Activin E-ACVR1C cross talk controls energy storage via suppression of adipose lipolysis in mice.

Body fat distribution is a heritable risk factor for cardiovascular and metabolic disease. In humans, rare Inhibin beta E (INHBE, activin E) loss-of-function variants are associated with a lower waist-to-hip ratio and protection from type 2 diabetes. Hepatic fatty acid sensing promotes INHBE expression during fasting and in obese individuals, yet it is unclear how the hepatokine activin E governs body shape and energy metabolism. Here, we uncover activin E as a regulator of adipose energy storage. By suppressing ß-agonist-induced lipolysis, activin E promotes fat accumulation and adipocyte hypertrophy and contributes to adipose dysfunction in mice. Mechanistically, we demonstrate that activin E elicits its effect on adipose tissue through ACVR1C, activating SMAD2/3 signaling and suppressing PPARG target genes. Conversely, loss of activin E or ACVR1C in mice increases fat utilization, lowers adiposity, and drives PPARG-regulated gene signatures indicative of healthy adipose function. Our studies identify activin E-ACVR1C as a metabolic rheostat promoting liver-adipose cross talk to restrain excessive fat breakdown and preserve fat mass during prolonged fasting, a mechanism that is maladaptive in obese individuals.

The role of insect intestinal microbes in controlling of Empoasca onukii Matsuda (Hemiptera: Cicadellidae) pest infestations in the production of tea garden: a review.

Pests like the phytophagous bug Empoasca onukii Matsuda frequently harm tea plants. The harm this insect does to agricultural and environmentally sensitive places is extremely harmful since physical and chemical prevention and control are still the primary methods of handling it. Therefore, it is important to develop pest management strategies. Recent research has demonstrated that pathogenic fungus and the gut microbiota interact to induce host and death, and that the gut microbiota, which has a dramatic effect on the host, can engage in pest control. The advancement of genome editing technologies is also new to the field of pest management. The diversity, function, and research methodologies of insect gut microbiota are summarized in this work, and discusses E. onukii Matsuda control options as well as the importance of insect gut microbiome in pest management. In comparison to traditional pesticides and physical prevention and control, the interaction between pathogenic fungi represented by Beauveria bassiana and intestinal microorganisms, as well as their participation in pest management, causes physiological stress on the host, which meets the new requirements of modern agricultural green development and has a protective effect on habitat fragmentation areas (Karst region). Exploring additional harmful fungus for pest management and fully using the specific traits of insect gut microbiota to achieve "killing insects with bacteria" would be a promising technique from this standpoint.

Comparison of porcine ALG and rabbit ATG on outcomes of HLA-haploidentical hematopoietic stem cell transplantation for patients with acquired aplastic anemia.

OBJECTIVE: To evaluate the efficacy and safety of P-ALG (porcine anti-lymphocyte globulin) and R-ATG (rabbit anti-thymocyte globulin) in the conditioning regime for patients with acquired aplastic anemia who underwent HLA-haploidentical hematopoietic stem cell transplantation (halpo-HSCT). METHODS: A total of 91 patients with acquired aplastic anemia who received haplo-HSCT at our center between January 2014 and December 2020 were retrospectively reviewed. Twenty-eight patients were in the P-ALG group while sixty-three patients were in the R-ATG group. RESULTS: The median time was 11 versus 13 days (P = 0.294) for myeloid engraftment and 12.5 versus 15 days (P = 0.465) for platelet engraftment in the P-ALG and R-ATG groups, respectively. There were no significant difference in 5-year overall survival (74.83% ± 8.24% vs 72.29% ± 6.26%, P = 0.830), GVHD-free, failure-free survival (71.05% ± 8.65% vs 62.71% ± 6.22%, P = 0.662), failure-free survival (74.83% ± 8.24% vs 66.09% ± 5.84%, P = 0.647) and transplantation-related mortality (25.17% ± 8.24% vs 26.29% ± 6.22%, P = 0.708) between the two groups. The incidence of aGVHD (acute graft versus host disease) (65.39% ± 9.33% vs 62.71% ± 6.30%, P = 0.653), II-IV aGVHD (38.46% ± 9.54% vs 35.64% ± 6.24%, P = 0.695), III-IV aGVHD (19.23% ± 7.73% vs 10.53% ± 4.07%, P = 0.291), cGVHD (chronic graft versus host disease) (22.22% ± 12.25% vs 22.31% ± 6.30%, P = 0.915), and moderate to severe cGVHD (5.56% ± 5.40% vs 9.28% ± 4.46%, P = 0.993) were not significantly different. Similar outcomes were observed between the P-ALG and R-ATG groups for severe bacterial infection (17.9% vs 25.4%, P = 0.431), invasive fungal diseases (3.6% vs 9.5%, P = 0.577) and graft rejection (0% vs 9.5%, P = 0.218). However, the incidence of cytomegalovirus infection and Epstein-Barr virus infection was significantly lower in the P-ALG group (46.4% vs 71.4%, P = 0.022; 3.6% vs 25.4%, P = 0.014). CONCLUSION: The efficacy and safety of P-ALG were similar with R-ATG in the setting of haplo-HSCT for patients with acquired aplastic anemia patients. P-ALG could be an alternative for R-ATG.

Assessing the contribution of tumor mutational phenotypes to cancer progression risk.

Cancer occurs via an accumulation of somatic genomic alterations in a process of clonal evolution. There has been intensive study of potential causal mutations driving cancer development and progression. However, much recent evidence suggests that tumor evolution is normally driven by a variety of mechanisms of somatic hypermutability, which act in different combinations or degrees in different cancers. These variations in mutability phenotypes are predictive of progression outcomes independent of the specific mutations they have produced to date. Here we explore the question of how and to what degree these differences in mutational phenotypes act in a cancer to predict its future progression. We develop a computational paradigm using evolutionary tree inference (tumor phylogeny) algorithms to derive features quantifying single-tumor mutational phenotypes, followed by a machine learning framework to identify key features predictive of progression. Analyses of breast invasive carcinoma and lung carcinoma demonstrate that a large fraction of the risk of future clinical outcomes of cancer progression-overall survival and disease-free survival-can be explained solely from mutational phenotype features derived from the phylogenetic analysis. We further show that mutational phenotypes have additional predictive power even after accounting for traditional clinical and driver gene-centric genomic predictors of progression. These results confirm the importance of mutational phenotypes in contributing to cancer progression risk and suggest strategies for enhancing the predictive power of conventional clinical data or driver-centric biomarkers.

The risk factors of neuropathic pain in neuromyelitis optica spectrum disorder: a retrospective case-cohort study.

BACKGROUND: Neuropathic pain is a common complication in neuromyelitis optica spectrum disorder (NMOSD), which seriously affects the quality of life of NMOSD patients, with no satisfactory treatment. And risk factors of neuropathic pain are still uncertain. OBJECTIVE: To investigate the risk factors of neuropathic pain in a NMOSD cohort. MATERIALS AND METHODS: Our study was a retrospective case-cohort study, the patients diagnosed with NMOSD in the Department of Neurology from the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2011 to October 2021 were screened. Inclusion criteria were: (1) patients diagnosed as NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria, (2) the aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) test was performed. Patients without AQP4-IgG antibody were excluded. Clinical data, including sex, age of the first onset, symptoms of the first episode including neuropathic pain and attack types, localization of lesions of the first episode on Magnetic Resonance Imaging (MRI), Extended disability status Scale (EDSS) of the first onset, treatment of immunosuppression in the first acute phase, disease modifying therapy (DMT), treatment of neuropathic pain and APQ4-IgG status were collected from the hospital system database. Neuropathic pain was defined according to the International Association for the Study of Pain criteria and was described as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system". RESULTS: One hundred nineteen patients were screened and finally 86 patients fulfilling the inclusion and exclusion criteria were enrolled in our study. The prevalence of neuropathic pain in patients with NMOSD was 43.0%. Univariate analysis showed that the factors associated with neuropathic pain were the age at the onset, the attack type of optic neuritis, the attack type of myelitis, length of spinal cord involvement, localization of thoracic lesion, optic lesion, upper thoracic lesions, lower thoracic lesions, extended spinal cord lesions (≥ 3 spinal lesions), extended thoracic lesions (≥ 4 thoracic lesions), intravenous immunoglobulin and mycophenolate mofetil. Multivariate regression analysis showed that extended thoracic lesions (OR 20.21 [1.18-346.05], P = 0.038) and age (OR 1.35 (1-1.81) P = 0.050) were independently associated with neuropathic pain among NMOSD patients and that gender (OR 12.11 (0.97-151.64) P = 0.053) might be associated with neuropathic pain among NMOSD patients. CONCLUSION: Extended thoracic lesions (≥ 4 thoracic lesions), age and gender might be independent risk factors of neuropathic pain among patients with NMOSD. However, with a small sample size and predominantly female, caution must be applied and these results need validating in further cohorts.

Clinical characteristics and risk factors of Aeromonas bloodstream infections in patients with hematological diseases.

BACKGROUND: To analyze the clinical features, risk factors and outcomes of Aeromonas bloodstream infections (BSIs) in patients with hematological diseases to establish an effective optimal therapy against it. METHODS: A retrospective study was performed by reviewing medical records of patients admitted to a tertiary blood disease hospital in China. Patients with hematological diseases who suffered from Aeromonas bacteremia during January 2002 to December 2020 were enrolled in this study. RESULTS: A total of 63 patients who developed Aeromonas bacteremia were enrolled in the study, and 91.9% of patients were neutropenic at the onset of BSIs. The major complications were skin and soft tissue infection (SSTI) (22.2%), followed by gastroenteritis (19.0%) and pneumonia (14.3%). High carbapenem resistance rates (70.8% for imipenem, 71.4% for meropenem) were note among the cases. Furthermore, Aeromonas strains isolated from five individuals developed resistance to quinolone, ß-lactams and tigecycline during the therapy. The 30-day mortality rate was 15.9%, while bacteremia with SSTI showed a much worse prognosis, with 50.0% (7/14) of the patients dying within 30 days of initiating the therapy. In the multivariate analysis, SSTI (OR = 28.72; 95% CI, 1.50-551.30; P = 0.026) and shock (OR = 47.58; 95% CI,1.06-2126.80; P = 0.046) were independent risk factors for mortality. CONCLUSIONS: Aeromonas bacteremia usually occurred in patients with neutropenic status, and patients with SSTIs were more likely to show a worse prognosis. Carbapenems should be avoided in patients with Aeromonas BSIs and SSTIs given high resistance rate.

High triglyceride is an independent predictor of high on-treatment platelet reactivity in ischemic stroke patients.

BACKGROUND: Previous studies have shown high triglyceride (TG) is associated with platelet hyperactivation in metabolic syndrome patients. However, limited information is available regarding this relationship on dual anti-platelet therapy (DAPT) in ischemic stroke (IS). In this study, we attempted to evaluate the association between TG and high on-treatment platelet reactivity (HTPR) in IS patients. METHODS: Ischemic stroke patients who received maintenance doses of clopidogrel and aspirin were categorized and analyzed retrospectively in this research. The platelet reactivity was assessed by Thromboelastography (TEG). If ADP-induced platelet inhibition rate (ADPi)<30%, it was defined as HTPR, else, it would be defined as normal on-treatment platelet reactivity (NTPR). Patients were divided into high-TG-level and lower-TG-level based on a TG level of 1.7mmol/L, the cutoff point of hypertriglyceridemia. A logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 123 patients were included in this study and 24 (19.51%) patients were identified as HTPR. HTPR was observed in 36.2% of the patients in high-TG-level (TG≥1.7mmol/L) group while only 9.2% of the patients in the low-TG-level group (TG<1.7mmol/L) were HTPR (P<0.001 ). According to multivariate analysis, TG≥1.7mmol/L was independently associated with HTPR (OR=14.715, 2.445-88.549,P=0.003). CONCLUSIONS: High TG is an independent predictor of HTPR in IS patients. For IS patients with high TG level undergoing DAPT, platelet reactivity should be monitored to identify HTPR, which may proactively help to optimize the anti-platelet therapy.

[Therapeutic effect of Shengjiang Powder on experimental autoimmune encephalomyelitis mice through IL-6/JAK2/STAT3 signaling pathway:based on HPLC].

A high performance liquid chromatography(HPLC) method was established to analyze the components in Shengjiang Powder(SJP) such as emodin and curcumin and explore its therapeutic effect on experimental autoimmune encephalomyelitis(EAE) mice. To be specific, HPLC was performed to determine the content of compounds in SJP such as emodin and curcumin. A total of 72 female SPF C57 BL/6 mice were randomized into control group(equivalent volume of ultrapure water, ig), model group(equivalent volume of ultrapure water, ig), low-, medium-, and high-dose SJP groups(SJP, ig), and positive control group(prednisone acetate, ig), 12 each group. EAE was induced in mice except the control group. Administration began from the first day after immunization. The general conditions, symptom score, and body weight of the mice were recorded. On the 21 st day, mouse brain tissues were separrated. Then hematoxylin-eosin(HE) staining and Luxol Fast Blue(LFB) staining were used to detect the pathological changes of brain tissues. Immunohistochemistry(IHC) was employed to determine the myelin basic protein(MBP) level, and Western blot the expression of occludin and claudin-5, as well as the levels of interleukin-6(IL-6) and proteins in the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) pathway and their phosphorylation levels. The mRNA expression of IL-6, JAK2, and STAT3 was detected by real-time quantitative polymerase chain reaction(qPCR). Finally, molecular docking of six main active components in SJP, including emodin and curcumin, with IL-6, JAK2 and STAT3 was performed, and the binding affinity was evaluated. The results showed that the established HPLC method demonstrated high precision, reproducibility, stability, and high recovery of samples. Compared with the model group, SJP reduced the clinical symptom score and alleviate the inflammatory infiltration of brain white matter and demyelination of EAE mice. At the same time, SJP increased the expression of occludin and claudin-5, down-regulated the mRNA expression of IL-6, JAK2, and STAT3, as well as the levels of IL-6/JAK/STAT3 proteins and the phosphorylation levels, with significant difference. Molecular docking suggested that the six active components in SJP had high binding energy with IL-6, JAK2, and STAT3 proteins. The established HPLC method is simple, accurate, and highly sensitive, which can simultaneously determine the content of emodin and curcumin in SJP. SJP may alleviate the clinical symptoms of EAE by inhibiting IL-6/JAK2/STAT3 signaling pathway, protecting the blood-brain barrier, and relieving the inflammatory response and demyelinization of brain tissue.

Systematic Evaluation of Fragmentation Methods for Unlabeled and Isobaric Mass Tag-Labeled O-Glycopeptides.

Dissecting site-specific functions of O-glycosylation requires simultaneous identification and quantification of differentially expressed O-glycopeptides by mass spectrometry. However, different dissociation methods have not been systematically compared in their performance in terms of identification, glycosite localization, and quantification with isobaric labeling. Here, we conducted this comparison on highly enriched unlabeled O-glycopeptides with higher-energy collision dissociation (HCD), electron-transfer/collision-induced dissociation (ETciD), and electron transfer/higher-energy collisional dissociation (EThcD), concluding that ETciD and EThcD with optimal supplemental activation resulted in superior identification of glycopeptides and unambiguous site localizations than HCD in a database search by Sequest HT. We later described a pseudo-EThcD strategy that in silico concatenates the electron transfer dissociation spectrum with the paired HCD spectrum acquired sequentially for the same precursor ions, which combines the identification advantage of ETciD/EThcD with the superior reporter ion quality of HCD. We demonstrated its improvements in identification and quantification of isobaric mass tag-labeled O-glycopeptides and showcased the discovery of the specific glycosites of GalNAc transferase 11 (GALNT11) in HepG2 cells.

Risk Factors and Outcomes of Antibiotic-resistant Pseudomonas aeruginosa Bloodstream Infection in Adult Patients With Acute Leukemia.

BACKGROUND: Pseudomonas aeruginosa (PA) bloodstream infection (BSI) is a common complication in patients with acute leukemia (AL), and the prevalence of antibiotic-resistant strains poses a serious problem. However, there is limited information regarding antibiotic resistance, clinical characteristics, and outcomes of PA BSI in AL patients. This study explored characteristics associated with the clinical outcomes of AL patients with PA BSI and analyzed factors associated with BSI caused by multidrug-resistant (MDR) or carbapenem-resistant strains. METHODS: This single-center retrospective study enrolled hospitalized AL patients who developed PA BSI during January 2014-December 2019. The Kaplan-Meier method was used to plot survival curves. Multivariate logistic regression analyses were also performed. RESULTS: Of 293 eligible patients with PA BSI, 55 (18.8%) received inappropriate empirical antibiotic therapy within 48 hours of BSI onset, whereas up to 65.8% MDR-PA BSI patients received inappropriate empirical treatment. The 30-day mortality rate was 8.5% for all patients. However, the 30-day mortality rates were 28.9% and 5.5% in MDR-PA BSI and non-MDR-PA BSI patients, respectively (P < .001). On multivariate analysis, previous use of quinolones (odds ratio [OR], 5.851 [95% confidence interval {CI}, 2.638-12.975]) and piperacillin/tazobactam (OR, 2.837 [95% CI, 1.151-6.994]) were independently associated with MDR-PA BSI; and MDR-PA BSI (OR, 7.196 [95% CI, 2.773-18.668]), perianal infection (OR, 4.079 [95% CI, 1.401-11.879]), pulmonary infection (OR, 3.028 [95% CI, 1.231-7.446]), and age ≥55 years (OR, 2.871 [95% CI, 1.057-7.799]) were independent risk factors for 30-day mortality. CONCLUSIONS: MDR increases mortality risk in PA BSI patients, and previous antibiotic exposure is important in MDR-PA BSI development. Rational antibiotic use based on local antimicrobial susceptibility and clinical characteristics can help reduce antibiotic resistance and mortality.

Autologous Hematopoietic Stem Cell Transplantation in Acute Myelogenous Leukemia.

The clinical outcomes of autologous hematopoietic stem cell transplantation (ASCT) in acute myelogenous leukemia (AML) have improved over time. Indeed, numerous studies have demonstrated that ASCT is associated with a lower relapse rate and acceptable nonrelapse mortality compared with chemotherapy alone in patients with AML. In addition, ASCT is also associated with comparable overall survival outcomes to those of allogeneic hematopoietic stem cell transplantation in some patients with AML. To date, age, cytogenetic and molecular risk stratification, and minimal residual disease (MRD) status have been shown to be closely related to clinical outcomes following ASCT. ASCT is recommended for patients with favorable-risk and intermediate-risk AML in first complete remission and patients with acute promyelocytic leukemia in second complete remission for whom a matched sibling donor is not available. MRD status pre-ASCT is the most important factor to consider when determining whether a patient is eligible for ASCT and can effectively predict clinical outcomes after ASCT. Advanced age is not an absolute contradiction for ASCT. In this review, we describe the literature and clinical trials evaluating the outcomes of ASCT in patients with AML and discuss the indications for ASCT therapy. Because the greatest concern in ASCT recipients is early relapse, important factors that should be monitored before ASCT and future perspectives in this area are also presented.

Associations of MDR1, TBXA2R, PLA2G7, and PEAR1 genetic polymorphisms with the platelet activity in Chinese ischemic stroke patients receiving aspirin therapy.

AIM: Aspirin resistance has an incidence of 5%-65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A2 receptor (TXA2 receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A2 (Lp-PLA2, encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine. In this study we examined the correlation between MDR1, TBXA2R, PLA2G7, PEAR1 genetic polymorphisms and platelet activity in Chinese ischemic stroke patients receiving aspirin therapy. METHODS: A total of 283 ischemic stroke patients receiving 100 mg aspirin for 7 d were genotyped for polymorphisms in MDR1 C3435T, TBXA2R (rs1131882), PLA2G7 (rs1051931, rs7756935), and PEAR1 (rs12566888, rs12041331). The platelet aggregation response was measured using an automatic platelet aggregation analyzer and a commercially available TXB2 ELISA kit. RESULTS: Thirty-three patients (11.66%) were insensitive to aspirin treatment. MDR1 3435TT genotype carriers, whose arachidonic acid (AA) or adenosine diphosphate (ADP)-induced platelet aggregation was lower than that of CC+CT genotype carriers, were less likely to suffer from aspirin resistance (odds ratio=0.421, 95% CI: 0.233-0.759). The TBXA2R rs1131882 CC genotype, which was found more frequently in the aspirin-insensitive group (81.8% vs 62.4%) than in the sensitive group, was identified as a risk factor for aspirin resistance (odds ratio=2.712, 95% CI: 1.080-6.810) with a higher level of AA-induced platelet aggregation. Due to the combined effects of PLA2G7 rs1051931 and rs7756935, carriers of the AA-CC haplotype had a higher level of ADP-induced platelet aggregation, and were at considerably higher risk of aspirin resistance than noncarriers (odds ratio=8.233, 95% CI: 1.590-42.638). CONCLUSION: A considerable portion (11.66%) of Chinese ischemic stroke patients are insensitive to aspirin treatment, which may be correlated with the MDR1 C3435T, TBXA2R (rs1131882), and PLA2G7 (rs1051931-rs7756935) polymorphisms.

Associations of CYP3A4, NR1I2, CYP2C19 and P2RY12 polymorphisms with clopidogrel resistance in Chinese patients with ischemic stroke.

AIM: There is a high incidence of the antiplatelet drug clopidogrel resistance (CR) in Asian populations. Because clopidogrel is a prodrug, polymorphisms of genes encoding the enzymes involved in its biotransformation may be the primary influential factors. The goal of this study was to investigate the associations of polymorphisms of CYP3A4, NR1I2, CYP2C19 and P2RY12 genes with CR in Chinese patients with ischemic stroke. METHODS: A total of 191 patients with ischemic stroke were enrolled. The patients were treated with clopidogrel for at least 5 days. Platelet function was measured by light transmission aggregometry. The SNPs NR1I2 (rs13059232), CYP3A4(*)1G (rs2242480), CYP2C19(*)2 (rs4244285) and P2RY12 (rs2046934) were genotyped. RESULTS: The CR rate in this population was 36%. The CYP2C19(*)2 variant was a risk factor for CR ((*)2/(*)2+wt/(*)2 vs wt/wt, OR: 2.366, 95% CI: 1.180-4.741, P=0.014), whereas the CYP3A4(*)1G variant had a protective effect on CR ((*)1/(*)1 vs (*)1G/(*)1G+(*)1/(*)1G, OR: 2.360, 95% CI: 1.247-4.468, P=0.008). The NR1I2 (rs13059232) polymorphism was moderately associated with CR (CC vs TT+TC, OR: 0.533, 95% CI: 0.286-0.991, P=0.046). The C allele in P2RY12 (rs2046934) was predicted to be a protective factor for CR (CC+TC vs TT, OR: 0.407, 95% CI: 0.191-0.867, P=0.018). In addition, an association was found between hypertension and CR (P=0.022). CONCLUSION: The individuals with both the CYP2C19(*)2 allele and hypertension are at high risk of CR during anti-thrombosis therapy. The CYP3A4(*)1G allele, P2RY12 (rs2046934) C allele and NR1I2 (rs13059232) CC genotype may be protective factors for CR. The associated SNPs studied may be useful to predict clopidogrel resistance in Chinese patients with ischemic stroke.

Climate change may drive the distribution of tribe Zyginelline pests in China and the Indo-China Peninsula to shift towards higher latitude river-mountain systems.

BACKGROUND: Tribe Zyginelline leafhoppers can transmit plant viruses and are important pests that affect agriculture, forestry, and animal husbandry, causing serious economic losses. The potential distribution patterns of Zyginellini will change under climate change. Therefore, the best-performing random forest and maximum entropy models among 12 commonly used ecological niche models, alongside an ensemble model, were selected to predict the changes in habitat suitability distribution of Zyginellini under current and future climate scenarios [represented by two shared socio-economic pathways (SSPs), namely SSP126 and SSP585, for three periods (2050s, 2070s, and 2090s)] in China and the Indo-China Peninsula for the first time. RESULTS: The results revealed that the distribution of Zyginellini was mainly dominated by minimum temperature of coldest month. Under current and future climate scenarios, Zyginellini was mostly distributed southeast of the 400 mm equivalent precipitation line in China, and Vietnam. Under the future SSP126 scenario, the alert areas will mainly be concentrated in Hunan, Jiangxi, Zhejiang, Anhui, and Hebei in China, alongside Myanmar and Thailand in the Indo-China Peninsula. Meanwhile, in the SSP585 scenario, the alert areas in China will increase, whereas there will be little change in the Indo-China Peninsula. Interestingly, from the current to the future, the cores of Zyginelline distribution occurred around rivers and mountains, and shifted from Guizhou along the Yuanjiang River system to higher latitudes in Hunan. CONCLUSION: Zyginellini prefers higher latitude river-mountain systems under climate change. Our results will contribute to effective pest control strategies and biogeographical research for Zyginellini alongside other Cicadellidae insects. © 2023 Society of Chemical Industry.

Genetic differentiation and phylogeography of Erythroneurini (Hemiptera, Cicadellidae, Typhlocybinae) in the southwestern karst area of China.

Erythroneurini is the largest tribe of the microleafhopper subfamily Typhlocybinae. Most prior research on this tribe has focused on traditional classification, phylogeny, and control of agricultural pests, and the phylogeography of the group remains poorly understood. In this study, the mitochondrial genomes of 10 erythroneurine species were sequenced, and sequences of four genes were obtained for 12 geographical populations of Seriana bacilla. The new sequence data were combined with previously available mitochondrial DNA sequence data and analyzed using Bayesian and Maximum-Likelihood-based phylogenetic methods to elucidate relationships among genera and species and estimate divergence times. Seriana was shown to be derived from within Empoascanara. Phylogeographic and population genetic analysis of the endemic Chinese species Seriana bacilla suggest that the species diverged about 54.85 Mya (95% HPD: 20.76-66.23 million years) in the Paleogene period and that population divergence occurred within the last 14 million years. Ancestral area reconstruction indicates that Seriana bacilla may have originated in the central region of Guizhou, and geographical barriers are the main factors affecting gene flow among populations. Ecological niche modeling using the MaxEnt model suggests that the distribution of the species was more restricted in the past but is likely to expand in the future years 2050 and 2070.

Recurrent CNTN1 antibody-positive nodopathy: a case report and literature review.

Background: Contactin-1 (CNTN1) antibody-positive nodopathy is rare and exhibits distinct clinical symptoms such as tremors and ataxia. However, the mechanisms of these symptoms and the characteristics of the cerebral spinal fluid (CSF) remain unknown. Case presentation: Here, we report a case of recurrent CNTN1 antibody-positive nodopathy. Initially, a 45-year-old woman experiencing numbness in the upper limbs and weakness in the lower limbs was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Eleven years later, her symptoms worsened, and she began to experience tremors and ataxia. Tests for serum CNTN1, GT1a, and GQ1b antibodies returned positive. Subsequently, she was diagnosed with CNTN1 antibody-positive nodopathy and underwent plasmapheresis therapy, although the treatment's efficacy was limited. To gain a deeper understanding of the disease, we conducted a comprehensive literature review, identifying 52 cases of CNTN1 antibody-positive nodopathy to date, with a tremor prevalence of 26.9%. Additionally, we found that the average CSF protein level in CNTN1 antibody-positive nodopathy was 2.57 g/L, with 87% of patients exhibiting a CSF protein level above 1.5 g/L. Conclusion: We present a rare case of recurrent CNTN1 antibody-positive nodopathy. Our findings indicate a high prevalence of tremor (26.9%) and elevated CSF protein levels among patients with CNTN1 antibody-positive nodopathy.

Risk factors of neuropathic pain in multiple sclerosis: a retrospective case-cohort study.

Background: Pain is a common symptom in multiple sclerosis (MS), especially neuropathic pain, which has a significant impact on patients' mental and physical health and quality of life. However, risk factors that related to neuropathic pain, still remain unclear. Objective: The study aimed to explore the risk factors of neuropathic pain among MS patients. Materials and methods: This retrospective study examined the consecutive patients diagnosed with MS in the Department of Neurology of Guangdong Provincial Hospital of Chinese Medicine between August 2011 and October 2022. Neuropathic pain was defined as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system". Demographic and clinical features were obtained from the electronic system of the hospital. Results: Our cohort revealed that the prevalence of patients with neuropathic pain in MS was 34.1%. The results indicated that the longer the spinal lesions, the greater the neuropathic pain risks (2-4: OR, 13.3(2.1-82), >5: OR, 15.2(2.7-86.8), p for tread: 0.037). Meanwhile, multivariate regression analysis showed that cervical and thoracic lesions (OR 4.276, 95% CI 1.366-13.382, P = 0.013), upper thoracic lesions (T1-T6) (OR 3.047, 95% CI 1.018-9.124, P = 0.046) were positively correlated with neuropathic pain, while basal ganglia lesions (OR 0.188, 95% CI 0.044-0.809, P = 0.025) were negatively correlated with neuropathic pain among MS patients. Conclusion: Extended spinal lesions (≥3 spinal lesions), cervical and thoracic lesions, upper thoracic lesions were independent risk factors of neuropathic pain among MS patients. Furthermore, our study found that the longer the spinal lesions, the greater the neuropathic pain risks.

Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.

The multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus.

Perturbed liver gene zonation in a mouse model of non-alcoholic steatohepatitis.

Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal hepatic function. Wnt signaling is a master regulator of spatial liver zonation. A perivenous-periportal Wnt activity gradient orchestrates metabolic zonation by activating gene expression in perivenous hepatocytes, while suppressing gene expression in their periportal counterparts. However, the understanding as to the liver gene zonation and zonation regulators in diseases is limited. Non-alcoholic steatohepatitis (NASH) is a chronic liver disease characterized by fat accumulation, inflammation, and fibrosis. Here, we investigated the perturbation of liver gene zonation in a mouse NASH model by combining spatial transcriptomics, bulk RNAseq and in situ hybridization. Wnt-target genes represented a major subset of genes showing altered spatial expression in the NASH liver. The altered Wnt-target gene expression levels and zonation spatial patterns were in line with the up regulation of Wnt regulators and the augmentation of Wnt signaling. Particularly, we found that the Wnt activator Rspo3 expression was restricted to the perivenous zone in control liver but expanded to the periportal zone in NASH liver. AAV8-mediated RSPO3 overexpression in controls resulted in zonation changes, and further amplified the disturbed zonation of Wnt-target genes in NASH, similarly Rspo3 knockdown in Rspo3+/- mice resulted in zonation changes of Wnt-target genes in both chow and HFD mouse. Interestingly, there were no impacts on steatosis, inflammation, or fibrosis NASH pathology from RSPO3 overexpression nor Rspo3 knockdown. In summary, our study demonstrated the alteration of Wnt signaling in a mouse NASH model, leading to perturbed liver zonation.

Effect of leukocytes on semen quality in men from primary and secondary infertile couples: A cross-sectional study.

Background and Aims: Leukocytospermia (LCS) is a known cause of male infertility. However, the relationship between seminal leukocytes and semen quality among infertile couples remains controversial. This study aims to investigate the association between semen quality and LCS in male partners of infertile couples. Methods: Semen samples were collected from 512 men who asked for a fertility evaluation in a reproductive center in China. Seminal leukocytes were counted following peroxidase staining with benzidine. Other semen parameters were compared in subfertile men with and without LCS. Results: Poor semen quality (e.g., low semen volume, sperm concentration, and sperm progressive/total motility) was observed among men with LCS compared to those without LCS. Men with LCS had a higher risk of low sperm progressive motility (OR = 0.99, 95% CI = 0.98-0.99, p = 0.02) and total motility (OR = 0.99, 95% CI = 0.98-0.99, p = 0.02), even after adjustment for potential confounders (both OR = 0.99, 95% CI = 0.98-0.99, p = 0.03). Lower sperm viability was observed in LCS from male partners of secondary couples, while no significant difference in semen parameters was found between men with and without LCS in male partners of primary infertile couples. Low sperm motility and viability were associated with LCS in men from secondary infertile couples after adjusting for confounders (OR = 0.97, 95% CI = 0.95-0.99, p = 0.04; OR = 0.94, 95% CI = 0.89-0.99, p = 0.04, respectively). Conclusions: Our findings indicate that a higher risk of abnormal semen parameters was correlated with an increased number of leukocytes in men from secondary infertile couples.