission of the strikingly similar data here, the Editor requested that the authors send to us all the raw data underlying the affected figures; however, the authors were not able to comply with this request at the time of asking. Given that the authors were unable to provide the supporting data as requested, the Editor of International Journal of Oncology has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 52: 367­378, 2018; DOI: 10.3892/ijo.2017.4216].

Identification and transcriptional response of ATP-binding cassette transporters to beta-cypermethrin in the poultry red mite, Dermanyssus gallinae.

Dermanyssus gallinae, a worldwide pest in birds, has developed varying degrees of resistance to insecticides. The ATP-binding cassette (ABC) transporters are essential for the removal of xenobiotics from arthropods. However, our knowledge about ABC transporter proteins in D. gallinae is limited. Forty ABC transporters were identified in the transcriptome and genome of D. gallinae. The resistant population displayed an augmented metabolic rate for beta-cypermethrin compared to the susceptible group, with a remarkable increase in the content of ABC transporters. Verapamil was found able to increase the toxicity of beta-cypermethrin in the resistant population. Results from qRT-PCR analysis showed that eleven ABC transcripts were more highly expressed in the resistant population than the susceptible group at all stages of development, and beta-cypermethrin was observed to be able to induce the expression of DgABCA5, DgABCB4, DgABCD3, DgABCE1 and DgABCG5 in D. gallinae. RNAi-mediated knockdown of the five genes was observed to increase the susceptibility of resistant mites to beta-cypermethrin. These results suggest that ABC transporters, DgABCA5, DgABCB4, DgABCD3, DgABCE1 and DgABCG5 genes, may be related to beta-cypermethrin resistance in D. gallinae. This research will serve as a foundation for further studies on mechanism of insecticide resistance, which could be beneficial for controlling D. gallinae.

Point mutations in the voltage-gated sodium channel gene conferring pyrethroid resistance in China populations of the Dermanyssus gallinae.

BACKGROUND: Dermanyssus gallinae, the poultry red mite (PRM), is a worldwide ectoparasite posing significant economic challenges in poultry farming. The extensive use of pyrethroids for PRM control has led to the emergence of pyrethroid resistance. The objective of this study is to detect the pyrethroid resistance and explore its associated point mutations in the voltage-gated sodium channel (VGSC) gene among PRM populations in China. RESULTS: Several populations of D. gallinae, namely CJF-1, CJP-2, CJP-3, CSD-4 and CLD-5, displayed varying degrees of resistance to beta-cypermethrin compared to a susceptible field population (CBP-5). Mutations of VGSC gene in populations of PRMs associated with pyrethroid resistance were identified through sequencing its fragments IIS4-IIS5 and IIIS6. The mutations I917V, M918T/L, A924G and L925V were present in multiple populations, while no mutations were found at positions T929, I936, F1534 and F1538. CONCLUSION: The present study confirmed the presence of extremely high levels of pyrethroid resistance in PRM populations in China, and for the first time detected four pyrethroid resistance mutations in the VGSC gene. Identifying pyrethroid resistance in the field population of PRM in China can be achieved through screening for VGSC gene mutations as an early detection method. Our findings underscore the importance of implementing chemical PRM control strategies based on resistance evidence, while also considering the management of acaricide resistance in the control of PRMs. © 2024 Society of Chemical Industry.

Self-nanomicellizing solid dispersion: A promising platform for oral drug delivery.

Amorphous solid dispersion (ASD) has been widely used to enhance the oral bioavailability of water-insoluble drugs for oral delivery because of its advantages of enhancing solubility and dissolution rate. However, the problems related to drug recrystallization after drug dissolution in media or body fluid have constrained its application. Recently, a self-nanomicellizing solid dispersion (SNMSD) has been developed by incorporating self-micellizing polymers as carriers to settle the problems, markedly improving the ability of supersaturation maintenance and enhancing the oral bioavailability of drug. Spontaneous formation and stability of the self-nanomicelle (SNM) have been proved to be the key to supersaturation maintenance of SNMSD system. This offers a novel research direction for maintaining supersaturation and enhancing the bioavailability of ASDs. To delve into the advantages of SNMSDs, we provide a concise review introducing the formation mechanism, characterization methods and stability of SNMs, emphasizing the advantages of SNMSDs for oral drug delivery facilitated by SNM formation, and discussing relevant research prospects.

Exploration of poly (ADP-ribose) polymerase inhibitor resistance in the treatment of BRCA1/2-mutated cancer.

Breast cancer susceptibility 1/2 (BRCA1/2) genes play a crucial role in DNA damage repair, yet mutations in these genes increase the susceptibility to tumorigenesis. Exploiting the synthetic lethality mechanism between BRCA1/2 mutations and poly(ADP-ribose) polymerase (PARP) inhibition has led to the development and clinical approval of PARP inhibitor (PARPi), representing a milestone in targeted therapy for BRCA1/2 mutant tumors. This approach has paved the way for leveraging synthetic lethality in tumor treatment strategies. Despite the initial success of PARPis, resistance to these agents diminishes their efficacy in BRCA1/2-mutant tumors. Investigations into PARPi resistance have identified replication fork stability and homologous recombination repair as key factors sensitive to PARPis. Additionally, studies suggest that replication gaps may also confer sensitivity to PARPis. Moreover, emerging evidence indicates a correlation between PARPi resistance and cisplatin resistance, suggesting a potential overlap in the mechanisms underlying resistance to both agents. Given these findings, it is imperative to explore the interplay between replication gaps and PARPi resistance, particularly in the context of platinum resistance. Understanding the impact of replication gaps on PARPi resistance may offer insights into novel therapeutic strategies to overcome resistance mechanisms and enhance the efficacy of targeted therapies in BRCA1/2-mutant tumors.

Temporal alteration of serum bilirubin levels and its renoprotective effects in diabetic kidney disease: exploring the hormonal mechanisms.

Objective: This current study represents a novel endeavor to scrutinize the correlation between the temporal alteration in serum total bilirubin (TBIL) concentrations and the rate of estimated glomerular filtration rate (eGFR). Additionally, this study aims to probe the plausible molecular mechanism underpinning the renoprotective effects of bilirubin concerning its hormonal characteristics. Materials and methods: In this study, a cohort of 103 patients diagnosed with DKD and receiving medical care at Dongzhimen Hospital were recruited and monitored over a period of 2-7 years. The progression of DKD was ascertained using a threshold of eGFR decline > -5.48%/year. To assess the relationship between the annual change in serum TBIL levels (%/year) and the slope of eGFR, multivariate binary logistic regression analysis was employed. Furthermore, the ROC curve analysis was employed to determine the cut-off value for TBIL levels (%/year). Results: The use of multivariate binary logistic regression models revealed that serum TBIL levels (%/year) exhibited a significant correlation with the slope of eGFR. Moreover, the ROC curve analysis indicated a cut-off value of -6.729%/year for TBIL levels (%/year) with a sensitivity of 0.75 and specificity of 0.603, in diagnosing eGFR decline >-5.48%/year. Conclusions: The findings of this study suggest that the sustained elevation of serum bilirubin concentration within the physiological range can effectively retard the progression of Diabetic Kidney Disease (DKD). Furthermore, the hormonal attributes of bilirubin may underlie its renoprotective effects.

IGF2BP2 regulates the inflammation of fibroblast-like synoviocytes via GSTM5 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with an unknown etiology. RA cannot be fully cured and requires lengthy treatment, imposing a significant burden on both individuals and society. Due to the lack of specific drugs available for treating RA, exploring a key new therapeutic target for RA is currently an important task. Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the progression of RA, which release interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α resulting in abnormal inflammatory reaction in the synovium. A previous study has highlighted the correlation of m6A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) with inflammation-related diseases in human. However, the role of IGF2BP2 in the inflammatory reaction of FLSs during RA progression has not been assessed. In this study, IGF2BP2 expression was decreased in the synovial tissues of RA patients and collagen-induced arthritis (CIA) rats. Intra-articular injection of an adeno-associated virus (AAV) vector overexpressing IGF2BP2 relieved paw swelling, synovial hyperplasia and cartilage destruction in CIA rats. IGF2BP2 overexpression also inhibited lipopolysaccharide (LPS)-mediated RA fibroblast-like synoviocytes (RA-FLSs) migration and invasion accompanied by a decreased level of inflammatory factors in vitro. Conversely, IGF2BP2 suppression promoted RA-FLSs migration and invasion with an elevated level of inflammatory factors in vitro. The sequencing result showed that glutathione S-transferase Mu 5 (GSTM5), a key antioxidant gene, was the target mRNA of IGF2BP2. Further experiments demonstrated that IGF2BP2 strengthened the stability of GSTM5 mRNA, leading to weakened inflammatory reaction and reduced expression of matrix metalloproteinase 9 and 13 (MMP9, MMP13). Therefore, IGF2BP2-GSTM5 axis may represent a potential therapeutic target for RA treatment.

Enhancing Orbital Interaction in Spinel LiNi0.5Mn1.5O4 Cathode for High-Voltage and High-Rate Li-Ion Batteries.

High voltage cobalt-free spinel LiNi0.5Mn1.5O4 (LNMO) is well organized as a high-power cathode material for lithium (Li)-ion batteries, however, the weak interaction between the 3d orbital of the transition metal (TM) ions and the 2p orbital of oxygen (O) leads to the instability of crystal structural, hindering the long-term stable cycling of LNMO cathode especially at high temperatures. Here, a design strategy of orbital interaction is initiated to strengthen TM 3d-O 2p framework in P-doped LNMO (P-LNMO) by choosing phytic acid as P dopant, which can realize more uniform doping compared to regular phosphate. The results show that the enhancement of TM 3d-O 2p orbital interaction in P-LNMO can suppress the Jahn-Teller effect and subsequent dissolution of Mn, as well as lowers the energy barrier for Li ion insertion/extraction kinetics. As a result, superior electrochemical performances including high discharge capacity, stable cycling behavior and enhanced rate capability of P-LNMO are obtained. Significantly, the P-LNMO pouch cell shows great cycling stability with 97.4% capacity retention after 100 cycles.

CRF08_BC subtype is more prone to ART failure and new-generation NNRTI-resistance under long-term first-line ART.

OBJECTIVE: To investigate the characteristics of drug resistance mutations (DRMs) and their contextual influence on drug susceptibility in CRF07_BC and CRF_08BC subtypes. METHODS: Patients with virological failure were genotyped using phylogenetic analysis. DRMs and susceptibility to antiretroviral drugs were analysed using the Stanford University HIV Drug Resistance Database. RESULTS: Six HIV subtypes were identified among 1296 successfully amplified sequences, with the CRF07_BC subtype prevailing at a rate of 91.7%, followed by CRF08_BC. Overall, the CRF07_BC and CRF08_BC subtypes were similar in the distribution and frequency of DRMs, the most common DRMs were K103N and M184V. However, among patients with antiretroviral therapy duration of ≥3 y who developed resistance, CRF08_BC exhibited a higher mutation frequency at sites 184, 138, 221, and 188 (Chi-square test, P < 0.05), and compared with CRF07_BC, patients with CRF08_BC had higher prevalence of abacavir, emtricitabine, lamivudine, doravirine, etravirine, and rilpivirine resistance. Moreover, there was an increased prevalence of cross-resistance between efavirenz/nevirapine and new-generation NNRTIs in patients with CRF08_BC; doravirine (r = 1.0), rilpivirine (r = 0.93), and etravirine (r = 0.86) resistance highly correlated with efavirenz/nevirapine. CONCLUSIONS: The present study provides valuable insights into the profile of DRMs and resistance patterns in patients with CRF07_BC and CRF08_BC experiencing treatment failure in Butuo. These findings have the potential to contribute to future strategies for HIV control and treatment.

Chk2 Modulates Bmi1-Deficiency-Induced Renal Aging and Fibrosis via Oxidative Stress, DNA Damage, and p53/TGFß1-Induced Epithelial-Mesenchymal Transition.

Renal aging may lead to fibrosis and dysfunction, yet underlying mechanisms remain unclear. We explored whether deficiency of the Polycomb protein Bmi1 causes renal aging via DNA damage response (DDR) activation, inducing renal tubular epithelial cell (RTEC) senescence and epithelial-mesenchymal transition (EMT). Bmi1 knockout mice exhibited oxidative stress, DDR activation, RTEC senescence, senescence-associated secretory phenotype (SASP), and age-related fibrosis in kidneys. Bmi1 deficiency impaired renal structure and function, increasing serum creatinine/urea, reducing creatinine clearance, and decreasing cortical thickness and glomerular number. However, knockout of the serine-threonine kinase Chk2 alleviated these aging phenotypes. Transcriptomics identified transforming growth factor beta 1 (TGFß1) upregulation in Bmi1-deficient RTECs, but TGFß1 was downregulated upon Chk2 knockout. The tumor suppressor protein p53 transcriptionally activated TGFß1, promoting EMT in RTECs. Bmi1 knockout or oxidative stress (induced with H2O2) increased TGFß1 expression, and EMT in RTECs and was partly reversed by p53 inhibition. Together, Bmi1 deficiency causes oxidative stress and DDR-mediated RTEC senescence/SASP, thus activating p53 and TGFß1 to induce EMT and age-related fibrosis. However, blocking DDR (via Chk2 knockout) or p53 ameliorates these changes. Our study reveals mechanisms whereby Bmi1 preserves renal structure and function during aging by suppressing DDR and p53/TGFß1-mediated EMT. These pathways represent potential targets for detecting and attenuating age-related renal decline.

From genomic insights to clinical hope: Targeting NEU1 in IgA nephropathy.

BACKGROUND: IgA Nephropathy (IgAN), the primary form of glomerulonephritis, presents significant clinical challenges due to its obscure pathogenesis and lack of targeted treatments. We conducted a proteome-wide Mendelian randomization (MR) study to identify therapeutic targets for IgAN. METHODS: Utilizing a plasma proteome dataset comprising 4907 blood plasma proteins as the exposure variable, and renal biopsy-confirmed IgAN cases as the outcome, this study employed MR to pinpoint proteins potentially pathogenic to IgAN. The robustness of our findings was affirmed through external dataset validation, reverse causation testing, and Bayesian colocalization analysis. Additionally, we conducted phenotypic scanning and analyzed downstream metabolites to investigate candidate proteins's biological function. RESULTS: In our study, a significant association was identified between an increase in neuraminidase 1 (NEU1) expression and the risk of IgAN. Specifically, a one standard deviation increase in NEU1 expression was associated with an odds ratio of 11.80 for the development of IgAN (95% confidence interval: 4.03-34.54). This association was substantiated across various statistical models and external validations. Colocalization analysis indicated a shared causal variant between NEU1 expression and IgAN. Furthermore, an increased influenza risk associated with NEU1 was observed, supporting the therapeutic potential of NEU1 inhibitors for IgAN. However, our study found no significant role for neuraminic acid-related metabolites in IgAN's development, suggesting an independent pathway for NEU1's influence. CONCLUSION: This study identifies NEU1 as a promising therapeutic target for IgAN, backed by robust genetic evidence. Future research should explore NEU1's therapeutic potential in diverse populations and clinical scenarios, further establishing its role in IgAN.