Di-(2-ethylhexyl) phthalate exposure induces premature testicular senescence by disrupting mitochondrial respiratory chain through STAT5B-mitoSTAT3 in Leydig cell.

Di-(2-ethylhexyl) phthalate (DEHP), a prevalent plasticizer, is known to have endocrine-disrupting effects on males and cause reproductive toxicity. There were causal effects of DEHP on testosterone levels in the real world by Mendelian randomization analysis. Exposure to DEHP during the preadult stage might lead to premature testicular senescence, but the mechanisms responsible for this have yet to be determined. In this study, we administered DEHP (300 mg/kg/day) to male C57BL/6 mice from postnatal days 21 to 49. The mice were kept for 6 months without DEHP. RNA sequencing was conducted on testicular tissue at PNM6. The results indicated that DEHP hindered testicular development, lowered serum testosterone levels in male mice, and induced premature testicular senescence. TM3 Leydig cells were exposed to 300 µM of mono(2-ethylhexyl) phthalate (MEHP), the bioactive metabolite of DEHP, for 72 h. The results also found that DEHP/MEHP induced senescence in vivo and in vitro. The mitochondrial respiratory chain was disrupted in Leydig cells. The expression and stability of STAT5B were elevated by MEHP treatment in TM3 cells. Furthermore, p-ERK1/2 was significantly decreased by STAT5B, and mitochondria-STAT3 (p-STAT3 ser727) was significantly decreased due to the decrease of p-ERK1/2. Additionally, the senescence level of TM3 cells was decreased and treated with 5 mM NAC for 1 h after MEHP treatment. In conclusion, these findings provided a novel mechanistic understanding of Leydig cells by disrupting the mitochondrial respiratory chain through STAT5B-mitoSTAT3.

Psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors.

PD-1 (programmed Death-1) immune checkpoint inhibitors have provided significant benefits to tumor patients. However, a considerable proportion of the patients develop immune-related adverse events (irAEs), of which cutaneous irAEs (cirAEs, e.g., psoriasis) occur relatively early. This review provides an overview of the current progress in psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. It not only describes the relevant influencing factors but also theoretically analyzes the immunological mechanisms that lead to the onset or exacerbation of psoriasis. Finally, the authors present guidelines for the treatment of psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. The review is intended to assist dermatologists in the early recognition and effective individualized management of such cirAE, which is helpful to continue or adjust the tumor-targeted immunotherapy on the basis of ensuring the quality of life of tumor patients.

Sivelestat in Patients at a High Risk of Postoperative Acute Lung Injury After Scheduled Cardiac Surgery: A Prospective Cohort Study.

Background: Sivelestat, a neutrophil elastase inhibitor, is specifically developed to mitigate the occurrence of acute lung injury (ALI) in individuals who are undergoing cardiovascular surgery. However, its impact on patients who are at a heightened risk of developing ALI after scheduled cardiac surgery has yet to be determined. In order to address this knowledge gap, we undertook a study to assess the efficacy of sivelestat in protecting the lungs of these patients. Methods: We conducted a prospective cohort study involving 718 patients who were at high risk of developing postoperative acute lung injury (ALI) and underwent scheduled cardiac surgery between April 25th, 2022, and September 7th, 2023. Among them, 52 patients received sivelestat (administered at a dosage of 0.2mg/kg/h for 3 days), while 666 patients served as controls, not receiving sivelestat. The control conditions were the same for all patients, including ventilation strategy, extubating time, and fluid management. Subsequently, a propensity-score matched cohort was established, consisting of 40 patients in both the sivelestat and control groups. The primary outcome measure encompassed a composite of adverse outcomes, including 30-day mortality, ALI, acute respiratory distress syndrome (ARDS), and others. Secondary outcomes assessed included pneumonia, ventricular arrhythmias, mechanical ventilation (MV) time, and more. Results: After conducting propensity matching in our study, we observed that there were no significant differences in 30-day mortality between the sivelestat and control groups (0% vs 2.5%, P=0.32). However, the use of sivelestat exhibited a significant reduction in the incidence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) compared to the control group (0% vs 55%, P<0.01), pneumonia (0 vs 37.5%, P<0.01), MV time (median:8 hours, IQR:4-14.8 hours vs median: 15.2 hours, IQR:14-16.3 hours, P<0.01). Compared to the control group, the sivelestat could significantly decrease white cell count (P<0.01), neutrophile percentage (P<0.01) and C-reactive protein (P<0.01) in the period of postoperative 5 days. Conclusion: The prophylactic administration of sivelestat has shown promising results in reducing the occurrence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with a heightened risk of developing these conditions after elective cardiac surgery. Our study findings indicate that sivelestat may provide protective effects by suppressing inflammation triggered by neutrophil activation, thereby safeguarding pulmonary function. Registration: ChiCTR2200059102, https://www.chictr.org.cn/showproj.html?proj=166643.

Chlorothalonil exposure compromised mouse oocyte in vitro maturation through inducing oxidative stress and activating MAPK pathway.

Chlorothalonil (CTL) is widely used in agricultural production and antifoulant additive globally due to its broad spectrum and non-systemic properties, resulting in its widespread existence in foods, soil and water. Extensive evidence demonstrated that exposure to CTL induced adverse effects on organisms and in particular its reproductive toxicity has been attracted public concern. However, the influences of CTL on oocyte maturation is mysterious so far. In this study, we documented the toxic effects of CTL on oocyte in vitro maturation and the related underlying mechanisms. Exposure to CTL caused continuous activation of spindle assembly checkpoints (SAC) which in turn compromised meiotic maturation in mouse oocyte, featured by the attenuation of polar body extrusion (PBE). Detection of cytoskeletal dynamics demonstrated that CTL exposure weakened the acetylation level of α-tubulin and impaired meiotic spindle apparatus, which was responsible for the aberrant state of SAC. Meanwhile, exposure to CTL damaged the function of mitochondria, inducing the decline of ATP content and the elevation of reactive oxygen species (ROS), which thereby induced early apoptosis and DNA damage in mouse oocytes. In addition, exposure to CTL caused the alteration of the level of histone H3 methylation, indicative of the harmful effects of CTL on epigenetic modifications in oocytes. Further, the CTL-induced oxidative stress activated mitogen-activated protein kinase (MAPK) pathway and injured the maturation of oocytes. In summary, exposure to CTL damaged mouse oocyte in vitro maturation via destroying spindle assembly, inducing oxidative stress and triggering MAPK pathway activation.

Upper limit of normal ALT levels in health and metabolic diseases: Pooled analysis of 423,355 individuals with bootstrap modelling.

INTRODUCTION: Given the global rise in obesity-related metabolic diseases, the upper limit of normal (ULN) alanine aminotransferase (ALT) in individuals with and without metabolic diseases may have changed. We performed a meta-analysis combined with bootstrap modelling to estimate the ALT ULN levels for individuals with and without metabolic diseases. METHODS AND RESULTS: Two separate searches of the PubMed, Embase and Cochrane databases were performed, one to identify healthy individuals which yielded 12 articles (349,367 individuals); another to include those with potential metabolic diseases but without known liver disease which yielded 35 articles (232,388 individuals). We estimated the mean ALT using a random-effects mixed model and the ULN level (95th-percentile value) via a bootstrap model with 10,000 resamples. In individuals without metabolic diseases and known liver disease, the ALT ULN levels were 32 U/L overall; 36 U/L in males and 28 U/L in females. In analyses that included individuals with metabolic diseases, the ALT ULN levels were 40 U/L among the overweight/obese (29 U/L if normal weight) and 36 U/L among those with type 2 diabetes mellitus (T2DM) (33 U/L if no T2DM). On meta-regression of study-level factors, body mass index (coefficient 1.49, 95% CI 0.11-2.86, p = 0.03), high-density lipoprotein (coefficient -0.47, 95% CI -0.85-(-0.08), p = 0.02) and triglycerides (coefficient 0.19, 95% CI 0.12-0.25, p < 0.0001) correlated with ALT. CONCLUSION: We provide expected ranges of ALT ULN levels for individuals without known liver disease without metabolic diseases and those with or without T2DM and/or are normal weight or overweight/obese. These data may have implications for clinical care and screening.

[The Clinical-Biological Features and Prognosis of Patients with Mantle Cell Lymphoma].

OBJECTIVE: To analyze the clinical-biological features and outcomes of patients with mantle cell lymphoma (MCL). METHODS: The clinical and laboratory data of 104 patients with newly diagnosed MCL who were admitted to the Department of Hematology, Fujian Medical University Union Hospital from January 2011 to December 2019 were retrospectively analyzed, and the efficacy was observed through survival analysis. RESULTS: Among 104 MCL patients, 88 were male and 16 were female. The median age was 54 (25-79) years old, 93.0% (93/100) of the patients with advanced stage (III and IV stages) and 48.08% (50/104) of the patients with bone marrow infiltration. Patients with Ki-67≥50% had higher WBC counts and LDH levels. Univariate analysis showed that the patients with WBC≥15×109/L, bone marrow involvement, high LDH, high ß2-MG levels, Ki-67≥50%, SOX11-, had lower OS and EFS rates (P =0.005, 0.049, 0.033, 0.025, 0.042, 0.018 and 0.001, 0.021, 0.024, 0.035, 0.014, 0.026). The OS rate and EFS rate of patients in R-CHOP and R-Hyper-CVAD treatment groups were significantly higher than those in other treatment groups (P =0.02, 0.002 and P =0.001, 0.001). Patients with autologous stem cell transplantation (ASCT) had higher OS rate and EFS rate (P =0.037, 0.013). Multivariate COX analysis showed that only WBC count, SOX11 expression and whether achieved CR after 4 courses treatment were the independent factors affecting the prognosis. CONCLUSION: MCL mainly occur in elderly men. There are many factors affecting patients' survival, while WBC≥15×109/L, negative expression of SOX11 and failure to achieve CR after 4 courses of treatment are adverse factors for MCL patients.

Carcinosarcoma of the deep lobe of the parotid gland in the parapharyngeal region: A case report.

BACKGROUND: Salivary carcinosarcoma is an extremely rare tumor containing both malignant epithelial and mesenchymal constituents. This article reports a rare case of carcinosarcoma with salivary duct carcinoma and osteosarcoma as the tumor components. The clinicopathological characteristics, treatment, and prognosis are discussed in conjunction with the literature. CASE SUMMARY: A 48-year-old man presented with a complaint of a mass in the right parotid region. Osteosarcoma was first considered for assessment by fine-needle aspiration cytology. Physical examination revealed a mass measuring approximately 4 cm × 3.5 cm × 3 cm. The mass, the whole lobe of the right parotid gland, and the right mandible were completely removed during surgery. Postoperative histopathology confirmed carcinosarcoma of the salivary gland. CONCLUSION: A definite diagnosis of salivary gland carcinosarcoma can only be obtained after complete surgical resection.

Impact of cognitive behavioral therapy on premature ejaculation patients: A prospective, randomized controlled trial protocol.

BACKGROUND: Premature ejaculation (PE) is one of the most common male sexual dysfunctions, with a prevalence of about 4%-39% in the Chinese population. Studies have shown that a variety of biological factors can lead to premature ejaculation, such as central nervous system disorders, hypersensitivity of the penis head, and psychological factors. Based on clinical experience, psychological counseling and education of patients and partners should be ranked as the first priority when treating PE. Cognitive behavioral therapy (CBT) addresses emotional, behavioral, and cognitive disorders by altering beliefs and actions. It has also been demonstrated to be clinically useful in treating a number of diseases. The purpose of this trial is to evaluate the efficacy of a mobile-based CBT intervention on patients with PE compared to conventional routine treatment. METHODS: This study is a prospective randomized controlled trial that will be conducted from May 2023 to Dec 2024 at ten hospitals, primarily including the First Affiliated Hospital of Sun Yat-sen University with an 8-week follow-up. The clinical trial central randomization system will be used to create and implement the specific randomization method. Baseline data of both groups will be measured and collected. The premature ejaculation diagnostic tool (PEDT) and the female sexual distress scale-revised for premature ejaculation (FSDS-R-PE) will be collected on the first day, 28±2 days, and 56±2 days during the intervention period, and the intravaginal ejaculatory latency time (IELT) will be measured in both groups. The Shapiro-Wilk test will be used for normality testing. Pearson correlation analysis will be used for correlation analysis. Differences between groups will be compared using analysis of variance or exact probability calculations. DISCUSSION: This study will investigate the effect of a mobile-based CBT intervention on patients with PE. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300070581).

Wittig/B─H insertion reaction: A unique access to trisubstituted Z-alkenes.

The Wittig reaction, which is one of the most effective methods for synthesizing alkenes from carbonyl compounds, generally gives thermodynamically stable E-alkenes, and synthesis of trisubstituted Z-alkenes from ketones presents notable challenges. Here, we report what we refer to as Wittig/B─H insertion reactions, which innovatively combine a Wittig reaction with carbene insertion into a B─H bond and constitute a promising method for the synthesis of thermodynamically unstable trisubstituted Z-boryl alkenes. Combined with the easy transformations of boryl group, this methodology provides efficient access to a variety of previously unavailable trisubstituted Z-alkenes and thus provides a platform for discovery of pharmaceuticals. The unique Z-selectivity of the reaction is determined by the maximum overlap of the orbitals between the B─H bond of the borane adduct and the alkylidene carbene intermediate in the transition state.

LncRNA RPLP0P2 Promotes Colorectal Cancer Proliferation and Invasion via the miR-129-5p/Zinc Finger and BTB Domain-Containing 20 Axis.

We previously reported that long non-coding RNA (lncRNA) RPLP0P2 is involved in the progression of colorectal cancer (CRC); however, its molecular mechanisms in CRC remain unclear. In this study, we observed that RPLP0P2 was upregulated in CRC tissues and cell lines. Cell viability was measured using the MTT and colony formation assays. Migration and invasion capabilities were monitored by wound healing, transwell, and immunofluorescence assays. The results showed that RPLP0P2 downregulation inhibited cell viability, migration, and invasion capabilities of CRC cells, accompanied by decreased PCNA, N-cadherin, and Vimentin, and increased E-cadherin expression. Using the DIANA online database, miR-129-5p was identified as a downstream target of RPLP0P2. In fact, RPLP0P2 colocalized with miR-129-5p, acting as a miR-129-5p sponge. MiR-129-5p-inhibition almost abrogated the anti-tumor effects induced by RPLP0P2 inhibition in CRC cells. Zinc finger and BTB domain-containing 20 (ZBTB20) was identified as a potential downstream target of miR-129-5p in CRC cells. ZBTB20 overexpression prevented miR-129-5p mimic-mediated anti-tumor effects in CRC cells. A tumor xenograft assay was performed to monitor the role of RPLP0P2 in tumor growth. Of note, in tumor-bearing mice, RPLP0P2-silencing inhibited tumor growth, followed by increased miR-129-5p and decreased ZBTB20 expression. Our results suggest that lncRNA RPLP0P2 functions as an oncogene that promotes CRC cell proliferation and invasion via regulating the miR-129-5p/ZBTB20 axis, thus, it may serve as a candidate target for CRC interventional therapies.

Seminal Plasma ExLncRNA Pairs: Updating Perspectives in the Search for Testicular Spermatozoa Retrieval Biomarkers in Nonobstructive Azoospermia Patients with mTESE by WGCNA.

PURPOSE: This study aims to find candidates for testicular spermatozoa retrieval biomarkers among the seminal plasma exLncRNA pairs. MATERIALS AND METHODS: A set of exLncRNA pairs with the best potential biomarkers was selected and validated in 96 NOA samples. Weighted correlation network analysis (WGCNA) and Least Absolute Shrinkage and Selection Operator were used to identify possible biomarkers for these pairs (LASSO). These pairs' potential biomarkers were identified using receiver operating curves. Confusion matrices and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), FP, false-negative rates (FNR), and F1 scores are calculated. Through F1 scores, we selected the best threshold value. RESULTS: The relative differential expression of each pair in testicular spermatozoa retrieval (+) and testicular spermatozoa retrieval (-) men were validated. The six pairs displayed the best biomarker potential. Among them, CCDC37.DT-LOCI00505685 pair and LOC440934- LOCI01929088 (XR_001745218.1) pair showed the most significant potential and stability for detecting testicular spermatozoa retrieval in the selected and validated cohort. CONCLUSION: CCDC37.DT-LOCI00505685 pair and LOC440934- LOCI01929088 (XR_001745218.1) pair have the potential to become new molecular biomarkers that could help to select clinical strategies for microdissection testicular sperm extraction.

TIM-3/Galectin-9 and CD160 expression in salivary adenoid cystic carcinoma.

OBJECTIVE: Investigating T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), Galectin 9 (Gal-9), CD160 expression and tumor-infiltrating lymphocytes (TILs) and correlation with clinicopathological characteristics of salivary adenoid cystic carcinoma (SACC). METHODS: Sixty cases of SACC were detected by immunohistochemical staining to evaluate TIM-3, Gal-9, and CD160 expression and analyze the correlation between TIM-3, Gal-9, CD160 expression and clinicopathologic features by rank-sum test. The association of TILs with TIM-3, Gal-9, and CD160 expression in SACC stromal was done by Chi-square test. RESULTS: TIM-3 and CD160 overexpression were correlated with recurrence of SACC (p = 0.029, p = 0.007, respectively). High Gal-9 expression was correlated with pathological classification (p = 0.018). The average percentage of TILs was 18.2% in SACC and most of TILs were more likely to occur in minor salivary glands (p = 0.038). Pairwise positive correlations were observed between the expression of TIM-3, Gal-9, and CD160 in tumor cells as well as in TILs, respectively. CONCLUSION: Low density of TILs was characteristic of the SACC microenvironment, with upregulation of TIM-3, Gal-9, and CD160 all occurring. However, TIM-3, Gal-9, and CD160 expression in the stromal dependent on the number of TILs represent potential therapeutic targets in SACC.

[Effects and mechanisms of total flavones of Abelmoschus manihot in improving insulin resistance and podocyte epithelial-mesenchymal transition in diabetic kidney disease based on IRS1/PI3K/Akt pathway].

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.

[Effects and mechanisms of total flavones of Abelmoschus manihot in attenuating diabetic tubulopathy by targeting endoplasmic reticulum stress-induced cell apoptosis].

Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.

Regulating and Predicting the Polyhedral Crystal Morphology in Spirofluorene Molecular Systems.

Crystallization of organic steric molecules often leads to multiple polyhedral crystal morphologies. However, the relationships among the molecular structure, supramolecular interaction, aggregation mode and crystal morphology are still unclear. In this work, we elaborate two model crystals formed by spiro[fluorene-9,9'-xanthene] (SFX) and spiro[cyclopenta[1,2-b : 5,4-b']dipyridine-5,9'-xanthene] (SDAFX) to demonstrate the feasibility of morphology prediction by periodic bond chain (PBC) theory based on interaction energy (IE) values in terms of single point energy. With non-directional van der Waals forces, only one PBC direction is found in SFX crystal, leading to the irregular 1D rod-like structure. Compared with SFX, the extra N heteroatoms in SDAFX can bring additional hydrogen bonds and some other interactions into the bulky molecular skeletons, inducing 3-dimensionally oriented PBCs to form the explicit F-face network in SDAFX which leads to the final octahedral structure. A simple and accurate method has been provided to quantify PBC vector on the supramolecular level in the organic molecular system, and the PBC theory has also been further demonstrated and developed in the morphology prediction of organic spiro-molecules.

[Analysis of Change and Driving Factors of River Environmental Quality in China from 2002 to 2020].

According to the river environmental quality, pollutant emission, and investment in environmental pollution control from 2002-2020, the change law and driving factors of river environmental quality in China were evaluated using canonical correlation analysis and the Spearman correlation coefficient to analyze the influence between environmental and pollutant emission/investment in environmental pollution control. The results indicated that the river environmental quality was improved significantly based on the proportion of Class Ⅰ-Ⅲ increasing from 29.1% to 87.4% and the proportion of inferior Class Ⅴ decreasing from 40.9% to 0.2% from 2002-2020. The emission of wastewater and domestic wastewater increased from 4.395×1010 tons and 2.323×1010 tons to 8.491×1010 tons and 6.598×1010 tons, respectively. However, emissions of industrial wastewater decreased from 2.072×1010 tons to 1.680×1010 tons. Investment in environmental pollution control increased from 110.66 billion yuan to 1063.89 billion yuan. The proportion of Class Ⅰ-Ⅲ in seven major river basins, river basins in Zhejiang and Fujian, southwest river basins, and northwest river basins showed a negative correlation for industrial pollutant emissions and a positive correlation for investment in environmental pollution control. The primary measure for the seven major river basins, river basins in Zhejiang and Fujian, and northwest river basins cut down the industrial pollutant emissions, in the order of COD>NH4+-N>total wastewater. The primary measure for southwest river basins increased the investment in environmental pollution control, in the order of industrial investment in environmental pollution control>urban environmental infrastructure construction investment and environmental protection investment in construction projects. These results can provide theoretical and policy suggestions for the improvement of river environmental quality during the "14th Five-Year Plan" period.

A cross-sectional study of the association between heavy metals and pan-cancers associated with sex hormones in NHANES 1999-2018.

Given the complexity of tumorigenesis, numerous studies have also shown that excessive exposure to heavy metals increases the risk of cancers and disrupts the secretion of sex hormones. However, the specific effects of heavy metals on cancers remain to be proven. To confirm the association between heavy metals and pan-cancer sex hormone levels among adults, 94,337 individuals from the National Health and Nutrition Examination Survey were assessed. We examined the associations between pan-cancers associated with sex hormones (ovarian, testicular, breast, and prostate cancers) and heavy metals in blood/urine. The methods (the WQS (weighted quantile sums) and SVYGLM (survey generalized linear model) regressions) were used to evaluate the association between sex hormone-related cancers and each metal category by incorporating covariates. To evaluate the overall effect of heavy metals and detect the dose-response relationship between the prevalence of pan-cancers associated with sex hormones and heavy metals, RCS (restricted cubic splines) were applied. Environmental exposure to heavy metals may be associated with pan-cancers associated with sex hormones in adults in the USA. Prostate cancer was inversely associated with blood cadmium while positively associated with blood lead, urinary tin, and thallium. Breast cancer was inversely associated with blood lead. Ovarian cancer was positively associated with blood cadmium. We also found a non-linear dose-response relationship between pan-cancers associated with sex hormones and heavy metals, which was non-parametric, using RCS models. The OR for breast cancer decreased along with the increase in lead concentration under approximately 20 µg/dl, while the OR for prostate cancer increased between urine thallium levels of approximately 0.17-1.1 ng/ml. Pan-cancers associated with sex hormones are associated with exposure to heavy metals. Considering the design of the NHANES study, further studies need to be conducted on other nationally representative surveys.

The Clinical-Biological Features and Prognosis of Patients with Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical-biological features and outcomes of patients with mantle cell lymphoma (MCL).@*METHODS@#The clinical and laboratory data of 104 patients with newly diagnosed MCL who were admitted to the Department of Hematology, Fujian Medical University Union Hospital from January 2011 to December 2019 were retrospectively analyzed, and the efficacy was observed through survival analysis.@*RESULTS@#Among 104 MCL patients, 88 were male and 16 were female. The median age was 54 (25-79) years old, 93.0% (93/100) of the patients with advanced stage (III and IV stages) and 48.08% (50/104) of the patients with bone marrow infiltration. Patients with Ki-67≥50% had higher WBC counts and LDH levels. Univariate analysis showed that the patients with WBC≥15×109/L, bone marrow involvement, high LDH, high β2-MG levels, Ki-67≥50%, SOX11-, had lower OS and EFS rates (P =0.005, 0.049, 0.033, 0.025, 0.042, 0.018 and 0.001, 0.021, 0.024, 0.035, 0.014, 0.026). The OS rate and EFS rate of patients in R-CHOP and R-Hyper-CVAD treatment groups were significantly higher than those in other treatment groups (P =0.02, 0.002 and P =0.001, 0.001). Patients with autologous stem cell transplantation (ASCT) had higher OS rate and EFS rate (P =0.037, 0.013). Multivariate COX analysis showed that only WBC count, SOX11 expression and whether achieved CR after 4 courses treatment were the independent factors affecting the prognosis.@*CONCLUSION@#MCL mainly occur in elderly men. There are many factors affecting patients' survival, while WBC≥15×109/L, negative expression of SOX11 and failure to achieve CR after 4 courses of treatment are adverse factors for MCL patients.

A Chromosome-level Reference Genome of African Oil Palm Provides Insights into Its Divergence and Stress Adaptation.

The palm family (Arecaceae), consisting of ∼ 2600 species, is the third most economically important family of plants. The African oil palm (Elaeis guineensis) is one of the most important palms. However, the genome sequences of palms that are currently available are still limited and fragmented. Here, we report a high-quality chromosome-level reference genome of an oil palm, Dura, assembled by integrating long reads with ∼ 150נgenome coverage. The assembled genome was 1.7 Gb in size, covering 94.5% of the estimated genome, of which 91.6% were assigned into 16 pseudochromosomes and 73.7% were repetitive sequences. Relying on the conserved synteny with oil palm, the existing draft genome sequences of both date palm and coconut were further assembled into chromosomal level. Transposon burst, particularly long terminal repeat retrotransposons, following the last whole-genome duplication, likely explains the genome size variation across palms. Sequence analysis of the VIRESCENS gene in palms suggests that DNA variations in this gene are related to fruit colors. Recent duplications of highly tandemly repeated pathogenesis-related proteins from the same tandem arrays play an important role in defense responses to Ganoderma. Whole-genome resequencing of both ancestral African and introduced oil palms in Southeast Asia reveals that genes under putative selection are notably associated with stress responses, suggesting adaptation to stresses in the new habitat. The genomic resources and insights gained in this study could be exploited for accelerating genetic improvement and understanding the evolution of palms.