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Background: Positive anti-ribonucleoprotein antibodies may characterize a subgroup of patients affected by lupus nephritis with mild kidney damage, but little is known about their clinical features and long-term prognosis., Methods: Patients were retrospectively selected from the lupus nephritis database ( http://ln.medidata.cn ) of the First Affiliated Hospital of Sun Yat-sen University between 2006 and 2011. Logistic regression analysis identified the clinicopathological indicators related to positive anti-ribonucleoprotein antibodies. Additionally, the Cox proportional hazard regression model was used to assess the association of baseline variables with clinical outcomes., Results: Of the 485 enrolled patients, 184 (37.9%) tested positive for anti-ribonucleoprotein antibodies. The group with positive anti-ribonucleoprotein antibodies exhibited a higher prevalence of rash, photosensitivity, and Raynaud's phenomenon, and lower scores on the systemic lupus erythematosus disease activity index (SLEDAI) and the Activity Index scores in kidney biopsies. It is important to note that, although proteinuria did not differ, patients with anti-ribonucleoprotein positivity had a lower prevalence of hematuria and cylindruria, and a higher estimated glomerular filtration rate than patients without anti-ribonucleoprotein antibodies. After a median follow-up of approximately 170 months, no significant differences were observed in kidney or patient survival between groups., Conclusions: Lupus nephritis patients with anti-ribonucleoprotein antibodies present milder kidney damage and more dermatological manifestations. Despite the negative correlation between anti-ribonucleoprotein antibodies and both SLEDAI and activity index scores, these antibodies may not be predictive of better kidney outcomes., Competing Interests: Declarations. Conflict of interest: All the authors declared no competing interests. Ethical approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). All study participants provided signed informed consents. Statement of human and animal rights: All procedures were approved by the Human Ethics Committees of Sun Yat-sen University. Consent for publication: Not applicable., (© 2025. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Objectives: Proliferative lupus nephritis (LN) is not uncommon in individuals with proteinuria < 0.5 g/24h, highlighting the importance of predicting proliferative nephritis for effective clinical management. We aimed to develop a predictive model for proliferative nephritis in this population., Methods: The enrolled 671 biopsy-proven LN patients were divided into low-level proteinuria (< 0.5 g/24 h) and high-level proteinuria (≥ 0.5 g/24 h) groups. The clinical features, pathological characteristics and long-term outcomes of the two groups were compared. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis were used to construct a predictive nomogram for proliferative nephritis in low-level proteinuria patients and internal validation was performed using bootstrap-resampling., Results: 103 of 671 (15.4%) LN patients had low-level proteinuria, while 43 (41.7%) of whom showed proliferative LN, and the activity index and chronicity index were 5 (IQR [4,7]) and 3 (IQR [2,4]), respectively. The long-term adverse renal events-free survival was preferable in the low-level proteinuria group. The LASSO-logistic regression identified that age, sex, mean arterial pressure, haemoglobin, platelet, 24-h proteinuria and anti-double strands DNA antibodies positivity were associated with proliferative nephritis in those with low-level proteinuria. The predictive model showed an area under curve of 0.900 (95% CI: 0.840-0.960) and a bootstrapped result of 0.894 (95% CI: 0.832-0.965), with good calibration., Conclusion: 41.7% of the patients with low-level proteinuria exhibited proliferative LN when biopsied. The nomogram including clinical, urinary, and laboratory parameters might help with the prediction of proliferative LN before biopsy among patients with low-level proteinuria., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Limited research has explored the connection between consuming dietary probiotics in the diet and cancer-related deaths. This study aimed to examine how the intake levels of three different groups of dietary probiotics are associated with the risk of dying from cancer in a representative sample of adults in the United States. Using data from the USDA Food Survey Nutrient Database, researchers categorized foods based on their microbial levels as low (10 4  CFU/g), medium (10 4 -10 7  CFU/g), or high (> 10 7  CFU/g). They then used Cox proportional risk regression models to assess the risk of cancer-specific death, with follow-up periods until December 31, 2019. The study included 36,894 participants aged 20 and older, representing 148,639,331 U.S. citizens. After adjusting for various factors, the results showed that low and moderate intake of probiotics significantly reduced the risk of cancer mortality, with no significant association found for high probiotic intake. The findings suggest a notable link between dietary probiotics and cancer-specific mortality, highlighting the potential impact of dietary choices on cancer survival and indicating areas for healthcare interventions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics statement: These studies involving humans have been approved by the Ethics Review Board of the National Center for Health Statistics. The studies were conducted in accordance with local legislation and institutional requirements. According to national legislation and institutional requirements, participants or their legal guardians/next of kin do not require written informed consent., (© 2024. The Author(s).)

Background and Hypothesis: Membranous lupus nephritis (MLN) traditionally includes class V (alone) and may be associated with other classes (III or IV). The clinical, therapeutic and prognosis relevance of the classification remains controversial., Methods: A retrospective cohort of 412 MLN patients from the First Affiliated Hospital of Sun-Yat Sen University was followed for a median of 65.68 (IQR: 23.13-131.70) months. The primary outcomes were adverse renal events including all-cause death and end-stage renal diseases (ESRD). Phenotypes were identified and validated using unsupervised clustering analysis (K-means), Principal component analysis (PCA) and decision tree analysis., Results: Distinct clinical and pathological differences were noted for the traditional Class IV + V, the traditional Class V + III and Class V exhibited high similarities in clinical features and prognosis (P = 0.074). K-means clustering revealed high-risk (n = 180) and low-risk groups (n = 232), with significant differences in adverse renal outcomes (9.2% vs. 4.1%, P < 0.001). To recognize the high-risk profile of MLN patients, a decision tree based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Score, hemoglobin, serum creatinine, traditional classification, and activity index of renal biopsy accurately clustered patients in the development (95.8% accuracy) and validation (87.1% accuracy) cohorts., Conclusions: Two novel phenotypic clusters, more predictive than traditional classifications, enhance high-risk profile identification and prognostic accuracy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: No studies have explored the long-term outcomes of neural cell adhesion molecule 1 (NCAM1)-associated membranous lupus nephritis (MLN) patients., Method: We performed immunohistochemical studies on kidney biopsy specimens against NCAM1 in consecutive MLN patients. The clinical and histopathological characteristics and outcomes of cases of NCAM1-associated MLN patients are described and compared with NCAM1-negative patients. In addition, we detected serum circulating anti-NCAM1 antibodies through western blotting and indirect immunofluorescence assays., Results: Among 361 MLN cases, 18 (5.0%) were glomerular NCAM1-positive. NCAM1-positive MLN patients were older [35 years (interquartile range, IQR 27-43) versus 28 (22-37); P = .050] and had lower systemic lupus erythematosus disease activity index [11 (IQR 8-12) versus 14 (10-18); P = .007], serum creatinine [60 μmol/L (IQR 50-70) versus 70 (54-114); P = .029] and activity index [3 (IQR 2-6) versus 6 (3-9); P = .045] at kidney biopsy compared with NCAM1-negative patients. The percentage of positive anti-Sjögren's syndrome-related antigen A antibodies in NCAM1-positive patients was significantly greater (83.3% versus 58.2%; P = .035) than in the NCAM1-negative patients. However, no evidence of neuropsychiatric disorders was found in these 18 patients. There were no significant differences in the treatment response and the risk of end-stage renal diseases between NCAM1-positive and -negative groups (P = .668 and P = .318, respectively). However, the risk of death was much higher in the NCAM1-positive group than the NCAM1-negative group (27.8% vs 8.1%; P = .007). Moreover, the risk of death was also much higher in the NCAM1-positive group than the matched NCAM1-negative group (Log-rank P = .013). Additionally, circulating anti-NCAM1 antibodies can be detected in 1/5 (20%) patients who had serum available., Conclusion: The prevalence of NCAM1 positivity was 5.0% in our cohort of MLN and the high mortality in these subgroup patients are needed to validate in future studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Purpose: For unexpected low-prognosis patients (Group 1 and Group 2) defined by POSEIDON criteria, how to maximize the live birth rate while controlling the multiple birth rate by tailoring the embryo transfer number and quality?, Methods: This was a retrospective study, including patients from Poseidon Group 1 (N = 672) and Group 2 (N = 503) who underwent cleavage-stage embryo transfer. Logistic regression was used for the comparative analysis of clinical outcomes among subgroups divided by the number and quality of embryos., Results: For Group 1, compared to transferring a single good-quality embryo (GQE), a good-quality embryo with a poor-quality embryo (GQE + PQE) did not significantly improve the live birth rate, although increasing in value (40.5% vs 31.9%, P = 0.272), meanwhile obviously raised the multiple birth rate to 28.1% (P = 0.042). For Group 2, double embryo transfer (DET) was associated with a higher live birth rate than single embryo transfer (SET) (22.4% vs 6.3%, P = 0.001) and further analysis indicated that the similar trend observed in the GQE + PQE group compared to the GQE group (26.1% vs 8.5%, P = 0.017) with statistical significance, but without a significant increase in the multiple birth rate (8.3%, P = 1.000)., Conclusions: The study indicated that  a single good-quality cleavage-stage embryo was an option for patients in Poseidon Group 1 to avoid the risk of multiple pregnancies. DET with mixed quality cleavage-stage embryo might be an alternative for Poseidon Group 2, given that it improved the pregnancy outcomes while controlling the multiple birth rates., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. Ethics approval: This study has been approved by the Ethics Review Committee of Shenzhen Hospital of Peking University. Consent to participate: Not applicable. Consent to publish: This manuscript is approved by all the authors for publication., (© 2024. The Author(s).)

Gut microbiota is important for host metabolism regulation. Antibiotic exposure disturbs this regulation by affecting the microbiome. Trace levels of antibiotics in water have been widely reported and the impact on gut microbiota remains understudied. We provide evidence of trace antibiotic exposure affecting the host's gut microbiota using a mouse model exposed to trace amounts of azithromycin (AZI) or ciprofloxacin (CIP) in drinking water. AZI exposure in males changed the distribution of gram-positive (Firmicutes and Bacteroidetes) and gram-negative (Proteobacteria, Fusobacteria, and Verrucomicrobia) bacteria at an early age. Both AZI and CIP resulted in abnormal microbiota maturation. Additionally, the production of short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, in females is affected. Serum hormone and metabolome levels shifted after trace antibiotic exposure. AZI and CIP exposure broadly disrupted original host-microbe interaction relationships between the gut microbiota and SCFAs or serum metabolites. In this study, we demonstrated that trace antibiotic exposure was associated with extensive gut microbiota and metabolism perturbation in mice and that the potential health risks in susceptible populations should be considered., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Little evidence is available on the long-term health effects of nitrogen dioxide (NO 2 ) in low-income and middle-income populations. We investigated the associations of long-term NO 2 exposure with the incidence of a wide spectrum of disease outcomes, based on data from the China Kadoorie Biobank., Methods: This prospective cohort study involved 512 724 Chinese adults aged 30-79 years recruited from ten areas of China during 2004-08. Time-varying Cox regression models yielded adjusted hazard ratios (HRs) for the associations of long-term NO 2 exposure with aggregated disease incidence endpoints classified by 14 ICD-10 chapters, and incidences of 12 specific diseases selected from three key ICD-10 chapters (cardiovascular, respiratory, and musculoskeletal diseases) found to be robustly associated with NO 2 in the analyses of aggregated endpoints. All models were stratified by age-at-risk (in 1-year scale), study area, and sex, and were adjusted for education, household income, smoking status, alcohol intake, cooking fuel type, heating fuel type, self-reported health status, BMI, physical activity level, temperature, and relative humidity., Findings: The analysis of 512 709 participants (mean baseline age 52·0 years [SD 10·7]; 59·0% female and 41·0% male) included approximately 6·5 million person-years of follow-up. Between 5285 and 144 852 incident events were recorded for each of the 14 aggregated endpoints. Each 10 μg/m 3 higher annual average NO 2 exposure was associated with higher risks of chapter-specific endpoints, especially cardiovascular (n=144 852; HR 1·04 [95% CI 1·02-1·05]), respiratory (n=73 232; 1·03 [1·01-1·05]), musculoskeletal (n=54 409; 1·11 [1·09-1·14]), and mental and behavioural (n=5361; 1·12 [1·05-1·21]) disorders. Further in-depth analyses on specific diseases found significant positive supra-linear associations with hypertensive disease (1·08 [1·05-1·11]), lower respiratory tract infection (1·03 [1·01-1·06]), arthrosis (1·15 [1·09-1·21]), intervertebral disc disorders (1·13 [1·09-1·17]), and spondylopathies (1·05 [1·01-1·10]), and linear associations with ischaemic heart disease (1·03 [1·00-1·05]), ischaemic stroke (1·08 [1·06-1·11]), and asthma (1·15 [1·04-1·27]), whereas intracerebral haemorrhage (1·00 [0·95-1·06]), other cerebrovascular disease (0·98 [0·96-1·01]), acute upper respiratory infection (1·03 [0·96-1·09]), and chronic lower respiratory disease (0·98 [0·95-1·02]) showed no significant association. NO 2 exposure showed robust null association with external causes (n=32 907; 0·98 [0·95-1·02]) as a negative control., Interpretation: In China, long-term NO 2 exposure was associated with a range of diseases, particularly cardiovascular, respiratory, and musculoskeletal diseases. These associations underscore the pressing need to implement the recently tightened WHO air quality guidelines., Funding: Wellcome Trust, UK Medical Research Council, Cancer Research UK, British Heart Foundation, National Natural Science Foundation of China, National Key Research and Development Program of China, Sino-British Fellowship Trust, and Kadoorie Charitable Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

A convenient and sustainable method for synthesizing sulfonyl-containing compounds through a catalyst-free aqueous-phase hydrosulfonylation of alkenes and alkynes with sulfonyl chlorides under visible light irradiation is presented. Unactivated alkenes, electron-deficient alkenes, alkyl and aryl alkynes can be hydrosulfonylated with various sulfonyl chlorides at room temperature with excellent yields and geometric selectivities by using tris(trimethylsilyl)silane as a hydrogen atom donor and silyl radical precursor to activate sulfonyl chlorides. Mechanistic studies revealed that the photolysis of tris(trimethylsilyl)silane in aqueous solution to produce silyl radical is crucial for the success of this reaction., (© 2024 Wiley-VCH GmbH.)

Rectal neuroendocrine neoplasms (rNENs) are among the most frequent gastrointestinal neuroendocrine neoplasms and pose a serious challenge for clinical management. The size of the primary neoplasm is considered to be the most important predictor of disease progression, but the genetic alterations that occur during the progression of rNENs remain unknown. Here, we performed a comprehensive whole-exome sequencing study on 54 tumor-normal paired, formalin-fixed paraffin-embedded specimens from patients locally diagnosed with rNENs. Of these, 81.5% (n = 44) were classified as small-sized (≤2 cm) rNENs, while the remainder (18.5%, n = 10) were classified as large-sized (>2 cm) rNEN samples. Comparative analysis revealed marked disparities in the mutational landscape between small- and large-sized rNEN samples, and between large-sized rNEN samples with or without lymph node metastases. The high-confidence driver genes RHPN2, MUC16, and MUC4 were significantly mutated in both small- and large-sized rNEN specimens, whereas mutations in MAN2A1, and BAG2 were only identified in large-sized specimens diagnosed with lymph node metastases. Correspondingly, we observed that the mTOR and MAPK pathways were preferentially enriched in the large-sized rNEN specimens. Signature-based analysis revealed that mutational processes associated with defective DNA base excision repair (SBS30) significantly accumulated in large-sized rNEN samples with lymph node metastases, highlighting the important role of this mutagenic process in promoting rNEN progression. We further found that most rNEN subjects, regardless of tumor size, harbored at least one alteration with targeted therapeutic implications. Taken together, these results elucidate the genetic features associated with tumor size and lymphatic metastasis in rNEN patients, which will deepen our understanding of the genetic changes during rNEN progression and potentially directing improvements in rNEN treatment strategies., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To evaluate the prognostic importance of sex in lupus nephritis (LN)., Methods: A retrospective cohort of 1048 biopsy-confirmed LN patients, diagnosed between January 1, 1996, and December 31, 2018, was analyzed. Demographics, clinical characteristics, laboratory findings, and renal pathology were assessed. The primary outcome was mortality, and the secondary outcomes included doubling of serum creatinine and end-stage renal disease (ESRD). Sex-associated risks were evaluated using Cox regression models., Results: Among the1048 patients, 178 (17%) were male and 870 (83%) were female. Male patients exhibited more aggressive features: higher blood pressure, earlier disease onset, and elevated levels of serum creatinine (Scr), uric acid, blood urea nitrogen. Intriguingly, male patients also displayed more severe histopathological alterations, such as more total crescents, cellular crescents formations, higher level of glomerular leukocyte infiltration and Activity Index (AI), even when overall renal pathology was comparable between sexes. During a median follow-up of 112 months, mortality was registered in 141 patients (15.3%). Mortality rates were conspicuously higher in males (24.2% males vs. 13.4% females, p = 0.0029). Secondary outcomes did not show significant sex differences. Cox regression analysis highlighted male, age of renal biopsy, eGFR, and Chronicity Index (CI) as independent risk factors for survival in LN patients. Notably, infections emerged as the leading cause of mortality among LN patients, with a significant higher rate in male patients., Conclusion: In our cohort with LN, there was a higher rate of all-cause mortality and proportion of infection-related death in male. Recognizing and further exploring these sex disparities is crucial for optimized LN patients care., (© 2024. The Author(s).)

Non-optimal temperature is a leading risk factor for global disease burden. Most epidemiological studies assessed only outdoor temperature, with important uncertainties on personal exposure misclassification. The CKB-Air study measured personal, household (kitchen and living room), and outdoor temperatures in the summer (MAY-SEP 2017) and winter (NOV 2017-JAN 2018) in 477 participants in China. After data cleaning, ∼88,000 person-hours of data were recorded across each microenvironment. Using multivariable linear regression (MLR) and random forest (RF) models, we identified key predictors and constructed personal temperature exposure prediction models. We used generalised additive mixed effect models to examine the relationships of personal and outdoor temperatures with heart rate. The 24-hour mean (SD) personal and outdoor temperatures were 29.2 (3.8) °C and 27.6 (6.4) °C in summer, and 12.0 (4.0) °C and 7.5 (4.2) °C in winter, respectively. The temperatures across microenvironments were strongly correlated (Spearman's ρ: 0.86-0.92) in summer. In winter, personal temperature was strongly related to household temperatures (ρ: 0.74-0.79) but poorly related to outdoor temperature (ρ: 0.30). RF algorithm identified household and outdoor temperatures and study date as top predictors of personal temperature exposure for both seasons, and heating-related factors were important in winter. The final MLR and RF models incorporating questionnaire and device data performed satisfactorily in predicting personal exposure in both seasons (R 2 summer : 0.92; R 2 winter : 0.68-0.70). We found consistent U-shaped associations between measured and predicted personal temperature exposures and heart rate (lowest at ∼ 14.5 °C), but a weak positive linear association with outdoor temperature. Personal and outdoor temperatures differ substantially winter, but prediction models incorporating household and outdoor temperatures and questionnaire data performed satisfactorily. Exposure misclassification from using outdoor temperature may produce inappropriate epidemiological findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Gastric adenocarcinoma of the fundic gland type (GA-FG) is a newly described variant of gastric adenocarcinoma with lack of knowledges regarding its genetic features., Methods: We performed whole-genome sequencing (WGS) in formalin-fixed paraffin-embedded (FFPE) tumor tissues and matched adjacent noncancerous specimens from 21 patients with GA-FG, and integrated published datasets from 1105 patients with traditional gastric adenocarcinoma with the purpose of dissecting genetic determinants both common to conventional gastric adenocarcinoma and unique to GA-FG disease., Results: We characterized the genomic architecture of GA-FG disease, revealing the predominant proportion of C > T substitution among the six types of SNVs. GNAS was the most significantly mutated driver gene (14.29%). 42.8% of samples harbored "Kataegis." Distinct genomic alterations between GA-FG and conventional gastric cancer were identified. Specifically, low mutational burden and relatively moderate mutational frequencies of significantly mutated driver genes, coupled with the absence of non-silent alterations of formerly well-known drivers such as TP53, PIK3CA and KRAS were identified in GA-FG patients. Oncogenic signaling pathway analysis revealed mutational processes associated with focal adhesions and proteoglycans in cancer, highlighting both common and specific procedures during the development of GA-FG and conventional gastric cancer., Conclusion: Our study is the first to comprehensively depict the genomic landscape highlighting the multidimensional perturbations in GA-FG patients. These discoveries offered mechanistic insights for novel diagnostic and therapeutic strategies for patients with such disease., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Magnaporthe oryzae is a devastating fungal pathogen that causes the rice blast disease worldwide. The post-translational modification of ADP-ribosylation holds significant importance in various fundamental biological processes. However, the specific function of this modification in M. oryzae remains unknown. This study revealed that Poly(ADP-ribosyl)ation (PARylation) executes a critical function in M. oryzae. M. oryzae Poly(ADP-ribose) polymerase 1 (PARP1) exhibits robust PARylation activity. Disruption of PARylation by PARP1 knock-out or chemical inhibition reveals its involvement in M. oryzae virulence, particularly in appressorium formation. Furthermore, we identified two M. oryzae 14-3-3 proteins, GRF1 and GRF2, as substrates of PARP1. Deletion of GRF1 or GRF2 results in delayed and dysfunctional appressorium, diminished plant penetration, and reduced virulence of the fungus. Biochemical and genetic evidence suggest that PARylation of 14-3-3s is essential for its function in M. oryzae virulence. Moreover, PARylation regulates 14-3-3 dimerization and is required for the activation of the mitogen-activated protein kinases (MAPKs), Pmk1 and Mps1. GRF1 interacts with both Mst7 and Pmk1, and bridges their interaction in a PARylation-dependent manner. This study unveils a distinctive mechanism that PARylation of 14-3-3 proteins controls appressorium formation through MAPK activation, and could facilitate the development of new strategies of rice blast disease control., (© 2024. The Author(s).)

Background and Objectives: This study aimed to assess the prevalence, predictors, and outcomes of pulmonary hypertension (PH) in patients with lupus nephritis (LN). Materials and Methods: Baseline characteristics and clinical outcomes of 387 patients with LN were retrospectively collected from 2007 to 2017. PH was defined as pulmonary artery systolic pressure ≥40 mmHg assessed by resting transthoracic echocardiography. The primary endpoint was all-cause mortality. The secondary endpoint was renal events, defined as the doubling of baseline serum creatinine or end-stage renal disease. Associations between PH and outcomes were analyzed by Cox regression models. Results: A total of 15.3% (59/387) of patients with LN were diagnosed with PH, and the prevalence of PH was higher for patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m 2 compared to those with an eGFR ≥ 30 mL/min/1.73 m 2 (31.5% vs. 12.6%). Higher mean arterial pressure, lower hemoglobin, and lower triglyceride levels were associated with greater odds of having PH. After adjusting for relevant confounding variables, PH was independently associated with a higher risk for death (HR: 2.01; 95% CI: 1.01-4.00; p = 0.047) and renal events (HR: 2.07; 95% CI: 1.04-4.12; p = 0.039). Conclusions: PH is an independent risk factor for all-cause mortality and adverse renal outcomes in patients with LN.

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6 + ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The 2016 Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria redefined the poor responders as low prognosis patients. The embryo transfer strategy for POSEIDON patients remained to be addressed. This study aimed to investigate the optimized number of embryos to transfer for unexpected low-prognosis patients (POSEIDON Group 1 and Group 2) with blastocyst transfer in their first frozen cycle., Methods: A retrospective cohort study of 2970 patients who underwent frozen-thawed embryo transfer (FET) between January 2018 and December 2021. Patients from POSEIDON Group 1 (N = 219) and Group 2 (N = 135) who underwent blastocyst transfer in their first FET cycles were included and divided into the elective single embryo transfer (eSET) group and the double embryo transfer (DET) group., Results: For POSEIDON Group 1, the live birth rate per embryo transfer of the DET group was slightly higher than the eSET group (52.17% vs 46.15%, OR 0.786, 95% CI 0.462-1.337, P = 0.374; adjusted OR (aOR) 0.622, 95% CI 0.340-1.140, P = 0.124), while a significant increase of 20.00% in the multiple birth rate was shown. For Group 2, higher live birth rates were observed in the DET group compared to the eSET group (38.46% vs 20.48%, OR 0.412, 95% CI 0.190-0.892, P = 0.024; aOR 0.358, 95% CI 0.155-0.828, P = 0.016). The difference in the multiple birth rate was 20.00% without statistical significance. Univariate and multivariate analyses revealed that age (OR 0.759, 95% CI .624-0.922, P = 0.006 and OR 0.751, 95% CI 0.605-0.932, P = 0.009) and the number of transferred embryos (OR 0.412, 95% CI 0.190-0.892, P = 0.024 and OR 0.367, 95% CI 0.161-0.840, P = 0.018) were significant variables for the live birth rate in POSEIDON Group 2., Conclusions: The findings in the present study showed that eSET was preferred in the first frozen cycle for POSEIDON Group 1 to avoid unnecessary risks. Double embryo transfer strategy could be considered to improve the success rate for POSEIDON Group 2 with caution. Further stratification by age is needed for a more scientific discussion about the embryo transfer strategy for POSEIDON patients., (© 2024. The Author(s).)

Background: Cervical cancer is one of the most common malignancies in women worldwide. As a RING type ubiquitin ligase, SIAH2 has been reported to promote the progression of a variety of tumors by interacting with and targeting multiple chaperones and substrates. The aim of this study was to further identify the role and the related molecular mechanisms involved of SIAH2 in cervical carcinogenesis., Methods and Results: Cellular assays in vitro showed that knockdown of SIAH2 inhibited the proliferation, migration and invasion of human cervical cancer cells C33A and SiHa, induced apoptosis, and increased the sensitivity to cisplatin treatment. Knockdown of SIAH2 also inhibited the epithelial-mesenchymal transition and activation of the Akt/mTOR signaling pathway in cervical cancer cells, which were detected by Western blot. Mechanistically, SIAH2, as a ubiquitin ligase, induced the ubiquitination degradation of GSK3β degradation by using coIP. The results of complementation experiments further demonstrated that GSK3β overexpression rescued the increase of cell proliferation and invasion caused by SIAH2 overexpression. Specific expression of SIAH2 appeared in precancerous and cervical cancer tissues compared to inflammatory cervical lesions tissues using immunohistochemical staining. The more SIAH2 was expressed as the degree of cancer progressed. SIAH2 was significantly highly expressed in cervical cancer tissues (44/55, 80 %) compared with precancerous tissues (18/69, 26.1 %). Moreover, the expression level of SIAH2 in cervical cancer tissues was significantly correlated with the degree of cancer differentiation, and cervical cancer tissues with higher SIAH2 expression levels were less differentiated., Conclusion: Targeting SIAH2 may be beneficial to the treatment of cervical cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Corticosteroids remain contentious as a therapeutic option for IgA nephropathy. We conducted a retrospective cohort study to explore whether corticosteroid therapy is efficient and safe for IgAN patients with moderate proteinuria., Methods: A total of 336 patients with renal biopsy-confirmed IgAN, estimated glomerular filtration (eGFR) over 15 mL/min/1.73 m 2 and urine protein levels of 0.75-3.5 g/d were enrolled. According to the treatment protocol, we classified the enrolled patients into two groups: one receiving corticosteroids and the other receiving supportive care. Complete remission, partial remission, and no remission were applied to describe the efficacy assessments. The endpoint was defined as a 40% reduction in eGFR, the onset of ESRD, or renal disease-related death., Results: Clinical and pathological progression risk factors were higher in corticosteroid-treated individuals. Logistic regression analysis revealed that the corticosteroid group was considerably related to a higher remission rate after adjustment for confounding factors. The occurrence of serious adverse events between the two groups was not found to be statistically significantly different. Then, we matched 95 couples of patients with similar baseline levels in both groups by propensity score matching. The results showed that corticosteroid-treated patients showed higher overall and complete remission rates than untreated patients. However, due to the relatively short follow-up period, no significant differences in the incidence of endpoint and survival analyses have been observed thus far., Conclusion: Corticosteroid therapy may benefit IgAN patients with moderate proteinuria via proteinuria reduction and renal function preservation., (© 2024 Asian Pacific Society of Nephrology.)

The emergence of drug-resistant Enterobacteriaceae carrying plasmid-mediated β-lactamase genes has become a significant threat to public health. Organisms in the Enterobacteriaceae family containing New Delhi metallo-β-lactamase‑1 (NDM-1) and its variants, which are capable of hydrolyzing nearly all β-lactam antibacterial agents, including carbapenems, are referred to as superbugs and distributed worldwide. Despite efforts over the past decade, the discovery of an NDM-1 inhibitor that can reach the clinic remains a challenge. Here, we identified oxidized glutathione (GSSG) as a metabolic biomarker for bla NDM-1 using a non-targeted metabolomics approach and demonstrated that GSSG supplementation could restore carbapenem susceptibility in Escherichia coli carrying bla NDM-1 in vitro and in vivo. We showed that exogenous GSSG promotes the bactericidal effects of carbapenems by interfering with intracellular redox homeostasis and inhibiting the expression of NDM-1 in drug-resistant E. coli. This study establishes a metabolomics-based strategy to potentiate metabolism-dependent antibiotic efficacy for the treatment of antibiotic-resistant bacteria., (© 2024. The Author(s).)

Helicobacter pylori is a highly successful pathogen that poses a substantial threat to human health. However, the dynamic interaction between H. pylori and the human gastric epithelium has not been fully investigated. In this study, using dual RNA sequencing technology, we characterized a cytotoxin-associated gene A ( cagA )-modulated bacterial adaption strategy by enhancing the expression of ATP-binding cassette transporter-related genes, metQ and HP&#95;0888 , upon coculturing with human gastric epithelial cells. We observed a general repression of electron transport-associated genes by cagA , leading to the activation of oxidative phosphorylation. Temporal profiling of host mRNA signatures revealed the downregulation of multiple splicing regulators due to bacterial infection, resulting in aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. Moreover, we demonstrated a protective effect of gastric H. pylori colonization against chronic dextran sulfate sodium (DSS)-induced colitis. Mechanistically, we identified a cluster of propionic and butyric acid-producing bacteria, Muribaculaceae , selectively enriched in the colons of H. pylori -pre-colonized mice, which may contribute to the restoration of intestinal barrier function damaged by DSS treatment. Collectively, this study presents the first dual-transcriptome analysis of H. pylori during its dynamic interaction with gastric epithelial cells and provides new insights into strategies through which H. pylori promotes infection and pathogenesis in the human gastric epithelium., Importance: Simultaneous profiling of the dynamic interaction between Helicobacter pylori and the human gastric epithelium represents a novel strategy for identifying regulatory responses that drive pathogenesis. This study presents the first dual-transcriptome analysis of H. pylori when cocultured with gastric epithelial cells, revealing a bacterial adaptation strategy and a general repression of electron transportation-associated genes, both of which were modulated by cytotoxin-associated gene A ( cagA ). Temporal profiling of host mRNA signatures dissected the aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. We demonstrated a protective effect of gastric H. pylori colonization against chronic DSS-induced colitis through both in vitro and in vivo experiments. These findings significantly enhance our understanding of how H. pylori promotes infection and pathogenesis in the human gastric epithelium and provide evidence to identify targets for antimicrobial therapies., Competing Interests: The authors declare no conflict of interest.

Ambient fine particulate matter (PM 2.5 ) is a leading environmental risk factor globally, and over half of the associated disease burden are caused by cardiovascular disease. Numerous randomized controlled trials (RCT) have investigated the short-term cardiovascular benefits of indoor air purifiers (IAPs), but major knowledge gaps remain on their longer-term benefits. In this 1-year, randomized, double-blinded, parallel controlled trial of 47 elderly (n true-purification  = 24; n sham-purification  = 23) aged ≥70 years, true-purification reduced household PM 2.5 levels by 28% and maintained lower exposure throughout the year compared to the sham-purification group. After 12 months of intervention, a significant reduction of diastolic blood pressure was found in the true-purification versus sham-purification group (-4.62 [95% CI: -7.28, -1.96] mmHg) compared to baseline measurement prior to the intervention, whereas systolic blood pressure showed directionally consistent but statistically non-significant effect (-2.49 [95% CI: -9.25, 4.28] mmHg). Qualitatively similar patterns of associations were observed for pulse pressure (-2.30 [95% CI: -6.57, 1.96] mmHg) and carotid intima-media thickness (-10.0% [95% CI: -24.8%, 4.7%]), but these were not statistically significant. Overall, we found suggestive evidence of cardiovascular benefits of long-term IAPs use, particularly on diastolic blood pressure. Evidence on other longer-term cardiovascular traits is less clear. Further trials with larger sample sizes and long-term follow-up are needed across diverse populations to evaluate the cardiovascular benefits of IAPs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ka Hung Chan reports financial support was provided by BHF Centre of Research Excellence. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ketamine as a glutamate receptor antagonist has a rapid, potent, and long-lasting antidepressant effect, but its specific mechanism is still not fully understood. Depression is associated with elevated levels of glutamate and astrocyte loss in the brain; the exploration of the relationships between ketamine's antidepressant effect and astrocytes has drawn great attention. Astrocytes and aquaporin 4 (AQP4) are essential components of the glymphatic system, which is a brain-wide perivascular pathway to help transport nutrients to the parenchyma and remove metabolic wastes. In this study, we investigated pyroptosis-associated protein Nlrp3/Caspase-1/Gsdmd-N expression in the hippocampus of mice and the toxic effect of high levels of glutamate on primary astrocytes. On this basis, the protective mechanism of ketamine is explored. A single administration of ketamine (10 mg/kg) remarkably relieved anxious and depressive behaviors in the sucrose preference test, elevated plus maze test, and forced swim test. Meanwhile, ketamine reduced the level of hippocampus Nlrp3 and the expression of its downstream molecules in chronic unpredictable mild stress (CUMS) mice model by western blot and reduced the colocalization of Gfap and Gsdmd by nearly 25% via immunofluorescent staining. Ketamine also increased the Gfap-positive cells and AQP4 expression in the hippocampus of the CUMS mice. More important, ketamine increased the distribution of the fluorescent tracer of CUMS mice. Treatment with 128 mM glutamate in cortical and hippocampus astrocytes increased the level of Nlrp3, and Gsdmd-N, and ketamine alleviated high glutamate-induced pyroptosis-associated proteins. In summary, these results suggest that high glutamate-induced astrocyte pyroptosis through the Nlrp3/Caspase-1/Gsdmd-N pathway which was inhibited by ketamine and ketamine can improve the damaged glymphatic function of the CUMS mice. The present study indicates that inhibiting astrocyte pyroptosis and promoting the glymphatic circulation function are a new mechanism of ketamine's antidepressant effect, and astrocyte pyroptosis may be a new target for other antidepressant medicines., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Many patients with ulcerative colitis (UC) do not respond well to, or tolerate conventional and biological therapies. There is currently no consensus on the treatment of refractory UC. Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib, a small-molecule drug, is effective and safe for treating UC. However, no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab., Case Summary: We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus, in addition to dizziness. The patient had recurrent disease after receiving mesalazine, prednisone, azathioprine, infliximab and vedolizumab over four years. Based on the endoscopic findings and pathological biopsy, the patient was diagnosed with refractory UC. In particular, the patient showed primary nonresponse to infliximab and vedolizumab. Based on the patient's history and recurrent disease, we decided to administer upadacitinib. During hospitalisation, the patient was received upadacitinib under our guidance. Eight weeks after the initiation of upadacitinib treatment, the patient's symptoms and endoscopic findings improved significantly. No notable adverse reactions have been reported to date., Conclusion: Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Few studies have focused on the spatial distribution of the typical components and source tracers of PM 2.5 and their associated health risks, despite the fact that the chemical components of PM 2.5 pose potentially significant and independent risks to human health. The main objective of this study was to evaluate the spatial distribution of major PM 2.5 components and their associated health risks in Hong Kong using a coupled land use regression and health risk assessment modeling approach. The established land use regression models of the major PM 2.5 components and source tracers achieved a relatively high statistical performance, with training and leave-one-out cross-validation R 2 values of 0.85-0.96 and 0.62-0.88, respectively. The high spatial resolution (500 m × 500 m) distribution patterns of the chemical components of PM 2.5 showed the heterogeneity of population exposure to different components and the related potential health risks, as evidenced by the weak spatial correlations between the mass of PM 2.5 and some components. Elemental carbon, nickel, arsenic, and chromium from PM 2.5 made major contributions to the total health risk and should therefore be reduced further. Our results will enable researchers to determine independent associations between exposure to the various components of PM 2.5 and health endpoints in epidemiological studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The relationship of exostosin 1 and exostosin 2 (EXT1/EXT2) expression and outcomes in membranous lupus nephritis (MLN) was controversial., Methods: EXT1/EXT2 was performed by immunohistochemistry (IHC) in 283 consecutive patients with MLN. Clinicopathological characteristics and outcomes of EXT1/EXT2-positive patients were compared with EXT1/EXT2-negative patients. The primary end points were adverse renal events, including death, dialysis, and renal transplantation., Results: Of the patients with MLN, 29.3% were positive for EXT1/EXT2. The prevalence of EXT1/2-positive MLN was significantly higher in pure class V MLN than those for mixed class V MLN (44.2% vs. 19.4%, P  < 0.001). For EXT1/EXT2-positive patients, the median time between onset of lupus and renal biopsy, and lupus nephritis and renal biopsy is shorter (6 [interquartile range, IQR: 2-25] months vs. 12 [IQR: 3-49] months, P  = 0.008 and 3 [IQR: 2-18] months vs. 6 [IQR: 2-23] months, P  = 0.039) and they had significantly lower systemic lupus erythematosus Disease Activity Index (SLEDAI) scores ( P  = 0.015) and lower serum creatinine levels ( P  < 0.001), higher hemoglobin ( P  = 0.006) as well as lower blood pressure. The EXT1/EXT2-positive patients had significantly fewer chronicity features (glomerulosclerosis, P  < 0.001; interstitial fibrosis, P  = 0.006; and tubular atrophy, P  = 0.002) and fewer activity indicators (endocapillary hypercellularity, P  = 0.012; cellular crescents, P  = 0.007; and fibrocellular crescents, P  < 0.001) on renal biopsy. After a median follow-up of 65 (28-126) months, EXT1/EXT2-positive patients were less likely to experience adverse renal events (2.4% vs. 16.0%, P  = 0.001)., Conclusion: Compared with EXT1/EXT2-negative patients, the EXT1/EXT2-positive patients presented with lower disease activity and were less likely to experience adverse renal events in relationship with the chronicity index., (© 2024 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Background: Cooking and heating in households contribute importantly to air pollution exposure worldwide. However, there is insufficient investigation of measured fine particulate matter (PM 2.5 ) exposure levels, variability, seasonality, and inter-spatial dynamics associated with these behaviours., Methods: We undertook parallel measurements of personal, household (kitchen and living room), and community PM 2.5 in summer (May-September 2017) and winter (November 2017-Janauary 2018) in 477 participants from one urban and two rural communities in China. After stringent data cleaning, there were 67,326-80,980 person-hours (n total  = 441; n summer  = 384; n winter  = 364; 307 had repeated PM 2.5 data in both seasons) of processed data per microenvironment. Age- and sex-adjusted geometric means of PM 2.5 were calculated by key participant characteristics, overall and by season. Spearman correlation coefficients between PM 2.5 levels across different microenvironments were computed., Findings: Overall, 26.4 % reported use of solid fuel for both cooking and heating. Solid fuel users had 92 % higher personal and kitchen 24-h average PM 2.5 exposure than clean fuel users. Similarly, they also had a greater increase (83 % vs 26 %) in personal and household PM 2.5 from summer to winter, whereas community levels of PM 2.5 were 2-4 times higher in winter across different fuel categories. Compared with clean fuel users, solid fuel users had markedly higher weighted annual average PM 2.5 exposure at personal (78.2 [95 % CI 71.6-85.3] μg/m 3 vs 41.6 [37.3-46.5] μg/m 3 ), kitchen (102.4 [90.4-116.0] μg/m 3 vs 52.3 [44.8-61.2] μg/m 3 ) and living room (62.1 [57.3-67.3] μg/m 3 vs 41.0 [37.1-45.3] μg/m 3 ) microenvironments. There was a remarkable diurnal variability in PM 2.5 exposure among the participants, with 5-min moving average from 10 μg/m 3 to 700-1200 μg/m 3 across different microenvironments. Personal PM 2.5 was moderately correlated with living room (Spearman r: 0.64-0.66) and kitchen (0.52-0.59) levels, but only weakly correlated with community levels, especially in summer (0.15-0.34) and among solid fuel users (0.11-0.31)., Conclusion: Solid fuel use for cooking and heating was associated with substantially higher personal and household PM 2.5 exposure than clean fuel users. Household PM 2.5 appeared a better proxy of personal exposure than community PM 2.5 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Group 3 innate lymphoid cells (ILC3s) represent a new population in immune regulation, yet their role in lupus nephritis (LN) remains elusive. In the present work, systemic increases in ILC3s, particularly in the kidney, are observed to correlate strongly with disease severity in both human and murine LN. Using MRL/lpr lupus mice and a nephrotoxic serum-induced LN model, this study demonstrates that ILC3s accumulated in the kidney migrate predominantly from the intestine. Furthermore, intestinal ILC3s accelerate LN progression, manifested by exacerbated autoimmunity and kidney injuries. In LN kidneys, ILC3s are located adjacent to B cells within ectopic lymphoid structures (ELS), directly activating B cell differentiation into plasma cells and antibody production in a Delta-like1 (DLL1)/Notch-dependent manner. Blocking DLL1 attenuates ILC3s' effects and protects against LN. Altogether, these findings reveal a novel pathogenic role of ILC3s in B cell activation, renal ELS formation and autoimmune injuries during LN, shedding light on the therapeutic value of targeting ILC3s for LN., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: The clinicopathological features, outcomes, and pathogenesis of lupus nephritis with scanty immune deposits in the kidney biopsy remain unclear., Methods: Four hundred ninety-eight biopsy-proven lupus nephritis patients were included, and clinical and pathological data were collected. The primary endpoint was mortality, while the secondary endpoint was doubling baseline serum creatinine or end-stage renal disease. Associations between scanty immune deposits lupus nephritis and adverse outcomes were analyzed by Cox regression models., Results: Among 498 lupus nephritis patients, 81 were diagnosed with scanty immune deposits. Patients with scanty immune deposits had significantly higher serum albumin and serum complement C4 than those with immune complex deposits. The proportion of anti-neutrophil cytoplasmic antibodies was similar between the two groups. In addition, patients with scanty immune deposits showed less proliferative features at kidney biopsy and lower activity index score, accompanied by milder mesangial cell and matrix hyperplasia, endothelial cell hyperplasia, nuclear fragmentation, and glomerular leukocyte infiltration. Patients in this group also had a milder degree of foot process fusion. Overall, renal survival and patient survival showed no significant difference between the two groups. 24-h proteinuria and chronicity index were significant risk factors for renal survival, and 24-h proteinuria and positive anti-neutrophil cytoplasmic antibodies were risk factors for patient survival in scanty immune deposits lupus nephritis patients., Conclusions: Compared with other lupus nephritis patients, scanty immune deposits lupus nephritis patients had significantly lower activity features on kidney biopsy, but have similar outcomes. Positive anti-neutrophil cytoplasmic antibodies may be a risk factor for patient survival in scanty immune deposits lupus nephritis patients., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

The COVID-19 pandemic has severely affected healthcare worldwide and has led to the excessive use of disinfectants and antimicrobial agents. However, the impact of excessive disinfection measures and specific medication prescriptions on the development and dissemination of bacterial drug resistance during the pandemic remains unclear. This study investigated the influence of the pandemic on the composition of antibiotics, antibiotic resistance genes (ARGs), and pathogenic communities in hospital wastewater using ultra-performance liquid chromatography-tandem mass spectrometry and metagenome sequencing. The overall level of antibiotics decreased after the COVID-19 outbreak, whereas the abundance of various ARGs increased in hospital wastewater. After COVID-19 outbreak, bla OXA , sul2, tetX, and qnrS had higher concentrations in winter than in summer. Seasonal factors and the COVID-19 pandemic have affected the microbial structure in wastewater, especially of Klebsiella, Escherichia, Aeromonas, and Acinetobacter. Further analysis revealed the co-existence of qnrS, bla NDM , and bla KPC during the pandemic. Various ARGs significantly correlated with mobile genetic elements, implying their potential mobility. A network analysis revealed that many pathogenic bacteria (Klebsiella, Escherichia, and Vibrio) were correlated with ARGs, indicating the existence of multi-drug resistant pathogens. Although the calculated resistome risk score did not change significantly, our results suggest that the COVID-19 pandemic shifted the composition of residual antibiotics and ARGs in hospital wastewater and contributed to the dissemination of bacterial drug resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Liquid‒liquid phase separation (LLPS) is a phenomenon driven by weak interactions between biomolecules, such as proteins and nucleic acids, that leads to the formation of distinct liquid-like condensates. Through LLPS, membraneless condensates are formed, selectively concentrating specific proteins while excluding other molecules to maintain normal cellular functions. Emerging evidence shows that cancer-related mutations cause aberrant condensate assembly, resulting in disrupted signal transduction, impaired DNA repair, and abnormal chromatin organization and eventually contributing to tumorigenesis. The objective of this review is to summarize recent advancements in understanding the potential implications of LLPS in the contexts of cancer progression and therapeutic interventions. By interfering with LLPS, it may be possible to restore normal cellular processes and inhibit tumor progression. The underlying mechanisms and potential drug targets associated with LLPS in cancer are discussed, shedding light on promising opportunities for novel therapeutic interventions., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: There are factors that significantly increase the risk of postoperative pulmonary infections in patients with primary hepatic carcinoma (PHC). Previous reports have shown that over 10% of patients with PHC experience postoperative pulmonary infections. Thus, it is crucial to prioritize the prevention and treatment of postoperative pulmonary infections in patients with PHC., Aim: To identify the risk factors for postoperative pulmonary infection in patients with PHC and develop a prediction model to aid in postoperative management., Methods: We retrospectively collected data from 505 patients who underwent hepatobiliary surgery between January 2015 and February 2023 in the Department of Hepatobiliary and Pancreaticospleen Surgery. Radiomics data were selected for statistical analysis, and clinical pathological parameters and imaging data were included in the screening database as candidate predictive variables. We then developed a pulmonary infection prediction model using three different models: An artificial neural network model; a random forest model; and a generalized linear regression model. Finally, we evaluated the accuracy and robustness of the prediction model using the receiver operating characteristic curve and decision curve analyses., Results: Among the 505 patients, 86 developed a postoperative pulmonary infection, resulting in an incidence rate of 17.03%. Based on the gray-level co-occurrence matrix, we identified 14 categories of radiomic data for variable screening of pulmonary infection prediction models. Among these, energy, contrast, the sum of squares (SOS), the inverse difference (IND), mean sum (MES), sum variance (SUV), sum entropy (SUE), and entropy were independent risk factors for pulmonary infection after hepatectomy and were listed as candidate variables of machine learning prediction models. The random forest model algorithm, in combination with IND, SOS, MES, SUE, SUV, and entropy, demonstrated the highest prediction efficiency in both the training and internal verification sets, with areas under the curve of 0.823 and 0.801 and a 95% confidence interval of 0.766-0.880 and 0.744-0.858, respectively. The other two types of prediction models had prediction efficiencies between areas under the curve of 0.734 and 0.815 and 95% confidence intervals of 0.677-0.791 and 0.766-0.864, respectively., Conclusion: Postoperative pulmonary infection in patients undergoing hepatectomy may be related to risk factors such as IND, SOS, MES, SUE, SUV, energy, and entropy. The prediction model in this study based on diffusion-weighted images, especially the random forest model algorithm, can better predict and estimate the risk of pulmonary infection in patients undergoing hepatectomy, providing valuable guidance for postoperative management., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To analyze the motion characteristics of lumbar facet joints and to observe the effect of weight-bearing on lumbar facet joints in the sitting position., Methods: Ten normal subjects (5 males and 5 females) were recruited and scanned by CT, and their lumbar 3D models were reconstructed by software. The images of flexion and extension of lumbar facet joints in the sitting position were collected without weight-bearing and weight-bearing 10 kg, and the 2D model was constructed by software. The 2D-3D model was matched to restore the flexion and extension motion changes of the subjects' lumbar spine in the sitting position. Coordinates were established in the middle of the vertebral body and copied to the facet joints. Measure and record the lumbar facet joint movement distance through coordinate system. The relevant data of facet joints were collected., Results: In the L3/4 segment, after weight loading, the displacement of the left facet joint in the X axis became larger, while that in the Y axis and Z axis decreased. The displacement of the right facet joint in the X axis and Y axis increased, and the Z axis displacement decreased. The rotation angle of the bilateral facet joints also decreased. In the L4/5 segment, after loading, the displacements of the X, Y, and Z axis displacements of both sides increase, while the rotation angles of α and β increase, while the rotation angle of γ decreases. In the L5/S1 segment, the displacements of the X, Y, and Z axes on the left side decrease. The displacement of the X and Y axes on the right side decreases, while the displacement on the Z axis increases. The rotation angles of α and γ increase, and the rotation angle of the β axis decreases., Conclusion: When sitting, the flexion and extension distance and rotational displacement of lumbar facet joints are not affected by weight-bearing. In addition, there is asymmetry in the movement of the left and right facet joints, and weight bearing has no effect on the asymmetry of the motion., (© 2023. The Author(s).)

The use of indoor air purifier (IAP) has received growing attention as a mitigation strategy for reducing indoor air pollution, but the evidence on their cardiovascular benefits is unclear. This study aims to evaluate whether the use of IAP can reduce the adverse effects of indoor particulate matter (PM) on cardiovascular health among young healthy population. A randomized, double-blind, cross-over, IAP intervention of 38 college students was conducted. The participants were assigned into two groups to receive the true and sham IAPs for 36 h in random order. Systolic and diastolic blood pressure (SBP; DBP), blood oxygen saturation (SpO 2 ), heart rate variability (HRV) and indoor size-fractioned particulate matter (PM) were real-time monitored throughout the intervention. We found that IAP could reduce indoor PM by 41.7-50.5 %. Using IAP was significantly associated with a reduction of 2.96 mmHg (95 % CI: -5.71, -0.20) in SBP. Increased PM was significantly associated with increased SBP (e.g., 2.17 mmHg [0.53, 3.81], 1.73 mmHg [0.32, 3.14] and 1.51 mmHg [0.28, 2.75] for an IQR increment of PM 1 [16.7 μg/m 3 ], PM 2.5 [20.6 μg/m 3 ] and PM 10 [37.9 μg/m 3 ] at lag 0-2 h, respectively) and decreased SpO 2 (-0.44 % [-0.57, -0.29], -0.41 % [-0.53, -0.30] and - 0.40 % [-0.51, -0.30] for PM 1 , PM 2.5 and PM 10 at lag 0-1 h, respectively), which could last for about 2 h. Using IAPs could halve indoor PM levels, even in relatively low air pollution settings. The exposure-response relationships suggested that the benefits of IAPs on BP may only be observed when indoor PM exposure is reduced to a certain level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The occurrence of antibiotics in the feces of elderly individuals in Shenzhen, China, was investigated by monitoring 78 compounds to understand the adverse effects and its association with antibiotic residues in animal products collected from local markets. In total, 18 compounds belonging to 5 classes of antibiotics were identified in 74 of 140 fecal samples. Furthermore, 17.9% of the fecal samples contained at least two antibiotics, and 14.3% of the samples showed antibiotic concentrations higher than 100 μg/kg. Cephalothin exhibited the highest detection frequency (22.1%), followed by azithromycin (15.7%) and tilmicosin (12.9%). Oxytetracycline, norfloxacin, and azithromycin showed extremely high concentrations (> 1000 μg/kg). Eight antibiotics were detected in the animal products, with detection frequencies ranging from 4.8 to 40.0%. Five antibiotics exhibited similar detection frequencies and strong correlations between the human fecal and animal product samples. Health risk assessment based on hazard quotients showed that ciprofloxacin in animal products and human feces posed a medium and high risk, respectively. The hazard quotients of oxytetracycline, norfloxacin, and azithromycin in the feces were greater than 1, indicating a high health risk. These findings suggest that the elderly individuals were frequently exposed to antibiotics via the food chain and faced health risks posed by these antibiotics., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The evidence for chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence is well established. The hepatocyte epithelium carcinogenesis caused by HBV has been investigated and reviewed in depth. Nevertheless, recent findings from preclinical and observational studies suggested that chronic HBV infection is equally important in extrahepatic cancer occurrence and survival, specifically gastrointestinal system-derived cancers. Immune microenvironment changes (immune-suppressive cytokine infiltration), epigenetic modification (N6-methyladenosine), molecular signaling pathways (PI3K-Akt and Wnt), and serum biomarkers such as hepatitis B virus X (HBx) protein are potential underlying mechanisms in chronic HBV infection-induced extrahepatic cancers. This narrative review aimed to comprehensively summarize the most recent advances in evaluating the association between chronic HBV infection and extrahepatic cancer risk and explore the potential underlying molecular mechanisms in the carcinogenesis induction of extrahepatic cancers in chronic HBV conditions., Competing Interests: Author XX is employed by Shanghai ETERN Biopharma Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Min, Wei, Xia, Wei, Li, Jin, Liu, Hu and Peng.)

Introduction: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for chronic kidney failure. Here, we aimed to assess the characteristics and prognosis of LN patients with AKI., Methods: AKI and AKI severity stages in LN patients were defined by the Kidney Disease Improving Global Outcomes (KDIGO) classification. Long-term renal outcomes and patient mortality between different stages of AKI were compared by Cox regression analysis., Results: Of 1272 LN patients, 225 (17.69%) had AKI and 72 (5.66%) were AKI stage 3. Compared with the non-AKI group, the proportion of male patients was significantly higher in the AKI group (p = 0.002). In addition, there were markedly higher proportions of hematologic system damage, more severe renal manifestations, and higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores in the AKI group than in the non-AKI group. The active and chronic lesions in renal biopsy were significantly higher in LN patients with AKI than those without AKI. During a median follow-up of 53 months, Kaplan-Meier curve showed that LN patients with AKI stage 3 had significantly poorer long-term renal outcomes (p = 0.002) and patient survival (p &lt; 0.001) than those without AKI. Furthermore, AKI stage 3, but not stage 1 or 2 was significantly associated with adverse renal outcomes (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.01-6.28, p = 0.048) and all-cause mortality (HR = 2.80, 95% CI: 1.18-6.61, p = 0.019) in LN patients. In patients with AKI, increased baseline serum creatinine and severe glomerular sclerosis were independent risk factors for worse renal outcomes, while higher blood pressure, increased baseline serum creatinine, and anti-Sjogren's syndrome A positivity could indicate poor survival., Discussion: LN patients with AKI stage 3, but not stages 1 and 2, have poorer long-term renal outcomes and patient survival. Our study demonstrates the importance of early identification and management of AKI in LN patients., (© 2023 S. Karger AG, Basel.)

Introduction: IgA nephropathy (IgAN) with serum antineutrophil cytoplasmic autoantibody (ANCA) positivity is uncommon. This study analyzed the clinicopathologic features and prognosis of IgAN patients with serum ANCA positivity., Methods: 2,864 IgAN patients were tested for ANCA by the indirect immunofluorescence assay and chemiluminescence immunoassay. Patients with serum ANCA positivity (n = 85) were identified, and their clinical, pathological, and prognostic characteristics were analyzed. They were compared with ANCA-negative IgAN patients (n = 170) and ANCA-associated systemic vasculitis (AAV) with renal involvement patients (n = 85) selected randomly., Results: 2.97% (85/2,864) of IgAN were ANCA positive, and 4 patients were diagnosed as having crescentic IgAN with ANCA positivity. The clinicopathological characteristics of ANCA-positive IgAN patients were comparable to ANCA-negative IgAN patients, but they had higher antinuclear antibody (ANA)-positive rates, lower levels of renal interstitial inflammation, and fewer immune depositions than ANCA-negative IgAN patients. Compared with AAV patients, ANCA-positive IgAN patients were younger and had fewer extrarenal manifestations, milder renal damage, and more immune complex depositions. The renal outcomes were similar between IgAN patients with and without ANCA positivity. Multivariate Cox analysis revealed that in IgAN patients with ANCA positivity, male, ANA positivity, higher serum creatinine and proteinuria, and more severe renal tubular atrophy/interstitial fibrosis were risk factors for adverse renal outcomes., Conclusion: The clinical, pathological features and prognosis of ANCA-positive IgAN patients were similar to those of ANCA-negative IgAN patients except for higher ANA-positive rate, milder renal inflammation, and fewer immune depositions. ANA positivity was an independent risk factor for adverse renal outcomes in ANCA-positive IgAN patients., (© 2023 S. Karger AG, Basel.)

Introduction: The aim of this study was to evaluate the association of peripheral eosinophil (EOS) count with disease activity and kidney outcomes in lupus nephritis (LN) patients., Methods: A total of 453 hospitalized and biopsy-proven LN patients at our hospital from 2006 to 2013 were enrolled, of which 388 patients had repeated measurements of EOS. Relationships were explored between average EOS and disease activity at baseline, using the systemic lupus erythematosus disease activity (SLEDAI) and activity index (AI) on kidney biopsy. Follow-up data were available through December 2016. The primary outcome measure was a composite of doubling of serum creatinine and end-stage kidney disease after a median follow-up of 51 months., Results: The mean age of the enrolled 388 LN patients was 33.1 ± 10.8 years old, and 335 (86%) were female. The median average peripheral EOS count was 0.033 (0.015-0.057) ×109/L. Mean AI and SLEDAI score were 6.8 ± 2.5 and 14.9 ± 5.4, respectively. Logistic regression models showed that decreased average EOS was independently associated with higher AI (≥6) and higher SLEDAI (≥15) (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.90-0.97; and OR 0.96, 95% CI: 0.93-0.99, respectively). There was a parabolic relationship between average EOS and the primary outcome, with hazard ratio (HR) > 1 for both levels ≤0.033 and >0.16 × 109/L., Conclusion: Lower EOS count was independently associated with severe disease activity and kidney progression in LN., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objective: This study retrospectively compared the safety and efficacy of oral corticosteroid therapy (OCT) and corticosteroid pulse therapy (CPT) in the treatment of IgA nephropathy., Methods: One ninety-two patients were diagnosed with IgA nephropathy and had an estimated glomerular filtration rate > 15mL/min/1.73m 2 and 24-h urine protein level of 0.75-3.5g. Patients were divided into CPT and OCT groups according to the treatment protocol. The differences in the efficacy and safety between the two groups were assessed by logistic regression analysis and propensity score matching., Results: Significant differences at baseline, including 24-h urine protein level and eGFR, were observed between the two groups. Logistic regression analysis indicated that the remission rate increased significantly, while the incidences of total adverse events and infections decreased in CPT group compared with the OCT group after adjusting the potential confounding factors. Forty-seven pairs of subjects are matched by using propensity score matching with similar baseline data. The results indicate that the total remission rate and complete remission rate were significantly higher, while the incidences of total adverse events were lower ( p  = 0.008) in the CPT group than in the OCT group. The subgroup analysis showed that CPT group was more likely to achieve remission in patients with initial 24-h urine protein levels falling into the range of 2-3.5 g and Oxford Classification of S1 or C1/2 ( p  < 0.05)., Conclusion: Among patients with IgA nephropathy and 24-h urine protein levels of 0.75-3.5g, CPT may be more effective than OCT in reducing urinary protein levels and improving renal function with a lower incidence of adverse events.

Docynia delavayi (Franch.) Schneid is an evergreen tree with multiple benefits and high development and utilization value. The fruit is consumed as fresh and dry fruit, juices, and other products. However, it is unknown the chemical changes that occur upon fruit maturation. The metabolite content of unripe and ripe fruit was examined using UPLC-MS/MS technology based on a broadly targeted metabolome. We identified 477 metabolites, of which 130 differed between ripe and unripe fruit. These compounds are primarily involved in the biosynthesis of secondary metabolites, such as pantothenic acid, flavonoids, and amino acids. Moreover, in ripe fruit, there are 94 metabolites that are upregulated, particularly flavonoids and terpenoids. In comparison, compounds associated with sour flavors (amino acids, phenolic acids, organic acids) are down-regulated. Remarkably, these metabolites have a strong relationship with the medicinal properties of D. delavayi . This study provides a global perspective of the D. delavayi fruit metabolome and a comprehensive analysis of metabolomic variations during fruit development, thereby increasing the knowledge of the metabolic basis of important fruit quality traits in D. delavayi fruit., Competing Interests: The authors declare there are no competing interests., (©2022 Chen et al.)

Objective: End-stage kidney disease (ESKD) patients have a higher risk of antibiotic-associated encephalopathy (AAE) than other patients. We aimed to evaluate the prevalence, risk factors and outcomes of AAE in ESKD patients., Method: A retrospective study of ESKD patients treated with intravenous antibiotics in our hospital from Jan. 1, 2006, to Dec. 31, 2015 was performed. AAE was diagnosed by the modified Delphi method. Control individuals were randomly selected from the remaining patients who did not exhibit neurologic symptoms. Logistic regression analysis was used to identify risk factors for AAE as well as the association between AAE and outcome., Result: A total of 2104 patients were included in the study. The prevalence of AAE in our study was 4.4% (92/2104). The multivariate logistic regression analysis revealed that anuria (OR = 8.04, 95% CI: 4.13-15.65, p  < 0.001), history of central nervous system disorder (OR = 3.03, 95% CI: 1.21-7.56, p  = 0.018) and hypoalbuminemia (OR= 1.87, 95% CI: 1.01-3.47, p  = 0.046) were independent factors associated with AAE in ESKD patients. After adjustment for confounders, AAE was associated with composite outcomes of in-hospital mortality and treatment withdrawal (OR = 4.36, 95% CI: 2.09-9.10, p  < 0.001)., Conclusion: The prevalence of AAE was 4.4% in ESKD patients and varied among different antibiotics. Anuria, history of central nervous system disorder and hypoalbuminemia were associated with AAE in ESKD patients. AAE is associated with worse outcomes in ESKD patients.

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

The surface glycoprotein (S protein) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was used to develop coronavirus disease 2019 (COVID-19) vaccines. However, SARS-CoV-2, especially the S protein, has undergone rapid evolution and mutation, which has remained to be determined. Here, we analyzed and compared the early (12 237) and the current (more than 10 million) SARS-CoV-2 strains to identify the mutation features and geographical distribution of the S gene and S protein. Results showed that in the early strains, most of the loci were with relative low mutation frequency except S: 23403 (4486 strains), while in the current strains, there was a surge in the mutation strains and frequency, with S: 23403 constantly being the highest one, but tremendously increased to approximately 1050 times. Furthermore, D614 (S: 23403) was one of the most highly frequent mutations in the S protein of Omicron as of March 2022, and most of the mutant strains were still from the United States, and the United Kingdom. Further analysis demonstrated that in the receptor-binding domain, most of the loci with low mutation frequency in the early strains, while S: 22995 was nowadays the most prevalent loci with 3 122 491 strains in the current strains. Overall, we compare the mutation features of the S region in SARS-CoV-2 strains between the early and the current stains, providing insight into further studies in concert with emerging SARS-CoV-2 variants for COVID-19 vaccines., (© 2022 Wiley Periodicals LLC.)

Background: Postoperative pancreatic fistula (PF) is a serious life-threatening complication after pancreaticoduodenectomy (PD). Our research aimed to develop a machine learning (ML)-aided model for PF risk stratification., Aim: To develop an ML-aided model for PF risk stratification., Methods: We retrospectively collected 618 patients who underwent PD from two tertiary medical centers between January 2012 and August 2021. We used an ML algorithm to build predictive models, and subject prediction index, that is, decision curve analysis, area under operating characteristic curve (AUC) and clinical impact curve to assess the predictive efficiency of each model., Results: A total of 29 variables were used to build the ML predictive model. Among them, the best predictive model was random forest classifier (RFC), the AUC was [0.897, 95% confidence interval (CI): 0.370-1.424], while the AUC of the artificial neural network, eXtreme gradient boosting, support vector machine, and decision tree were between 0.726 (95%CI: 0.191-1.261) and 0.882 (95%CI: 0.321-1.443)., Conclusion: Fluctuating serological inflammatory markers and prognostic nutritional index can be used to predict postoperative PF., Competing Interests: Conflict-of-interest statement: All authors declare that there is no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Recognizing the kinematic characteristics of lumbar facet joints is important for the prevention and treatment of lumbar degenerative diseases. Previous studies have been conducted in either the supine or standing position, and there are no measurements regarding the kinematic characteristics of the lumbar facet joints while sitting. The aim of this study was to measure and analyze lumbar facet joint motion characteristics while sitting., Methods: Ten subjects (5 males and 5 females) performed the movements of flexion-extension, left bending-right bending, and left rotation-right rotation in a sitting position. Dual Fluoroscopic Image System and computed tomography technique were used to measure the displacement and rotation angle of the lumbar facet joints of the subjects for analysis. The movement characteristics of L3-S1 were measured., Results: When the subjects were in sitting position, the lumbar vertebra mainly changed in Z-axis and α, β angle when they performed flexion-extension activities. The displacement of the left facet joint was 4.65 ± 1.99 mm at L3-4, 1.89 ± 2.99 mm at L4-5, and 0.80 ± 2.27 mm at L5-S1 in the Z-axis, and the displacement of the right facet joint was 3.20 ± 2.61 mm at L3-4, 1.71 ± 3.00 mm at L4-5, and 0.31 ± 1.69 mm at L5-S1 in the Z-axis. The rotation in the α angle was 6.00 ± 4.49° at L3-4, 3.51 ± 5.24° at L4-5, and 0.97 ± 4.13° at L5-S1, which was significant different. The rotation in the β angle was 2.30 ± 2.94°at L3-4, 0.16 ± 2.06° at L4-5, and 0.35 ± 1.74°at L5-S1, which was significant different. When the lumbar spine performed the activity of left bending-right bending, there were changes in rotation mainly in the Z-axis and β angle. The displacement of left facet joint in the Z-axis was 1.34 ± 2.84 mm at L3-4, 2.11 ± 0.88 mm at L4-5, and 0.72 ± 0.81 mm at L5-S1; the rotation in the β angle was 5.66 ± 2.70°at L3-4, 7.89 ± 2.59° at L4-5, and 1.28 ± 2.07° at L5-S1; when the lumbar spine performed the activity of left rotation-right rotation, there were changes in the β angle. The rotation of β angle was 4.09 ± 2.86° at L3-4, 2.14 ± 3.38° at L4-5, and 0.63 ± 1.85° at L5-S1., Conclusion: The lumbar facet joint motion in sitting position is different in each mode of motion. The horizontal displacement and rotation are predominant during flexion and extension activities, while there are different rotation in bending and rotation. The study shows the coupled motion of the lumbar facet joints while sitting, providing a new perspective on the kinematics of the lumbar spine and the etiology of lumbar degenerative diseases., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Cupressaceae is a conifer family distributed around the world. Cupressus and Juniperus are the main genera of the Cupressaceae family and have important medicinal value. This leads to confusion between Cupressus and Juniperus due to similar morphologies. Here, the complete cp genomes of two Cupressus (C. duclouxiana and C. funebri) and four Juniperus (J. chinensis, J. gaussenii J. pingii and J. procumbens) were sequenced. The results revealed that the length of the cp genomes ranged from 126,996 bp to 129,959 bp, with 119 genes comprising 82 protein-coding genes, 33 transfer RNAs and 4 ribosomal RNAs. All chloroplast genomes of Cupressus and Juniperus lost whole IR regions, which is consistent with gymnosperm cp genome studies. In addition, the number of SSRs per species ranged from 54 to 73 and was dominated by mononucleotide repeats. In the six cp genomes of Cupressus and Juniperus, five highly divergent regions, including accD, accD-rpl2, ycf1, ycf2 and rrn23-rrn4.5, can be used as DNA barcodes of interspecific relationships and potential genetic markers. We compared the gene selection pressures (C. chengiana as reference species), and 6 genes underwent positive selection, the majority of which were related to photosynthesis. Phylogenetic results showed that the monophyly of Cupressus and Juniperus supported most bootstrap support. Cupressus funebris and J. chinensis were resolved to be early diverging species within Cupressus and Juniperus, and the two genera were sister groups to each other. This research revealed a new understanding of the structural pluralism and phylogenetic relationships of Cupressaceae cp genomes. These results will facilitate comprehension of the complexity and diversity of conifer cp genomes., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Color is the major ornamental feature of the Rhododendron genus, and it is related to the contents of flavonoid in petals. However, the regulatory mechanism of flavonoid biosynthesis in Rhododendron pulchrum remains unknown. The transcriptome and metabolome analysis of Rhododendron pulchrum with white, pink and purple color in this study aimed to reveal the mechanism of flavonoid biosynthesis and to provide insight for improving the petal color., Results: Flavonoids and flavonols are the major components of flavonoid metabolites in R.pulchrum, such as laricitrin, apigenin, tricin, luteolin, isoorientin, isoscutellarein, diosmetin and their glycosides derivatives. With transcriptome and metabolome analysis, we found CHS, FLS, F3'H, F3'5'H, DFR, ANS, GT, FNS, IFR and FAOMT genes showed significantly differential expression in cultivar 'Zihe'. FNS and IFR were discovered to be associated with coloration in R.pulchrum for the first time. The FNS gene existed in the form of FNSI. The IFR gene and its related metabolites of medicarpin derivatives were highly expressed in purple petal. In cultivar 'Fenhe', up-regulation of F3'H and F3'5'H and down-regulation of 4CL, DFR, ANS, and GT were associated with pink coloration. With the transcription factor analysis, a subfamily of DREBs was found to be specifically enriched in pink petals. This suggested that the DREB family play an important role in pink coloration. In cultivars 'Baihe', flavonoid biosynthesis was inhibited by low expression of CHS, while pigment accumulation was inhibited by low expression of F3'5'H, DFR, and GT, which led to a white coloration., Conclusions: By analyzing the transcriptome and metabolome of R.pulchrum, principal differential expression genes and metabolites of flavonoid biosynthesis pathway were identified. Many novel metabolites, genes, and transcription factors associated with coloration have been discovered. To reveal the mechanism of the coloration of different petals, a model of the flavonoid biosynthesis pathway of R.pulchrum was constructed. These results provide in depth information regarding the coloration of the petals and the flavonoid metabolism of R.pulcherum. The study of transcriptome and metabolome profiling gains insight for further genetic improvement in Rhododendron., (© 2022. The Author(s).)