Role of Pmk1, Mpk1, or Hog1 in the mitogen-activated protein kinase pathway of Aspergillus cristatus.

Aspergillus cristatus is a probiotic fungus known for its safety and abundant secondary metabolites, making it a promising candidate for various applications. However, limited progress has been made in researching A. cristatus due to challenges in genetic manipulation. The mitogen-activated protein kinase (MAPK) signaling pathway is involved in numerous physiological processes, but its specific role in A. cristatus remains unclear. In this study, we successfully developed an efficient polyethylene glycol (PEG)-mediated protoplast transformation method for A. cristatus, enabling us to investigate the function of Pmk1, Mpk1, and Hog1 in the MAPK signaling pathway. Our findings revealed that Pmk1, Mpk1, and Hog1 are crucial for sexual reproduction, melanin synthesis, and response to external stress in A. cristatus. Notably, the deletion of Pmk1, Mpk1, or Hog1 resulted in the loss of sexual reproduction capability in A. cristatus. Overall, this research on MAPK will contribute to the continued understanding of the reproductive strategy and melanin synthesis mechanism of A. cristatus.

A diabatization method based upon integrating the diabatic potential gradient difference.

In this work we develop a new scheme to construct a diabatic potential energy matrix (DPEM). We propose a diabatization method which is based on integrating the diabatic potential gradient difference to diabatize adiabatic ab initio energies. This method is capable of performing high-precision adiabatic-to-diabatic transformations, with a unique advantage in effectively handling the significant fluctuations in derivative-couplings caused by conical intersection (CI) seams. The above scheme is applied to the DPEM construction of the Na(3p) + H2 → NaH + H reaction. The fitting data including adiabatic energies, energy gradients and derivative-couplings obtained from a previous benchmark DPEM are diabatized and fitted using a general neural network fitting procedure to generate the DPEM. The produced DPEM can effectively describe nonadiabatic processes involving different electronic states. We further perform quantum dynamical calculations on the new DPEM and the previous benchmark DPEM, and the obtained results demonstrate the effectiveness of our scheme.

Association of serum sclerostin levels with marrow adiposity in postmenopausal women with glucocorticoid-induced osteoporosis.

BACKGROUND: Glucocorticoids and sclerostin act as inhibitors of the Wnt signaling pathway, thereby hindering bone formation. Given the pathway's intricate association with mesenchymal stem cells, the hypothesis suggests that heightened sclerostin levels may be intricately linked to an augmentation in marrow adiposity induced by glucocorticoids. This study endeavored to delve into the nuanced relationship between circulating sclerostin and bone marrow adipose tissue in postmenopausal women grappling with glucocorticoid-induced osteoporosis (GIO). METHODS: In this cross-sectional study, 103 patients with autoimmune-associated diseases underwent glucocorticoid treatment, boasting an average age of 61.3 years (standard deviation 7.1 years). The investigation encompassed a thorough assessment, incorporating medical history, anthropometric data, biochemical analysis, and dual-energy X-ray absorptiometry measurements of lumbar and femoral bone mineral density (BMD). Osteoporosis criteria were established at a T-score of -2.5 or lower. Additionally, MR spectroscopy quantified the vertebral marrow fat fraction. RESULTS: BMD at the femoral neck, total hip, and lumbar spine showcased an inverse correlation with marrow fat fraction (r = -0.511 to - 0.647, P < 0.001). Serum sclerostin levels exhibited a positive correlation with BMD at various skeletal sites (r = 0.476 to 0.589, P < 0.001). A noteworthy correlation emerged between circulating sclerostin and marrow fat fraction at the lumbar spine (r = -0.731, 95% CI, -0.810 to -0.627, P < 0.001). Multivariate analysis brought to light that vertebral marrow fat fraction significantly contributed to sclerostin serum concentrations (standardized regression coefficient ß = 0.462, P < 0.001). Even after adjusting for age, body mass index, physical activity, renal function, BMD, and the duration and doses of glucocorticoid treatment, serum sclerostin levels maintained a significant correlation with marrow fat fraction. CONCLUSIONS: Circulating sclerostin levels exhibited a noteworthy association with marrow adiposity in postmenopausal women grappling with GIO.

A novel transcriptional activation mechanism of inulinase gene in Kluyveromyces marxianus involving a glycolysis regulator KmGcr1p with unique and functional Q-rich repeats.

Kluyveromyces marxianus is the most suitable fungus for inulinase industrial production. However, the underlying transcriptional activation mechanism of the inulinase gene (INU1) is hitherto unclear. Here, we undertook genetic and biochemical analyses to elucidate that a glycolysis regulator KmGcr1p with unique Q-rich repeats is the key transcriptional activator of INU1. We determined that INU1 and glycolytic genes share similar transcriptional activation patterns and that inulinase activity is induced by fermentable carbon sources including the hydrolysis products of inulin (fructose and glucose), which suggests a novel model of product feedback activation. Furthermore, all four CT-boxes in the INU1 promoter are important for KmGcr1p DNA-binding in vitro, but the most downstream CT-box 1 primarily confers upstream activating sequence activity in vivo. More intriguingly, the use of artificial and natural GCR1 mutants suggests that the Q-rich repeats act as a functional module to maintain KmGcr1p transcriptional activity by contributing to its solubility and DNA-binding affinity. Altogether, this study uncovers a novel transcriptional activation mechanism for the inulinase gene, that is different from the previous understanding for filamentous fungi, but might have universal significance among inulinase-producing yeasts, thereby leading to a better understanding of the regulation mechanism of yeast inulinase genes.

Identification of MADS-Box Transcription Factors in Iris laevigata and Functional Assessment of IlSEP3 and IlSVP during Flowering.

Iris laevigata is ideal for gardening and landscaping in northeast China because of its beautiful flowers and strong cold resistance. However, the short length of flowering time (2 days for individual flowers) greatly limits its applications. Molecular breeding and engineering hold high potential for producing I. laevigata of desirable flowering properties. A prerequisite is to identify and characterize key flowering control genes, the identity of which remains largely unknown in I. laevigata due to the lack of genome information. To fill this knowledge gap, we used sequencing data of the I. laevigata transcriptome to identify MADS-box gene-encoding transcription factors that have been shown to play key roles in developmental processes, including flowering. Our data revealed 41 putative MADS-box genes, which consisted of 8 type I (5 Mα and 3 Mß, respectively) and 33 type II members (2 MIKC* and 31 MIKCC, respectively). We then selected IlSEP3 and IlSVP for functional studies and found that both are localized to the nucleus and that they interact physically in vitro. Ectopic expression of IlSEP3 in Arabidopsis resulted in early flowering (32 days) compared to that of control plants (36 days), which could be mediated by modulating the expression of FT, SOC1, AP1, SVP, SPL3, VRN1, and GA20OX. By contrast, plants overexpressing IlSVP were phenotypically similar to that of wild type. Our functional validation of IlSEP3 was consistent with the notion that SEP3 promotes flowering in multiple plant species and indicated that IlSEP3 regulates flowering in I. laevigata. Taken together, this work provided a systematic identification of MADS-box genes in I. laevigata and demonstrated that the flowering time of I. laevigata can be genetically controlled by altering the expression of key MADS-box genes.

Identification of glomerular lesions and intrinsic glomerular cell types in kidney diseases via deep learning.

Identification of glomerular lesions and structures is a key point for pathological diagnosis, treatment instructions, and prognosis evaluation in kidney diseases. These time-consuming tasks require a more accurate and reproducible quantitative analysis method. We established derivation and validation cohorts composed of 400 Chinese patients with immunoglobulin A nephropathy (IgAN) retrospectively. Deep convolutional neural networks and biomedical image processing algorithms were implemented to locate glomeruli, identify glomerular lesions (global and segmental glomerular sclerosis, crescent, and none of the above), identify and quantify different intrinsic glomerular cells, and assess a network-based mesangial hypercellularity score in periodic acid-Schiff (PAS)-stained slides. Our framework achieved 93.1% average precision and 94.9% average recall for location of glomeruli, and a total Cohen's kappa of 0.912 [95% confidence interval (CI), 0.892-0.932] for glomerular lesion classification. The evaluation of global, segmental glomerular sclerosis, and crescents achieved Cohen's kappa values of 1.0, 0.776, 0.861, and 95% CI of (1.0, 1.0), (0.727, 0.825), (0.824, 0.898), respectively. The well-designed neural network can identify three kinds of intrinsic glomerular cells with 92.2% accuracy, surpassing the about 5-11% average accuracy of junior pathologists. Statistical interpretation shows that there was a significant difference (P value < 0.0001) between this analytic renal pathology system (ARPS) and four junior pathologists for identifying mesangial and endothelial cells, while that for podocytes was similar, with P value = 0.0602. In addition, this study indicated that the ratio of mesangial cells, endothelial cells, and podocytes within glomeruli from IgAN was 0.41:0.36:0.23, and the performance of mesangial score assessment reached a Cohen's kappa of 0.42 and 95% CI (0.18, 0.69). The proposed computer-aided diagnosis system has feasibility for quantitative analysis and auxiliary recognition of glomerular pathological features. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Efficient simultaneous production of extracellular polyol esters of fatty acids and intracellular lipids from inulin by a deep-sea yeast Rhodotorula paludigena P4R5.

BACKGROUND: Polyol esters of fatty acids (PEFA) are a kind of promising biosurfactants and mainly secreted by Rhodotorula strains. In addition, some strains of Rhodotorula are reliable producers of microbial lipid. Therefore, it is feasible to establish a one step fermentation process for efficient simultaneous production of PEFA and microbial lipids by a suitable Rhodotorula strain. RESULTS: A newly isolated deep-sea yeast, Rhodotorula paludigena P4R5, was shown to simultaneously produce high level of intracellular lipid and extracellular PEFA. Under the optimized conditions, it could yield 48.5 g/L of PEFA and 16.9 g/L of intracellular lipid within 156 h from inulin during 10-L batch fermentation. The PEFA consisting of a mixture of mannitol esters of 3-hydroxy C14, C16 and C18 fatty acids with variable acetylation showed outstanding surface activity and emulsifying activity, while the fatty acids of the intracellular lipid were mainly C16 and C18 and could be high-quality feedstock for biodiesel production. CONCLUSION: The deep-sea yeast strain R. paludigena P4R5 was an excellent candidate for efficient simultaneous of biosurfactants and biodiesel from inulin. Our results also suggested that the establishment of fermentation systems with multiple metabolites production was an effective approach to improve the profitability.

Production of D -tagatose, bioethanol, and microbial protein from the dairy industry by-product whey powder using an integrated bioprocess.

We designed and constructed a green and sustainable bioprocess to efficiently coproduce D -tagatose, bioethanol, and microbial protein from whey powder. First, a one-pot biosynthesis process involving lactose hydrolysis and D -galactose redox reactions for D -tagatose production was established in vitro via a three-enzyme cascade. Second, a nicotinamide adenine dinucleotide phosphate-dependent galactitol dehydrogenase mutant, D36A/I37R, based on the nicotinamide adenine dinucleotide-dependent polyol dehydrogenase from Paracoccus denitrificans was created through rational design and screening. Moreover, an NADPH recycling module was created in the oxidoreductive pathway, and the tagatose yield increased by 3.35-fold compared with that achieved through the pathway without the cofactor cycle. The reaction process was accelerated using an enzyme assembly with a glycine-serine linker, and the tagatose production rate was 9.28-fold higher than the initial yield. Finally, Saccharomyces cerevisiae was introduced into the reaction solution, and 266.5 g of D -tagatose, 162.6 g of bioethanol, and 215.4 g of dry yeast (including 38% protein) were obtained from 1 kg of whey powder (including 810 g lactose). This study provides a promising sustainable process for functional food (D -tagatose) production. Moreover, this process fully utilized whey powder, demonstrating good atom economy.

New records of Harpiolaisodon (Chiroptera, Vespertilionidae) from the Chinese mainland.

Background: The new species, Harpiolaisodon Kuo et al., 2006, was described from Taiwan, China. So far, no distribution of this species outside Taiwan has been reported. New information: During two field investigations of small mammals in Guanyin Mountains Provincial Nature Reserve, Yuanyang, Yunnan, China, in April 2022 and May 2023, five individuals of Harpiola were collected in the mid-montane evergreen broad-leaved forest. Our morphological and molecular results reveal that these individuals from the Chinese mainland belong to Harpiolaisodon, extending the occurrence of this species well beyond its known distributions in Taiwan, China and Vietnam.

Identification and Genomic Characterization of Two Novel Hepatoviruses in Shrews from Yunnan Province, China.

Hepatitis A virus (HAV), a member of the genus Hepatovirus (Picornaviridae HepV), remains a significant viral pathogen, frequently causing enterically transmitted hepatitis worldwide. In this study, we conducted an epidemiological survey of HepVs carried by small terrestrial mammals in the wild in Yunnan Province, China. Utilizing HepV-specific broad-spectrum RT-PCR, next-generation sequencing (NGS), and QNome nanopore sequencing (QNS) techniques, we identified and characterized two novel HepVs provisionally named EpMa-HAV and EpLe-HAV, discovered in the long-tailed mountain shrew (Episoriculus macrurus) and long-tailed brown-toothed shrew (Episoriculus leucops), respectively. Our sequence and phylogenetic analyses of EpMa-HAV and EpLe-HAV indicated that they belong to the species Hepatovirus I (HepV-I) clade II, also known as the Chinese shrew HepV clade. Notably, the codon usage bias pattern of novel shrew HepVs is consistent with that of previously identified Chinese shrew HepV. Furthermore, our structural analysis demonstrated that shrew HepVs differ from other mammalian HepVs in RNA secondary structure and exhibit variances in key protein sites. Overall, the discovery of two novel HepVs in shrews expands the host range of HepV and underscores the existence of genetically diverse animal homologs of human HAV within the genus HepV.

Regression-based Chinese norms of number connection test A and digit symbol test for diagnosing minimal hepatic encephalopathy.

Number connection test A (NCT-A) and digit symbol test (DST), the preferential neuropsychological tests to detect minimal hepatic encephalopathy (MHE) in China, haven't been standardized in Chinese population. We aimed to establish the norms based on a multi-center cross-sectional study and to detect MHE in cirrhotic patients. NCT-A and DST were administered to 648 healthy controls and 1665 cirrhotic patients. The regression-based procedure was applied to develop demographically adjusted norms for NCT-A and DST based on healthy controls. Age, gender, education, and age by education interaction were all predictors of DST, while age, gender, and education by gender interaction were predictors of log10 NCT-A. The predictive equations for expected scores of NCT-A and DST were established, and Z-scores were calculated. The norm for NCT-A was set as Z ≤ 1.64, while the norm for DST was set as Z ≥ - 1.64. Cirrhotic patients with concurrent abnormal NCT-A and DST results were diagnosed with MHE. The prevalence of MHE was 8.89% in cirrhotic patients, and only worse Child-Pugh classification (P = 0.002, OR = 2.389) was demonstrated to be the risk factor for MHE. The regression-based normative data of NCT-A and DST have been developed to detect MHE in China. A significant proportion of Chinese cirrhotic patients suffered from MHE, especially those with worse Child-Pugh classification.

[An epidemiological study of food intolerance in 2434 children].

OBJECTIVE: To investigate the epidemiological characteristics of intolerance to 14 foods in children and the relationship between food intolerance and disease of various systems. METHODS: Serum samples of 2434 children with diseases were collected for food intolerance testing between January 2009 and October 2012. Allergen-specific IgG antibodies to 14 foods were detected using enzyme-linked immunosorbent assay. The children's intolerance to different foods and its relationship with age, sex and disease of various systems were analyzed. RESULTS: Among these children, positive rates of intolerance to milk and eggs were as high as 74.16% and 66.47% respectively, while positive rates of intolerance to chicken and pork were relatively low (0.29% and 0.21% respectively). The overall positive rates of food intolerance were 12.579% and 12.470% in males and females respectively. For infants, the highest intolerance rate was to milk; for preschool and school-age children, the highest intolerance rates were to milk and eggs respectively; for children in adolescence, the highest intolerance rate was to eggs. Among children with food intolerance involving single system, those with developmental abnormality or immune system disease had the highest overall positive rate of food intolerance. Children with double-system diseases had an overall positive rate of food intolerance as high as 13.393%. Among the children involving various systems, the positive rate of intolerance to milk and eggs were higher than other food. CONCLUSIONS: Factors influencing food intolerance in children include food categories and age. There may be a relationship between food intolerance and disease of various systems, and this is significant to the growth and development of children.

Greenness and chronic respiratory health issues: a systematic review and meta-analysis.

Introduction: The number of chronic respiratory disease (CRD) individuals worldwide has been continuously increasing. Numerous studies have shown that greenness can improve chronic respiratory health issues through different mechanisms, with inconsistent evidence. By quantitatively summarizing existing studies, our purpose is to determine the connection between greenness exposure and various chronic respiratory health. Methods: We conducted a comprehensive search on PubMed, EMBASE, and Web of Science core databases to identify relevant studies on the correlation between greenness exposure and chronic respiratory health issues. Studies published up to January 2023 were included in the search. The study used the most frequent indicator (normalized difference vegetation index [NDVI]) as the definition of greenness exposure. Results: We finally identified 35 studies for meta-analysis. We calculated pooled effects across studies using a random-effects model and conducted a subgroup analysis by age and buffer zones to discuss the effects on chronic respiratory health issues. This study showed that 0.1 increments in NDVI were significantly related to lower rates of asthma incidence, lung cancer incidence, and chronic obstructive pulmonary disease (COPD) mortality risk; the pooled RRs were 0.92 (95% CI: 0.85-0.98), 0.62 (95% CI: 0.40-0.95), and 0.95 (95% CI: 0.92- 0.99), respectively. For the age subgroup, the higher greenness exposure level was related to the incidence rate of asthma among teenagers aged 13-18years (RR: 0.91; 95% CI: 0.83-0.99). For the buffer subgroup, a positive relationship with greenness exposure and asthma incidence/prevalence at 200-300m and 800- 1000m buffers, as well as the COPD mortality at 800-1000m buffer, the pooled RRs were 0.92 (95% CI: 0.86-0.98), 0.87 (95% CI: 0.81-0.93), and 0.93 (95% CI: 0.88- 0.98), respectively. Evidence of publication bias was not detected in this study. Discussion: Our study is the first global meta-analysis between greenness and various CRDs to report an inverse association. Further research is needed in order to determine the effect of greenness exposure on different CRDs. Therefore, when planning for green development, more consideration must be given to public health and green management as intervention measures.https://www.crd.york.ac.uk/PROSPEROFILES/384029_STRATEGY_20230116.pdf.

An Ab Initio Neural Network Potential Energy Surface for the Dimer of Formic Acid and Further Quantum Tunneling Dynamics.

We construct a full-dimensional ab initio neural network potential energy surface (PES) for the isomerization system of the formic acid dimer (FAD). This is based upon ab initio calculations using the DLPNO-CCSD(T) approach with the aug-cc-pVTZ basis set, performed at over 14000 symmetry-unique geometries. An accurate fit to the obtained energies is generated using a general neural network fitting procedure combined with the fundamental invariant method, and the overall energy-weighted root-mean-square fitting error is about 6.4 cm-1. Using this PES, we present a multidimensional quantum dynamics study on tunneling splittings with an efficient theoretical scheme developed by our group. The ground-state tunneling splitting of FAD calculated with a four-mode coupled method is in good agreement with the most recent experimental measurements. The PES can be applied for further dynamics studies. The effectiveness of the present scheme for constructing a high-dimensional PES is demonstrated, and this scheme is expected to be feasible for larger molecular systems.

Mycobacterium xenopi related spine infections: A case report and systematic literature review.

Background and purpose: Nontuberculous mycobacteria (NTM) disease is an important infection disease throughout the world. Mycobacterium xenopi (M. xenopi) is a common NTM. Extrapulmonary infections due to M. xenopi, particularly spine infections, are a rare occurrence, but lack of research is cited as a constraint for implementing NTM control in such patients. The purposes of this paper are to describe a case of spondylodiscitis, to review the published literature on cases of M. xenopi spine infections, and to summarize the predisposing factors, diagnosis, and treatment of infection. Methods: A case of spondylodiscitis was caused by M. xenopi in a patient with systemic lupus erythematosus (SLE). Research was conducted using the PubMed, ScienceDirect, Embase, Wiley Online Library, and Scopus databases using the following search terms: "Mycobacterium xenopi", "vertebral", "spinal", "spondylodiscitis", "infection", and "osteomyelitis". Results: We retrieved 14 cases published before August 2022. The risk factors for infection were iatrogenic infections (3/14, 21.43%), SLE (4/14, 28.57%), AIDS (4/14, 28.57%), and immunocompetence without any comorbidities (3/14, 21.43%). The most common sites of infection were thoracic vertebrae (10/14, 71.43%) and lumbar vertebrae (4/14, 28.57%). A total of 14 cases were isolated and identified as M. xenopi from a toad by mycobacterial culture. The identification time was 55.00 ± 7.55 days (the present report identification time of metagenomic next generation sequencing (mNGS) was only 2 days). All patients were treated with antibiotic therapy, and the duration of treatment was 13.18 ± 2.13 months. Clarithromycin-based therapy showed a higher improvement rate (5/6, 83.33%). Surgical intervention was performed in 5 patients. Only 1 patient did not show any improvement after surgical treatment. Conclusion: M. xenopi spine infection in humans presents with atypical clinical symptoms. mNGS identification may be a good choice. M. xenopi may be considered in immunocompromised patients with spinal infection. We recommend a clarithromycin-containing regimen and prolonging the duration of treatment to ensure effectiveness.

A retrospective analysis of Q fever osteomyelitis in children, with recommendations.

Osteomyelitis in children due to Q fever is a rare occurrence. In this study, we review 25 pediatric cases of this disease entity. The mean age of these 25 patients was 3.7years (range, 2-7 years). The risk factor for infection was history of contact with animals, such as cattle and sheep (23/25, 92.0%). The most common sites of infection were foot and ankle (12/25, 48.0%). The diagnosis of Q fever was confirmed by serologic testing in 25 children. On PCR, Coxiella burnetii was detected in 17 cases and it was not detected in the remaining five cases. A total of 22 children were treated with antibiotics, of which 15 received surgical treatment. The composition and duration of treatment varied greatly. Only 18 patients achieved significant recovery of joint mobility after drug and/or surgical treatment. Our current literature review show that the clinical manifestations of Q fever osteomyelitis in children are atypical. In the absence of serological test results, mNGS identification may be a good option. Compared with the guidelines that recommend doxycycline combined with hydroxychloroquine, we recommend that ciprofloxacin-based treatment combined with rifampicin or sulfamethoxazole/trimethoprim should be preferred in children under the age of 8 years, and the need for performing combined surgical debridement and determining the treatment duration should be evaluated according to their actual clinical situation.

Reprogramming the Metabolic Network in Kluyveromyces lactis with a Transcriptional Switch for De Novo Lacto-N-biose Synthesis.

Lacto-N-biose (LNB) is a member of the human milk oligosaccharide (HMO) family and is synthesized via an enzymatic reaction in vitro with N-acetylglucosamine (GlcNAc) and cofactors. In this study, LNB was synthesized using a cell factory for the first time. First, three modules were constructed in Kluyveromyces lactis for producing LNB from lactose and GlcNAc without the addition of cofactors. Second, a de novo pathway was constructed in K. lactis for producing LNB from lactose without adding GlcNAc. Finally, a transcriptional switch was introduced into K. lactis to reprogram its metabolic network for improving the flux from GlcNAc-6-P to GlcNAc in the de novo pathway. Subsequently, a final LNB yield of 10.41 g/L, similar to the salvage pathway yield, was achieved through the de novo pathway. The engineered K. lactis provides a promising technology platform for the industrial scale production of LNB.

Global association of greenness exposure with risk of nervous system disease: A systematic review and meta-analysis.

Nervous system disease (NSD) is a global health burden with increasing prevalence in the last 30 years. There is evidence that greenness can improve nervous system health through a variety of mechanisms; however, the evidence is inconsistent. In the present systematic review and meta-analysis, we examined the relationship between greenness exposure and NSD outcomes. Studies on the relationship between greenness and NSD health outcomes published till July 2022 were searched in PubMed, Cochrane, Embase, Scopus, and Web of Science. In addition, we searched the cited literature and updated our search on Jan 20, 2023, to identify any new studies. We included human epidemiological studies that assess the association of greenness exposure with the risk of NSD. Greenness exposure was measured using NDVI (the normalized difference vegetation index) and the outcome was the mortality or morbidity of NSD. The pooled relative risks (RRs) were estimated using a random effects model. Of 2059 identified studies, 15 studies were included in our quantitative evaluation, in which 11 studies found a significant inverse relationship between the risk of NSD mortality or incidence/prevalence and an increase in surrounding greenness. The pooled RRs for cerebrovascular diseases (CBVD), neurodegenerative diseases (ND), and stroke mortality were 0.98 (95 % CI: 0.97, 1.00), 0.98 (95 % CI: 0.98, 0.99), and 0.96 (95 % CI: 0.93, 1.00), respectively. The pooled RRs for PD incidence and stroke prevalence/incidence were 0.89 (95 % CI: 0.78, 1.02) and 0.98 (95 % CI: 0.97, 0.99), respectively. The confidence of evidence for ND mortality, stroke mortality, and stroke prevalence/incidence was downgraded to "low", while CBVD mortality and PD incidence were downgraded to "very low" due to inconsistency. We found no evidence of publication bias and the sensitivity analysis results of all subgroups are robust except for the stroke mortality subgroup. This is the first comprehensive meta-analysis of greenness exposure and NSD outcomes in which an inverse relationship was observed. It is necessary to conduct further research to ascertain the role greenness exposure plays in various NSDs and the management of greenness should be considered a public health strategy.

Lenvatinib plus sintilimab versus lenvatinib monotherapy as first-line treatment for advanced HBV-related hepatocellular carcinoma: A retrospective, real-world study.

Background: The most common type of primary liver cancer is hepatocellular carcinoma (HCC), and hepatitis B virus (HBV)-related HCC accounts for many HCC cases and has a high mortality rate. The goal of our study was to investigate the efficacy and safety of lenvatinib plus sintilimab therapy in real-world practice and identify factors affecting long-term prognosis. Methods: A retrospective study was conducted with 139 consecutive patients with unresectable HCC treated with lenvatinib or lenvatinib plus sintilimab at the Fifth Medical Center of PLA General Hospital from June 2018 to June 2021. The 139 patients were divided into the control group (85 patients) and the combined treatment group (54 patients) according to the antitumour drugs used for treatment. Efficacy was determined using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the HCC-specific modified RECIST (mRECIST) for 139 patients who completed the 1st and second tumour assessments. Safety was evaluated in 60 patients in the combined treatment group and 90 patients in the control group using the Common Terminology Criteria for Adverse Events version 5.0. Results: A total of 139 male Chinese patients (49.6% ≥ 55 years old) were included in the efficacy analysis. The median overall survival in the combined treatment group was 21.7 months, and the median progression-free survival was 11.3 months. According to the mRECIST criteria, the objective response rate was 38.9%, and the disease control rate was 92.6%. The median overall survival (mOS), median progression-free survival (mPFS), overall response rate (ORR) and disease control rate (DCR) in the lenvatinib monotherapy group were 12.8 months, 6.6 months, 24.7%, and 74.1%, respectively. Hypertension was the most common adverse event in both groups. Some immune-related adverse events, such as hypothyroidism (n = 5), elevated blood creatinine (n = 3), elevated cardiac enzymes (n = 1), elevated amylase (n = 1) and increased fasting glucose (n = 1), occurred only in the combined therapy group. Five patients in the lenvatinib monotherapy group and six patients in the lenvatinib plus sintilimab group discontinued therapy due to severe adverse events (AEs) (grade 3). No ≥ 4-grade AEs occurred in any patients. Conclusion: The TKI lenvatinib combined with PD-1-targeted immunotherapy sintilimab is efficacious and safe in real-world practice and may lead to better long-term outcomes than lenvatinib alone.

Corrigendum to "Lenvatinib plus sintilimab versus lenvatinib monotherapy as first-line treatment for advanced HBV-related hepatocellular carcinoma: A retrospective, real-world study" [Heliyon 8 (6) (2022) e09538].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e09538.].