High molecular weight hyaluronic acid-liposome delivery system for efficient transdermal treatment of acute and chronic skin photodamage.

Photodamage is one of the most common causes of skin injury. High molecular weight hyaluronic acid (HHA) has shown immense potential in the treatment of skin photodamage by virtue of its anti-inflammatory, reparative, and antioxidative properties. However, due to its large molecular structure of HHA, HHA solution could only form a protective film on the skin surface in conventional application, failing to effectively penetrate the skin, which necessitates the development of new delivery strategies. Liposomes, with a structure similar to biological membranes, have garnered extensive attention as transdermal drug delivery carriers because of their advantages in permeability, dermal compatibility, and biosafety. Herein, we have developed a HHA-liposome transdermal system (HHL) by embedding HHA into the liposome structure using reverse evaporation, high-speed homogenization, and micro-jet techniques. The effective penetration and long-term residence of HHA in skin tissue were multidimensionally verified, and the kinetics of HHA in the skin were extensively studied. Moreover, it was demonstrated that HHL significantly strengthened the activity of human keratinocytes and effectively inhibits photo-induced cellular aging in vitro. Furthermore, a murine model of acute skin injury induced by laser ablation was established, where the transdermal system showed significant anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair, thereby demonstrating immense potential in accelerating skin wound healing. Meanwhile, HHL significantly ameliorated skin barrier dysfunction caused by simulated sunlight exposure, inhibited skin erythema, inflammatory responses, and oxidative stress, and promoted collagen expression in a chronic photodamage skin model. Therefore, this transdermal delivery system with biocompatibility represents a promising new strategy for the non-invasive application of HHA in skin photodamage, revealing the significant potential for clinical translation and broad application prospects. STATEMENT OF SIGNIFICANCE: The transdermal system utilizing hyaluronic acid-based liposomes enhances skin permeability and retains high molecular weight hyaluronic acid (HHL). In vitro experiments with human keratinocytes demonstrate significant skin repair effects of HHL and its effective inhibition of cellular aging. In an acute photodamage model, HHL exhibits stronger anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair. In a chronic photodamage model, HHL significantly improves skin barrier dysfunction, reduces oxidative stress induced by simulated sunlight, and enhances collagen expression.

Ultrasound and computed tomography angiography diagnosis of fetal right atrial isomerism with cardiac total anomalous pulmonary venous connection and intestinal malrotation: a case report and literature review.

Right atrial isomerism is a rare and severe isomerism. It is frequently associated with complex congenital heart disease and various extracardiac anomalies. Imaging diagnosis of right atrial isomerism is a challenge. Multisystem and complex anomalies in a 24-week-old fetus were diagnosed with prenatal ultrasound, postnatal computed tomography angiography (CTA), and autopsy. The ultrasound detected most major cardiovascular anomalies including right atrial isomerism and total anomalous pulmonary venous connection. The CTA further detected thoracic and abdominal malformations such as bilateral morphologically right bronchus, diaphragmatic hernia, asplenia, midline liver, and intestinal malrotation. The autopsy confirmed both ultrasound and CTA findings with additional findings, namely, bilateral trilobed lungs and bilateral morphological right auricles. Prenatal ultrasound and postnatal CTA can be complementary to each other in detecting multi-system complex anomalies. Their combined use can be useful for prenatal counseling and postpartum management.

TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin.

Hepatitis B virus (HBV) infection poses a significant burden on global public health. Unfortunately, current treatments cannot fully alleviate this burden as they have limited effect on the transcriptional activity of the tenacious covalently closed circular DNA (cccDNA) responsible for viral persistence. Consequently, the HBV life cycle should be further investigated to develop new anti-HBV pharmaceutical targets. Our previous study discovered that the host gene TMEM203 hinders HBV replication by participating in calcium ion regulation. The involvement of intracellular calcium in HBV replication has also been confirmed. In this study, we found that transient receptor potential vanilloid 4 (TRPV4) notably enhances HBV reproduction by investigating the effects of several calcium ion-related molecules on HBV replication. The in-depth study showed that TRPV4 promotes hepatitis B core/capsid protein (HBc) protein stability through the ubiquitination pathway and then promotes the nucleocapsid assembly. HBc binds to cccDNA and reduces the nucleosome spacing of the cccDNA-histones complex, which may regulate HBV transcription by altering the nucleosome arrangement of the HBV genome. Moreover, our results showed that TRPV4 promotes cccDNA-dependent transcription by accelerating the methylation modification of H3K4. In conclusion, TRPV4 could interact with HBV core protein and regulate HBV during transcription and replication. These data suggest that TRPV4 exerts multifaceted HBV-related synergistic factors and may serve as a therapeutic target for CHB.

Circadian rhythm response and its effect on photosynthetic characteristics of the Lhcb family genes in tea plant.

BACKGROUND: The circadian clock, also known as the circadian rhythm, is responsible for predicting daily and seasonal changes in the environment, and adjusting various physiological and developmental processes to the appropriate times during plant growth and development. The circadian clock controls the expression of the Lhcb gene, which encodes the chlorophyll a/b binding protein. However, the roles of the Lhcb gene in tea plant remain unclear. RESULTS: In this study, a total of 16 CsLhcb genes were identified based on the tea plant genome, which were distributed on 8 chromosomes of the tea plant. The promoter regions of CsLhcb genes have a variety of cis-acting elements including hormonal, abiotic stress responses and light response elements. The CsLhcb family genes are involved in the light response process in tea plant. The photosynthetic parameter of tea leaves showed rhythmic changes during the two photoperiod periods (48 h). Stomata are basically open during the day and closed at night. Real-time quantitative PCR results showed that most of the CsLhcb family genes were highly expressed during the day, but were less expressed at night. CONCLUSIONS: Results indicated that CsLhcb genes were involved in the circadian clock process of tea plant, it also provided potential references for further understanding of the function of CsLhcb gene family in tea plant.

High TPX2 expression results in poor prognosis, and Sp1 mediates the coupling of the CX3CR1/CXCL10 chemokine pathway to the PI3K/Akt pathway through targeted inhibition of TPX2 in endometrial cancer.

INTRODUCTION: Approximately 30% of individuals with advanced EC have unsatisfactory prognosis. Evidence suggests that TPX2 is frequently upregulated in malignancies and related to cancer progression. Its role and pathological mechanism in EC need further research. METHODS: GSEA and TPX2 expression, GO, KEGG, and prognostic analyses were performed with TCGA data by bioinformatic approaches. Relationships between TPX2 expression and clinicopathological parameters were investigated immunohistochemically and statistically. shRNA and overexpression plasmids were constructed and transfected into AN3CA and Ishikawa cells to evaluate phenotypic changes and injected into nude mouse axillae. Coimmunoprecipitation and chromatin immunoprecipitation were used to identify interacting proteins and promoter-binding sequences. Changes in TPX2 expression were identified by Western blotting and RT-qPCR. RESULTS: TPX2 expression was significantly higher in EC tissues than in normal tissues in TCGA and in-house specimens (all p < 0.001). In survival analysis, high TPX2 expression was associated with poor prognosis (p = 0.003). TPX2 overexpression stimulated cancer cell proliferation, promoted the G0-G1-to-G2/M transition, enhanced invasion and migration, and accelerated tumor growth in nude mice. TPX2 regulated the CX3CR1/CXCL10 chemokine pathway and activated the PI3K/Akt signaling pathway. Sp1 negatively regulated TPX2 expression, affecting the malignant progression of endometrial cancer cells by coupling the CX3CR1/CXCL10 chemokine pathway to the PI3K/Akt signaling pathway. CONCLUSION: TPX2 could be a prognostic biomarker for EC and play an important role in the CX3CR1/CXCL10 chemokine pathway and PI3K/Akt pathway via Sp1.

CsPAT1, a GRAS transcription factor, promotes lignin accumulation by antagonistic interacting with CsWRKY13 in tea plants.

Lignin is an important component of plant cell walls and plays crucial roles in the essential agronomic traits of tea quality and tenderness. However, the molecular mechanisms underlying the regulation of lignin biosynthesis in tea plants remain unclear. CsWRKY13 acts as a negative regulator of lignin biosynthesis in tea plants. In this study, we identified a GRAS transcription factor, phytochrome A signal transduction 1 (CsPAT1), that interacts with CsWRKY13. Silencing CsPAT1 expression in tea plants and heterologous overexpression in Arabidopsis demonstrated that CsPAT1 positively regulates lignin accumulation. Further investigation revealed that CsWRKY13 directly binds to the promoters of CsPAL and CsC4H and suppresses transcription of CsPAL and CsC4H. CsPAT1 indirectly affects the promoter activities of CsPAL and CsC4H by interacting with CsWRKY13, thereby facilitating lignin biosynthesis in tea plants. Compared with the expression of CsWRKY13 alone, the co-expression of CsPAT1 and CsWRKY13 in Oryza sativa significantly increased lignin biosynthesis. Conversely, compared with the expression of CsPAT1 alone, the co-expression of CsPAT1 and CsWRKY13 in O. sativa significantly reduced lignin accumulation. These results demonstrated the antagonistic regulation of the lignin biosynthesis pathway by CsPAT1 and CsWRKY13. These findings improve our understanding of lignin biosynthesis mechanisms in tea plants and provide insights into the role of the GRAS transcription factor family in lignin accumulation.

Radiomics analysis based on multiparametric magnetic resonance imaging for differentiating early stage of cervical cancer.

Objective: To investigate the performance of multiparametric magnetic resonance imaging (MRI)-based radiomics models in differentiating early stage of cervical cancer (Stage I-IIa vs. IIb-IV). Methods: One hundred patients with cervical cancer who underwent preoperative MRI between June 2020 and March 2022 were retrospectively enrolled. Training (n = 70) and testing cohorts (n = 30) were assigned by stratified random sampling. The clinical and pathological features, including age, histological subtypes, tumor grades, and node status, were compared between the two cohorts by t-test or chi-square test. Radiomics features were extracted from each volume of interest (VOI) on T2-weighted images (T2WI) and apparent diffusion coefficient (ADC) maps. The data balance of the training cohort was resampled by synthesizing minority oversampling techniques. Subsequently, the adiomics signatures were constructed by the least absolute shrinkage and selection operator algorithm and minimum-redundancy maximum-relevance with 10-fold cross-validation. Logistic regression was applied to predict the cervical cancer stages (low [I-IIa]) and (high [IIb-IV] FIGO stages). The receiver operating characteristic curve (area under the curve [AUC]) and decision curve analysis were used to assess the performance of the radiomics model. Results: The characteristics of age, histological subtypes, tumor grades, and node status were not significantly different between the low [I-IIa] and high [IIb-IV] FIGO stages (p > 0.05 for both the training and test cohorts). Three models based on T2WI, ADC maps, and the combined were developed based on six radiomics features from T2WI and three radiomics features from ADC maps, with AUCs of 0.855 (95% confidence interval [CI], 0.777-0.934) and 0.823 (95% CI, 0.727-0.919), 0.861 (95% CI, 0.785-0.936) and 0.81 (95% CI, 0.701-0.918), 0.934 (95% CI, 0.884-0.984) and 0.902 (95% CI, 0.832-0.972) in the training and test cohorts. Conclusion: The radiomics models combined T2W and ADC maps had good predictive performance in differentiating the early stage from locally advanced cervical cancer.

Effect of suspended particulate matter on physiological, biochemical and photosynthetic characteristics of Chlorella pyrenoidosa in the Jinjiang Estuary (Fujian, China).

Suspended particulate matter (SPM), an important component of the natural water environment, can act as a carrier of many pollutants that affect aquatic organisms. In the present study, the effect of SPM obtained from Jinjiang Estuary on the physiological, biochemical, and photosynthetic properties of typical freshwater algae (Chlorella pyrenoidosa) was investigated. The results showed that under different concentrations of SPM treatment, the superoxide dismutase (SOD), catalase (CAT) activities, and malondialdehyde (MDA) content of C. pyrenoidosa increased, but the soluble protein content decreased. SPM with different particle sizes had less effect on SOD of C. pyrenoidosa, but showed a promoting effect on CAT and MDA as well as soluble protein content. In terms of photosynthetic activity, high concentrations (70, 90 mg/L) and small particle sizes (0-75, 75-120 µm) of SPM had a greater effect on the chlorophyll a content of C. pyrenoidosa. In addition, different concentrations of SPM had no significant effect on the potential photosynthetic activity of PS II (Fv/F0) and the maximum quantum yield of PS II (Fv/Fm), but the inhibition of the initial slope (alpha), the maximum photosynthetic rate (ETRmax) and the semi-light saturation point (Ik) increased with the increase of SPM concentration. Fv/F0, ETRmax, and Ik of C. pyrenoidosa showed some degree of recovery after inhibition in the presence of SPM of different particle sizes.

Criteria for classification, nomenclature, and reference sequence selection for HIV sub-subtypes of CRF01_AE and CRF07_BC strains in China.

The available knowledge regarding classification, nomenclature, and reference sequence selection for the various sub-subtypes of circulating recombinant forms (CRFs) is inadequate to fulfill the growing demands of research focused on HIV prevention. We analyzed the spread of CRF01_AE and CRF07_BC strains, mainly in China, to complement and update the existing nomenclature and to propose a reference sequence selection criteria for sub-subtypes of CRFs.

Comparison of the efficacy of steroid-free versus classic steroid-containing regimens in primary membranous nephropathy.

Objective: To compare the efficacy of a steroid-free regimen with steroid-based treatment in managing primary membranous nephropathy (PMN) and investigate the potential benefits of steroid-free regimens in PMN therapy. Methods: This was a single-centre prospective cohort study. A total of 81 patients were divided into two groups according to their medication regimen: a rituximab (RTX)/tacrolimus (TAC) group (low-dose RTX combined with low-dose TAC group, without steroids, n = 31) and a prednisone (P)/TAC group (P combined with TAC group, n = 61). The changes in 24-h urine protein quantification, levels of blood albumin, blood creatinine, total cholesterol, triglyceride and fasting blood glucose as well as anti-phospholipase A2 receptor antibody titres were observed in both groups before treatment and after 1, 3, 6 and 12 months of treatment. Clinical remission (complete and partial remission), serological remission and recurrence were assessed in both groups after treatment, and the occurrence of adverse reactions was observed. Results: 1) Before treatment, there was no significant difference in baseline values between the two groups (p > 0.05). 2) After 12 months of treatment, the 24-h proteinuria and total cholesterol levels in the RTX/TAC group were significantly lower than those in the P/TAC group (p < 0.05). 3) After 6 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). After 12 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). (4) After 3, 6 and 12 months of treatment, serological remission rates in the RTX/TAC group were significantly higher than those in the P/TAC group (p < 0.05). During treatment, the anti-PLA2R antibody titres in the RTX/TAC group remained lower than those in the P/TAC group (p < 0.05). Conclusion: The low-dose RTX combined with low-dose TAC steroid-free regimen induces serological remission in patients with PMN earlier than the classic regimen of P combined with TAC, and there was no significant difference in adverse effects between the two groups. Besides, the long-term clinical remission effect of low-dose RTX combined with low-dose TAC is better than that of P combined with TAC.

Distinct genetic clusters in HIV-1 CRF01_AE-infected patients induced variable degrees of CD4+ T-cell loss.

CRF01_AE strains have been shown to form multiple transmission clusters in China, and some clusters have disparate pathogenicity in Chinese men who have sex with men. This study focused on other CRF01_AE clusters prevalent in heterosexual populations. The CD4+ T-cell counts from both cross-section data in National HIV Molecular Epidemiology Survey and seropositive cohort data were used to evaluate the pathogenicity of the CRF01_AE clusters and other HIV-1 sub-types. Their mechanisms of pathogenicity were evaluated by co-receptor tropisms, predicted by genotyping and confirmed with virus isolate phenotyping, as well as inflammation parameters. Our research elucidated that individuals infected with CRF01_AE clusters 1 and 2 exhibited significantly lower baseline CD4+ T-cell counts and greater CD4+ T-cell loss in cohort follow-up, compared with other HIV-1 sub-types and CRF01_AE clusters. The increased pathogenesis of cluster 1 or 2 was associated with higher CXCR4 tropisms, higher inflammation/immune activation, and increased pyroptosis. The protein structure modeling analysis revealed that the envelope V3 loop of clusters 1 and 2 viruses is favorable for CXCR4 co-receptor usage. Imbedded with the most mutating reverse transcriptase, HIV-1 is one of the most variable viruses. CRF01_AE clusters 1 and 2 have been found to have evolved into more virulent strains in regions with predominant heterosexual infections. The virulent strains increased the pressure for early diagnosis and treatment in HIV patients. To save more lives, HIV-1 surveillance systems should be upgraded from serology and genotyping to phenotyping, which could support precision interventions for those infected by virulent viruses. IMPORTANCE: Retroviruses swiftly adapt, employing error-prone enzymes for genetic and phenotypic evolution, optimizing survival strategies, and enhancing virulence levels. HIV-1 CRF01_AE has persistently undergone adaptive selection, and cluster 1 and 2 infections display lower counts and fast loss of CD4+ T cells than other HIV-1 sub-types and CRF01_AE clusters. Its mechanisms are associated with increased CXCR4 tropism due to an envelope structure change favoring a tropism shift from CCR5 to CXCR4, thereby shaping viral phenotype features and impacting pathogenicity. This underscores the significance of consistently monitoring HIV-1 genetic evolution and phenotypic transfer to see whether selection bias across risk groups alters the delicate balance of transmissible versus toxic trade-offs, since virulent strains such as CRF01_AE clusters 1 and 2 could seriously compromise the efficacy of antiviral treatment. Only through such early warning and diagnostic services can precise antiviral treatments be administered to those infected with more virulent HIV-1 strains.

HBV promotes its replication by up-regulating RAD51C gene expression.

Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), pegylated-interferon-α(PEG-IFNα) and long-term nucleos(t)ide analogs (NUCs) are mainly drugs used to treat HBV infection, but the effectiveness is unsatisfactory in different populations, the exploration of novel therapeutic approaches is necessary. RAD51C is associated with DNA damage repair and plays an important role in the development and progression of tumors. Early cDNA microarray results showed that RAD51C expression was significantly increased in HBV-infected HCC cells, however, the relationship between HBV infection and abnormal expression of RAD51C has not been reported. Therefore, we conducted RT-PCR, western blot, Co-immunoprecipitation(Co-IP), and immunofluorescence(IF) to detect HBV-RAD51C interaction in RAD51C overexpression or interfering HCC cells. Our results showed that RAD51C and HBV X protein(HBX) produced a direct interaction in the nucleus, the HBV infection of HCC cells promoted RAD51C expression, and the increased expression of RAD51C promoted HBV replication. This indicated that RAD51C is closely related to the occurrence and development of HCC caused by HBV infection, and may bring a breakthrough in the the prevention and treatment study of HCC.

Dopant effect on the optical and thermal properties of the 2D organic-inorganic hybrid perovskite (HDA)2PbBr4.

Lead-based two-dimensional organic-inorganic hybrid perovskites (2D HOIPs) are popular materials with various optical properties, which can be tuned through metal ion doping. Due to the size and valence misfit, metal ion dopants in 2D lead-based HOIPs are still limited. In this work, Mn2+, Sb3+ and Bi3+ are doped into 2D (HDA)2PbBr4 (HDA = protonated dopamine) successfully. As a result, the dopants in 2D (HDA)2PbBr4 can induce their characteristic optical spectra, which is studied at different temperatures and excitation powers. The temperature-dependent energy transfer in the Mn-doped sample has been clarified, in which abnormal phenomena including negative thermal quenching have been observed. In addition, the dopant ions can impact the phase transition temperatures of the samples, especially lowering their crystallization temperatures greatly. The mussel-inspired organic cation, feasible metal ion regulation, and superior stability provide (HDA)2PbBr4 potential for further applications.

The efficacy and safety of direct oral anticoagulants compared with vitamin K antagonist in patients with hypertrophic cardiomyopathy and atrial fibrillation.

BACKGROUND: The benefit-risk profile of direct oral anticoagulants (DOAC) therapy in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) has not been well established yet. This study aimed to evaluate the efficacy and safety of DOAC compared with vitamin K antagonists (VKA) in patients with HCM and AF. METHODS: PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov were searched to identify studies comparing DOAC with VKA in patients with HCM and AF. The primary endpoint was thromboembolic events. The relative risks and standard errors were pooled by random-effect models using the generic inverse variance method. RESULTS: Seven observational studies involving 9395 patients were included in this meta-analysis. Compared to the VKA group, the DOAC group displayed a similar risk of thromboembolic events [RR (95%CI): 0.93 (0.73-1.20), p = 0.59] and ischemic stroke [RR (95%CI): 0.65 (0.33-1.28), p = 0.22]. The incidence of major bleeding was comparable between the two groups [RR (95%CI): 0.75 (0.49-1.15), p = 0.19]. Meanwhile, DOAC therapy was superior to VKA therapy in reducing the incidences of all-cause death [RR (95%CI): 0.44 (0.35-0.55), p < 0.001], cardiovascular death [RR (95%CI): 0.41 (0.22-0.75), p = 0.004], and intracranial hemorrhage [RR (95%CI): 0.42 (0.24-0.74), p = 0.003]. CONCLUSION: In patients with HCM and AF, DOAC therapy was similar to VKA therapy in reducing the risk of thromboembolic events, without increasing bleeding risk. In addition, the DOAC group displayed significant advantages in reducing mortality and intracranial hemorrhage compared with the VKA group. Further randomized controlled trials are needed to provide more evidence for DOAC therapy in this population.

Red cell membrane-coating Prussian blue for combined photothermal and NO gas therapy for nasopharyngeal carcinoma.

Nitric oxide (NO) gas molecules have demonstrated remarkable anti-tumor effects and minimal susceptibility to drug resistance, establishing as a promising modality for effective tumor treatment. However, how to realize its stable and efficient delivery in vivo is still a challenge. In this study, we have developed a heat-responsive biomimetic nano erythrocyte (M/B@R) by loading a NO donor (BNN6) onto mesoporous Prussian blue (M-PB) and subsequently enveloping them with red blood cell membranes. The preserved integrity of the red blood cell membrane (RBCm) structure could ensure its excellent biosafety, prolong its circulation time within the bloodstream and then enhance the accumulation of BNN6 at tumor sites. When M/B@R is stimulated by near-infrared light (NIR-II, 808 nm) irradiation, the nanoparticle could generate significant heat for photothermal therapy (PTT) by the characteristic NIR absorption of M-PB and then NO could also be efficiently released. The generated NO further facilitates the formation of ONOO-, a highly toxic species to tumors, while also alleviating tumor hypoxia. Remarkably, M/B@R, with NIR as the excitation source, induces combined lethality through hyperthermia, DNA damage, and tumor hypoxia relief. This novel combination strategy provides a new avenue for PTT/NO-induced cancer therapy.

Impact of hemoglobin adducts of ethylene oxide on the prevalence and prognosis of chronic kidney disease in US adults: an analysis from NHANES 2013-2016.

Animal experiments have shown that high exposure to ethylene oxide (EO) can cause multiple system damages including the renal system. Recent studies have reported associations between exposure to EO and cancer, dyslipidemia, diabetes, and cardiovascular disease. However, the impact of exposure to EO on the prevalence and prognosis of chronic kidney disease (CKD) in humans is scarcely investigated. The study was designed to investigate the associations between EO exposure and incidence and prognosis of CKD among 2900 US adults. Exposure to EO was measured by detecting the levels of hemoglobin adducts of EO (HbEO). The diagnosis of CKD was made according to an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) > 30 mg/g. Prognosis of CKD was assessed based on the evaluation system initiated by KDIGO that consists of eGFR and UACR. Survey-weighted generalized linear models and proportional odds models were constructed to assess the associations between HbEO and prevalence and prognosis of CKD, with odds ratios (ORs) and proportional odds ratios (PORs) and their 95% confidence intervals (CIs) reported, respectively. Restricted cubic spline (RCS) function was performed to depict the correlation between HbEO and CKD. The weighted median (interquartile range) of HbEO was 31.3 (23.1-60.3) pmol/g Hb. A total of 491 participants (16.9%) were diagnosed with CKD, and 153 participants (5.31%) were identified to be at high or very high risk. Referred to the first tertile of HbEO, the adjusted ORs (95% CIs) for CKD in the second and third tertile were 1.46 (0.85, 2.50) and 1.69 (1.00, 2.85), and the adjusted PORs (95% CIs) for prognosis of CKD in the second and third tertile were 1.37 (0.94, 1.99) and 1.58 (1.10, 2.26). When HbEO was analyzed as a continuous variable, the adjusted OR (95% CI) for CKD and POR (95% CI for prognosis of CKD were 1.24 (0.97, 1.58) and 1.22 (1.01, 1.47), respectively. RCS analysis revealed a non-linear positive correlation between HbEO and prevalence of CKD (P for nonlinearity < 0.05). Subgroup analysis indicated smoking status had a significant impact on this association, which remained significant among never smokers but lost significance among smokers. Among US adults, increased EO exposure was independently related to increased CKD prevalence and poor CKD outcomes, which was established in never smokers but not among ever smokers.

Real-time, random-access organ screening for carbapenem-resistant organisms (CRO) reduces CRO-associated, donor-derived infection mortality in lung transplant recipients.

PURPOSE: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. METHODS: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. RESULTS: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). CONCLUSION: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.

Forces driving transposable element load variation during Arabidopsis range expansion.

Genetic load refers to the accumulated and potentially life-threatening deleterious mutations in populations. Understanding the mechanisms underlying genetic load variation of transposable element (TE) insertion, a major large-effect mutation, during range expansion is an intriguing question in biology. Here, we used 1,115 global natural accessions of Arabidopsis (Arabidopsis thaliana) to study the driving forces of TE load variation during its range expansion. TE load increased with range expansion, especially in the recently established Yangtze River basin population. Effective population size, which explains 62.0% of the variance in TE load, high transposition rate, and selective sweeps contributed to TE accumulation in the expanded populations. We genetically mapped and identified multiple candidate causal genes and TEs, and revealed the genetic architecture of TE load variation. Overall, this study reveals the variation in TE genetic load during Arabidopsis expansion and highlights the causes of TE load variation from the perspectives of both population genetics and quantitative genetics.

HIV transmission and associated factors under the scale-up of HIV antiretroviral therapy: a population-based longitudinal molecular network study.

OBJECTIVES: To evaluate the prevention efficacy of scaling up HIV/AIDS antiretroviral therapy (ART) on HIV transmission at the population level and determine associated factors of HIV secondary transmission. METHODS: We used HIV longitudinal molecular networks to assess the genetic linkage between baseline and newly diagnosed cases. A generalized estimating equation was applied to determine the associations between demographic, clinical characteristics and HIV transmission. RESULTS: Patients on ART had a 32% lower risk of HIV transmission than those not on ART. A 36% reduction in risk was also seen if ART-patients maintained their HIV viral load lower than 50 copies/mL. A 71% lower risk occurred when patients sustained ART for at least 3 years and kept HIV viral load less than 50 copies/mL. Patients who discontinued ART had a similar HIV transmission risk as those not on ART. Patients who were older, male, non-Han, not single, retired, infected via a heterosexual route of transmission and those who possessed higher CD4 counts had a higher risk of HIV transmission. HIV-1 subtype of CRF01_AE was less transmissible than other subtypes. CONCLUSIONS: The efficacy of ART in a real-world setting was supported by this longitudinal molecular network study. Promoting adherence to ART is crucial to reduce HIV transmission.

Distribution pattern, molecular transmission networks, and phylodynamic of hepatitis C virus in China.

In China, few molecular epidemiological data on hepatitis C virus (HCV) are available and all previous studies were limited by small sample sizes or specific population characteristics. Here, we report characterization of the epidemic history and transmission dynamics of HCV strains in China. We included HCV sequences of individuals belonging to three HCV surveillance programs: 1) patients diagnosed with HIV infection at the Beijing HIV laboratory network, most of whom were people who inject drugs and former paid blood donors, 2) men who have sex with men, and 3) the general population. We also used publicly available HCV sequences sampled in China in our study. In total, we obtained 1,603 Ns5b and 865 C/E2 sequences from 1,811 individuals. The most common HCV strains were subtypes 1b (29.1%), 3b (25.5%) and 3a (15.1%). In transmission network analysis, factors independently associated with clustering included the region (OR: 0.37, 95% CI: 0.19-0.71), infection subtype (OR: 0.23, 95% CI: 0.1-0.52), and sampling period (OR: 0.43, 95% CI: 0.27-0.68). The history of the major HCV subtypes was complex, which coincided with some important sociomedical events in China. Of note, five of eight HCV subtype (1a, 1b, 2a, 3a, and 3b), which constituted 81.8% HCV strains genotyped in our study, showed a tendency towards decline in the effective population size during the past decade until present, which is a good omen for the goal of eliminating HCV by 2030 in China.