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Zhao-Li Zhang,1,&ast; Zhen Xu,2,&ast; Shi-Kun Yang,3 Jin-Gui Huang,2 Feng-Mei Huang,2 Yu-Mei Shi2 1Department of Nursing, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 2Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 3Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu-Mei Shi, Email 515342831@qq.comPurpose: The purpose of this study is to understand the level of quality of life (QOL) of lung cancer patients receiving immunotherapy and to clarify the potential mediating role of self-perceived burden (SPB) in the relationship between financial toxicity (FT) and QOL.Patients and Methods: A convenience sample of 342 lung cancer patients receiving immunotherapy was recruited from a cancer hospital from October 2022 to April 2023 for this cross-sectional study. The participants were requested to complete the following structured questionnaires: a sociodemographic and clinical questionnaire, the Functional Assessment of Cancer Therapy–Lung (FACT-L), the Self-Perceived Burden Scale (SPBS) and the COmprehensive Score for Financial Toxicity (COST). The data were subjected to Pearson correlation analysis and bootstrapping analysis in structural equation modelling.Results: The total FACT-L score was 79.90± 15.84 points in 322 lung cancer patients receiving immunotherapy. FT (β = 0.37, P < 0.01) and SPB (β = − 0.27, P < 0.01) had a direct effect on QOL. In addition, SPB partly mediated the association between FT and QOL, and the standardized indirect effect was 0.19, accounting for 33.9% of the total effect.Conclusion: The present study revealed that there is still much room for improvement in the QOL of lung cancer patients during immunotherapy. A greater financial burden resulted in a greater self-perceived burden and was thus associated with inferior QOL. It is imperative for oncology nurses to routinely assess QOL, FT or risk and SPB for lung cancer patients undergoing immunotherapy as well as to assist those patients in understanding the potential financial risk of each choice and help them take more active roles in their routine clinical care.Keywords: lung cancer, immunotherapy, quality of life, financial toxicity, self-perceived burden

Pyrrolizidine alkaloids (PAs) are a structurally diverse group of heterocyclic specialized metabolites characterized by a core structure comprising a hexahydro-1H-pyrrolizine. PAs are synthesized through two main pathways. In plants, assembly occurs via a homospermidine synthase, and in bacteria, through combined action of a nonribosomal peptide synthetase and a Baeyer-Villiger monooxygenase. While the toxic properties of plant-derived PAs and their prevalence in animal and human foods have been extensively studied, the biological roles and biosynthesis of more complex bacterial PAs are not well understood. Here, we report the identification and characterization of a bacterial biosynthetic gene cluster from Xenorhabdus hominickii, xhpA-G, which is responsible for producing the PA pseudo-dimer pyrrolizwilline. Analysis of X. hominickii promoter exchange mutants together with heterologous expression of xhpA-G in E. coli, revealed a set of pathway intermediates, two of which were chemically synthesized, as well as multiple derivatives. This information was leveraged to propose a detailed biosynthetic pathway to pyrrolizwilline. Furthermore, we have characterized the hydrolase XhpG, the key enzyme in the conversion of the pathway intermediate pyrrolizixenamide to pyrrolizwilline, using X-ray crystallography and small-angle X-ray scattering (SAXS)., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The bacterial cell membrane primarily houses lipids, carbohydrates, and proteins forming a barrier and interface that maintains cellular integrity, supports homeostasis, and senses environmental changes. Compared to lipid components and excreted secondary metabolites, compounds embedded in the producer cell membrane are often overlooked due to their low abundance and niche-specific functions. The accumulation of findings has led to an increased appreciation of their crucial roles in bacterial cell biochemistry, physiology, and ecology, as well as their impact on mutualistic and pathogenic bacteria-eukaryote interactions. This review highlights the structures, biosynthesis, regulation, and ecological functions of membrane-embedded secondary metabolites. It also discusses antibiotics that target their biosynthetic pathways, aiming to inspire the development of antibiotics specific to pathogenic bacteria without harming human cells., (© 2024 Wiley-VCH GmbH.)

Covering: up to March 2024.Microbial natural products have historically been a cornerstone for the discovery of therapeutic agents. Advanced (meta)genome sequencing technologies have revealed that microbes harbor far greater biosynthetic capabilities than previously anticipated. However, despite the application of CRISPR/Cas-based gene editing and high-throughput technologies to activate silent biosynthetic gene clusters, the rapid identification of new natural products has not led to a proportional increase in the discovery rate of lead compounds or drugs. A crucial issue in this gap may be insufficient knowledge about the inherent biological and physiological functions of microbial natural products. Addressing this gap necessitates recognizing that the generation of functional natural products is deeply rooted in the interactions between the producing microbes and other (micro)organisms within their ecological contexts, an understanding that is essential for harnessing their potential therapeutic benefits. In this review, we highlight the discovery of functional microbial natural products from diverse niches, including those associated with humans, nematodes, insects, fungi, protozoa, plants, and marine animals. Many of these findings result from an organismic-interaction-guided strategy using multi-omic approaches. The current importance of this topic lies in its potential to advance drug discovery in an era marked by increasing antimicrobial resistance.

The aim of this study was to comprehensively assess the causal relationship between the overall genetic effect of circulating ApoE levels and panvascular lesions using newer genome-wide association data and two-sample bidirectional Mendelian randomization (MR) analysis. Two-way MR using single-nucleotide polymorphisms of circulating ApoE as instrumental variables was performed using the highest-priority Genome-wide association study (GWAS) data, with factor-adjusted and data-corrected statistics, to estimate causal associations between circulating ApoE levels and 10 pan-vascular diseases in > 500,000 UK Biobank participants, > 400,000 participants of Finnish ancestry, and numerous participants in a consortium of predominantly European ancestry. Meta-analysis was conducted to assess positive results. After correcting for statistical results, elevated circulating ApoE levels were shown to have a significant protective effect against Cerebral ischemia (CI) [IVW odds ratio (OR) 0.888, 95% Confidence Interval (CI): 0.823-0.958, p = 2.3 × 10 -3 ], Coronary heart disease [IVW OR 0.950,95% CI: 0.924-0.976, p = 2.0 × 10 -4 ] had a significant protective effect and potentially suggestive protective causality against Angina pectoris [IVW odds ratio (OR) 0.961, 95%CI: 0.931-0.991, p = 1.1 × 10 -2 ]. There was a potential causal effect for increased risk of Heart failure (HF) [IVW ratio (OR) 1.040, 95%CI: 1.006-1.060, p = 1.8 × 10 -2 ]. (Bonferroni threshold p < 0.0026, P FDR  < 0.05) Reverse MR analysis did not reveal significant evidence of a causal effect of PVD on changes in circulating ApoE levels. Meta-analysis increases reliability of results. Elevated circulating ApoE levels were particularly associated with an increased risk of heart failure. Elevated ApoE levels reduce the risk of cerebral ischemia, coronary heart disease, and angina pectoris, reflecting a protective effect. The possible pathophysiological role of circulating ApoE levels in the development of panvascular disease is emphasized., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Raman scattering provides essential insights into phonons, electronic structures and electron-phonon coupling within solids through the intensity of Raman peaks, which cannot be easily quantified using the classical bond polarizability model. The interlayer bond polarizability model (IBPM) had been developed to understand the Raman intensity of layer-breathing modes (LBMs) in two-dimensional materials. However, the quantitative understanding of the LBM intensity of a van der Waals heterostructure (vdWH) remains challenging. Here, in polynary vdWHs comprising twisted multilayer graphene (tMLG), MoS 2 and hBN, we observed a series of LBMs, whose intensity is markedly dependent on the excitation energy and twist angle of the tMLG constituent. An improved IBPM is proposed to quantitatively understand the Raman intensity of LBMs in the tMLG-based vdWHs, including the emergence or absence of a specific LBM when the excitation energy is resonant with the electronic states of tMLG or MoS 2 constituents. This work underscores the significant potential of the improved IBPM in accurately understanding and predicting the intensity profile of LBM in polynary vdWHs, even for the case of Raman scattering with excitation energies selectively resonant with the electronic states of the corresponding specific constituents.

The discovery of novel bioactive compounds produced by microorganisms holds significant potential for the development of therapeutics and agrochemicals. In this study, we conducted genome mining to explore the biosynthetic potential of entomopathogenic bacteria belonging to the genera Xenorhabdus and Photorhabdus. By utilizing next-generation sequencing and bioinformatics tools, we identified novel biosynthetic gene clusters (BGCs) in the genomes of the bacteria, specifically plu00736 and plu00747. These clusters were identified as unidentified non-ribosomal peptide synthetase (NRPS) and unidentified type I polyketide synthase (T1PKS) clusters. These BGCs exhibited unique genetic architecture and encoded several putative enzymes and regulatory elements, suggesting its involvement in the synthesis of bioactive secondary metabolites. Furthermore, comparative genome analysis revealed that these BGCs were distinct from previously characterized gene clusters, indicating the potential for the production of novel compounds. Our findings highlighted the importance of genome mining as a powerful approach for the discovery of biosynthetic gene clusters and the identification of novel bioactive compounds. Further investigations involving expression studies and functional characterization of the identified BGCs will provide valuable insights into the biosynthesis and potential applications of these bioactive compounds., (© 2023. The Author(s).)

Three unusual sesterterpenoids featuring unprecedented rearranged colquhounane (C 25 ) and tetranorcolquhounane (C 21 ) frameworks, colquhounoids E ( 1 ) and F ( 3 ) and norcolquhounoid F ( 2 ), were isolated from a Lamiaceae medicinal plant Colquhounia coccinea var. mollis . Their structures were elucidated by spectroscopic analysis and quantum chemical calculations. A biomimetic inspired regioselective cyclopropane cleavage was achieved under acidic conditions. The immunosuppressive activities of these new sesterterpenoids were also evaluated.

Objective: To investigate the role of serum hepatitis B virus RNA (HBV RNA) in predicting HBeAg serological conversion in children with chronic hepatitis B. Methods: 175 children aged 1~17 years with chronic hepatitis B who received interferon α (IFNα) for 48 weeks were selected. Patients were divided into HBeAg seroconversion and non-conversion based on whether HBeAg seroconversion occurred at 48 weeks of treatment.T-test and Mann-Whitney U test were used to compare between groups; chisquare test or Fisher exact probability method was used to compare the frequency between groups of classified variables; and Pearson correlation was used to analyze the correlation between indicators. Univariate and multivariate logistic regression analyses were used to identify influencing factors associated with HBeAg serological conversion. The predictive effect of HBV RNA, HBV DNA, and HBsAg on HBeAg serological conversion was compared and analyzed by the receiver operating characteristic curve (ROC). Results: The seroconversion rate of HBeAg at 48 weeks was 36.0% (63/175). The reduction in HBVRNA levels from baseline to the 12th, 24th, 36th, and 48th weeks of antiviral therapy was significantly greater in the HBeAg serological conversion group than that in the non-conversion group, and the difference was statistically significant between the two groups (P < 0.05). Univariate and multivariate regression analyses showed that age and a decline in HBV RNA levels at week 12 were independent predictors of HBeAg serological conversion. The area under the ROC curve (AUROC) of HBV RNA decline at week 12 was 0.677(95% CI ∶0.549-0.806, P = 0.012), which was significantly better than the same period of AUROC of HBV DNA (0.657, 95% CI ∶0.527-0.788, P = 0.025) and HBsAg (0.660, 95% CI ∶0.526-0.795, P = 0.023) decline. HBV RNA levels decreased (>1.385 log10 copies/ml) at week 12, with a positive predictive value of 53.2%, a negative predictive value of 72.2%, a sensitivity of 77.4%, and a specificity of 57.9% for HBeAg seroconversion. Conclusion: HBV RNA level lowering during the 12th week of antiviral therapy can serve as an early predictor marker for HBeAg serological conversion in children with chronic hepatitis B.

Neurotransmitters (NTs) are essential for intercellular communication and primarily include monoamine, amino acid, and cholinergic NTs. These molecules play important roles in the body's stress response, motor coordination, neuronal communication, and homeostatic functions. Previous studies have shown that abnormal changes in NT levels are associated with various neurological disorders. Therefore, the development of accurate analytical methods for NT detection will enhance the current understanding on complex neuropathophysiology by providing functional knowledge and techniques for early diagnosis, thereby facilitating the development of new therapeutic options for the related diseases. The solid phase microextraction (SPME) technique combines sample preparation, separation, and enrichment in a single step and is minimally invasive, low cost, solvent free, and high throughput. SPME has been successfully applied to the in vivo analysis of target analytes in animal, human, and plant tissues. The coating material plays a significant role in the development of in vivo SPME methods and must meet various analytical requirements, including a suitable geometry for the SPME device, high extraction capacity, excellent selectivity, and wide extraction coverage for the target analytes. Covalent organic frameworks (COFs) are porous crystalline polymers constructed from organic framework units through strong covalent bonds; these materials are characterized with a low density, large specific surface area, permanent porosity, excellent chemical/thermal stability, and easy functionalization.In this study, a sulfonic acid-functionalized COF material (COF-SO 3 H) with good crystallinity, excellent chemical/thermal stability, strong hydrophobicity, a uniform mesoporous structure, and narrow pore size distribution was prepared using 2,4,6-triformylphloroglucinol and 1,4-diamino-2-nitrobenzene as monomers. Then, the COF-SO 3 H was coated onto the surface of stainless-steel fibers and used for in vivo enrichment of NTs. The structural properties of COF-SO 3 H were characterized using various techniques, such as scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FT-IR), and X-ray diffraction (XRD), all of which showed that COF-SO 3 H had a good crystalline structure and uniform mesopore distribution with a specific surface area of 46.17 m 2 /g. Compared with the SPME fibers of HLB, C18, MCX, amino, and PXC columns, the prepared COF-SO 3 H fibers showed better extraction efficiency for the target NTs. Next, the factors affecting SPME efficiency were optimized. The optimal desorption solvent was formic acid-methanol-water (0.5∶49.5∶50, v/v/v), and the optimal extraction and desorption times were 15 min. A method for the in vivo analysis of NTs in the brains of mice was established by combining the COF-SO 3 H fibers with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) under optimal conditions. The NTs were separated on an Acquity UPLC BEH-C18 analytical column (100 mm×2.1 mm, 1.7 μm) with 0.1% formic acid aqueous solution (A) and acetonitrile (B) as the mobile phases. The flow rate was set to 0.2 mL/min, and the gradient elution procedure was as follows: 0-4 min, 5%B-6%B; 4-7 min, 6%B-5%B; 7-11 min, 5%B. Under optimal conditions, the method showed good linearity ( r 2 >0.99). The limits of quantification ( S/N ≥5) were in the range of 0.003-0.005 μg/mL and 3-5 μg/mL for monoamine and amino acid NTs, respectively, with RSDs of less than 20%. The method showed good precision (0.80%-9.70%) and accuracy (2.08%-17.72%), with absolute matrix effects in the range of 82.22%-117.92%. These values reflect the good purification and enrichment abilities of the proposed fibers for the target analytes. Finally, the established SPME method was combined with UPLC-MS/MS and successfully applied to quantify target NTs in the brains of mice. The proposed strategy provides a practical method for the in vivo detection and quantitative analysis of NTs and expands the applications of functionalized COF materials for the analysis of various targets.

A male infant, aged 1 month and 14 days, was admitted to the hospital due to abdominal distension lasting for 2 weeks and worsening for 3 days. The infant had a history of omphalitis. Physical examination revealed severe abdominal distension, prominent abdominal wall veins, hepatosplenomegaly, and massive ascites. There was a slight elevation in liver transaminase levels. Liver ultrasound and CT scans demonstrated the absence of visualization of the intrahepatic segment of the portal vein and the left, middle, and right veins of the liver, indicating occlusion of these vessels, along with surrounding fibrous hyperplasia. The clinical diagnosis was hepatic sinusoidal obstruction syndrome resulting from omphalitis. A large amount of bloody ascites developed after 12 days of hospitalization, resulting in hypovolemic shock and respiratory failure. The infant passed away following the family's decision to discontinue treatment. This article focuses on the diagnostic approach and multidisciplinary management of neonatal-onset hepatic sinusoidal obstruction syndrome, as well as provides insights into the differential diagnosis of hepatomegaly and ascites.

Background: Cataracts remain a prime reason for visual disturbance and blindness all over the world, despite the capacity for successful surgical replacement with artificial lenses. Diabetic cataract (DC), a metabolic complication, usually occurs at an earlier age and progresses faster than age-related cataracts. Evidence has linked N6-methyladenosine (m6A) to DC progression. However, there exists a lack of understanding regarding RNA m6A modifications and the role of m6A in DC pathogenesis., Aim: To elucidate the role played by altered m6A and differentially expressed mRNAs (DEmRNAs) in DC., Methods: Anterior lens capsules were collected from the control subjects and patients with DC. M6A epitranscriptomic microarray was performed to investigate the altered m6A modifications and determine the DEmRNAs. Through Gene Ontology and pathway enrichment (Kyoto Encyclopedia of Genes and Genomes) analyses, the potential role played by dysregulated m6A modification was predicted. Real-time polymerase chain reaction was further carried out to identify the dysregulated expression of RNA methyltransferases, demethylases, and readers., Results: Increased m6A abundance levels were found in the total mRNA of DC samples. Bioinformatics analysis predicted that ferroptosis pathways could be associated with m6A-modified mRNAs. The levels of five methylation-related genes- RBM15 , WTAP , ALKBH5 , FTO , and YTHDF1 -were upregulated in DC samples. Upregulation of RBM15 expression was verified in SRA01/04 cells with high-glucose medium and in samples from DC patients., Conclusion: M6a mRNA modifications may be involved in DC progression via the ferroptosis pathway, rendering novel insights into therapeutic strategies for DC., Competing Interests: Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, has shifted lung cancer treatment from empirical chemotherapy to targeted molecular therapy. However, acquired drug resistance is inevitable in almost all non-small cell lung cancer (NSCLC) patients treated with gefitinib. Combined treatment with dihydroartemisinin (DHA) and gefitinib produced a better inhibitory effect on lung adenocarcinoma than gefitinib treatment alone; however, the specific mechanism remains unclear. In this study, we aimed to assess the underlying mechanism of this combination treatment. We prepared gefitinib-resistant A549 cells and investigated whether apoptosis and ferroptosis were involved in the sensitizing effect of DHA. Treatment with 5 μM gefitinib resulted in rupturing and floatation of A549 cells in the medium, while A549-GR cells were found to be insusceptible to gefitinib. However, treatment with DHA substantially inhibited the proliferation of A549-GR cells in a dose-dependent manner accompanied by increased apoptosis and ferroptosis. The accumulated reactive oxygen species (ROS) was crucial for the inhibitory effect of DHA on A549-GR cells. Moreover, cellular autophagy was significantly upregulated post-DHA treatment. The combined treatment of DHA and gefitinib resulted in inhibition of proliferation of A549, H1975, and HCC827 cells, and ROS accumulation and a remarkable induction of apoptosis was observed in A549-GR cells. DHA significantly induced apoptosis and ferroptosis in a dose-dependent manner and exhibited high cellular toxicity on A549-GR cells when combined with gefitinib., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P <0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P <0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t =4.760, P <0.001] and the proportion of patients with SF levels of ≥100 μg/L ( P =0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P =0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

To investigate the effect of Huazhi Rougan Granules(HZRG) on autophagy in a steatotic hepatocyte model of free fatty acid(FFA)-induced nonalcoholic fatty liver disease(NAFLD) and explore the possible mechanism. FFA solution prepared by mixing palmitic acid(PA) and oleic acid(OA) at the ratio of 1∶2 was used to induce hepatic steatosis in L02 cells after 24 h treatment, and an in vitro NAFLD cell model was established. After termination of incubation, cell counting kit-8(CCK-8) assay was performed to detect the cell viability; Oil red O staining was employed to detect the intracellular lipid accumulation; enzyme-linked immunosorbnent assay(ELISA) was performed to measure the level of triglyceride(TG); to monitor autophagy in L02 cells, transmission electron microscopy(TEM) was used to observe the autophagosomes; LysoBrite Red was used to detect the pH change in lysosome; transfection with mRFP-GFP-LC3 adenovirus was conducted to observe the autophagic flux; Western blot was performed to determine the expression of autophagy marker LC3B-Ⅰ/LC3B-Ⅱ, autophagy substrate p62 and silent information regulator 1(SIRT1)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway. NAFLD cell model was successfully induced by FFA at 0.2 mmol·L~(-1) PA and 0.4 mmol·L~(-1) OA. HZRG reduced the TG level(P&lt;0.05, P&lt;0.01) and the lipid accumulation of FFA-induced L02 cells, while elevated the number of autophagosomes and autophagolysosomes to generate autophagic flux. It also affected the functions of lysosomes by regulating their pH. Additionally, HZRG up-regulated the expression of LC3B-Ⅱ/LC3B-Ⅰ, SIRT1, p-AMPK and phospho-protein kinase A(p-PKA)(P&lt;0.05, P&lt;0.01), while down-regulated the expression of p62(P&lt;0.01). Furthermore, 3-methyladenine(3-MA) or chloroquine(CQ) treatment obviously inhibited the above effects of HZRG. HZRG prevented FFA-induced steatosis in L02 cells, and its mechanism might be related to promoting autophagy and regulating SIRT1/AMPK signaling pathway.

Goals: To assess the efficacy and safety of Chinese Medicine Prescription "W-LHIT" in subjects with simple obesity, and to explore its potential mechanism of action., Methods: Thirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the "W-LHIT" capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding., Results: 72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group ( p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group ( p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium , and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment., Conclusion: W-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications., Competing Interests: This study shared the US Patent No: US20160296573A1 Weight loss formulations, methods, and compositions based on Traditional Chinese Medicine by X-ML, DC, etc. Author DC was employed by Healthy Freedom LLC. Authors NY and K.S are members of General Nutraceutical Technology LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cao, Wei, Wen, Song, Srivastava, Yang, Shi, Miao, Chung and Li.)

Background: To systematically evaluate the quality of the guidelines for the diagnosis and treatment of Helicobacter pylori infection and to analyze the differences and reasons for the key recommendations in the guidelines., Methods: Databases and websites were systematically searched to obtain guidelines for the diagnosis and treatment of Helicobacter pylori infection. Four independent reviewers used the Guideline Evaluation Tool (AGREE II) to evaluate the included guidelines. The intraclass correlation coefficient (ICC) and Fleiss' kappa coefficient were used to measure the consistency of evaluation guidelines between guide reviewers. Differences between guidelines and the reasons for the differences were analyzed by comparing the recommendations of different guidelines and the evidence supporting the recommendations., Results: A total of 17 guidelines for Helicobacter pylori infection were included in this study. The AGREE II scores of these guidelines were low overall, with 4 of them had a score of over 60%, which indicates that the guidelines are recommended, and 13 of them having a score ranging from 30 to 60%, which indicates that the guidelines are recommended but need to be revised, while no guideline had a score of 30% or less, which indicates that they were not recommended. The analysis of these guidelines found that there were some differences in the main recommendations. Not all guidelines recommend sequential therapy as the recommended therapy. Whether bismuth quadruple therapy should be used as the recommended first-line therapy is unclear. The antibiotic resistance rate is different in different regions. Combined with the local antibiotic sensitivity test, the eradication rate of Helicobacter pylori can be improved., Conclusion: There are significant differences in the quality of Helicobacter pylori infection guidelines and the key recommendations. Improving the deficiencies of existing guidelines is an effective way to develop high-quality guidelines and make reasonable recommendations for the treatment of Helicobacter pylori infection in the future., (© 2022 John Wiley & Sons Ltd.)

Objective: To explore the influence and significance of respiratory filter on the judgment of pulmonary function and the conclusion of occupational health examination in occupational health examination. Methods: From August to November 2020, 252 occupational health examinees were randomly selected as the research objects, and the lung function was examined with the respiratory filter bite and the straight cylinder bite without filter, respectively. The lung function examination indexes and the qualification rate of lung function examination were analyzed and compared between the two groups, and the diagnostic criteria of lung function examination was corrected. Results: 252 subjects were 36 (30, 42) years old. The qualified rate of lung function examination with respiratory filter bite (28.17%, 71/252) was lower than that with straight cylinder bite (34.92%, 88/252) , the difference was statistically significant ( P <0.05) . The percentage of forced vital capacity in normal predicted value (FVC%) , percentage of forced expiratory volume in the first second in normal predicted value (FEV(1)%) , and percentage of forced expiratory volume in the first second in forced vital capacity (FEV(1)/FVC%) of subjects using respiratory filter bite were lower than those using the straight cylinder bite ( P <0.05) . The corrected diagnostic criteria of pulmonary function were FVC%>78%, FEV(1)%>77%, FEV(1)/FVC%>68%. There was no significant difference between the qualified rate of the respiratory filter bite lung function test calculated according to the corrected diagnostic criteria (35.71%, 90/252) and the qualified rate of the straight cylinder bite lung function test calculated according to the original diagnostic criteria (34.92%, 88/252) ( P >0.05) . Conclusion: In occupational health examination, the use of respiratory filter may affect the results of pulmonary function examination. The diagnostic criteria of pulmonary function can be corrected according to different filtering effects to ensure the accuracy of the conclusions of occupational health examination.

Public health studies indicate that artificial light is a high-risk factor for metabolic disorders. However, the neural mechanism underlying metabolic modulation by light remains elusive. Here, we found that light can acutely decrease glucose tolerance (GT) in mice by activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) innervating the hypothalamic supraoptic nucleus (SON). Vasopressin neurons in the SON project to the paraventricular nucleus, then to the GABAergic neurons in the solitary tract nucleus, and eventually to brown adipose tissue (BAT). Light activation of this neural circuit directly blocks adaptive thermogenesis in BAT, thereby decreasing GT. In humans, light also modulates GT at the temperature where BAT is active. Thus, our work unveils a retina-SON-BAT axis that mediates the effect of light on glucose metabolism, which may explain the connection between artificial light and metabolic dysregulation, suggesting a potential prevention and treatment strategy for managing glucose metabolic disorders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Rheumatoid arthritis(RA) is an autoimmune disease that seriously affects the physical and mental health of patients, but its pathogenesis is still unclear. At present, clinical treatment drugs include conventional synthetic disease modifing anti-rheumatic drugs(csDMARDs), nonsteroid anti-inflammtory drugs(NSAIDs), hormones, small molecule targeted drugs, biological agents, etc. These drugs can relieve the clinical symptoms of most patients with RA to a certain extent, but there are still many limitations, such as drug adverse reactions and individual differences in drug efficacy. Therefore, the research on drug treatment targets and the development of low-toxicity drugs helps further improve the precise prevention, diagnosis, and treatment of RA. There is an urgent need for efficient and low-toxic treatments to delay the clinical progress of RA. As a treasure of Chinese culture, traditional Chinese medicine(TCM) is widely used as an alternative therapy in the treatment of various diseases, and has a significant clinical efficacy. TCM therapy(including monomer traditional Chinese medicine, classical compounds, and non-drug therapies) has a significant curative effect on RA. Based on the literature research in recent years, this paper reviewed the clinical and mechanism research of TCM therapy in the treatment of RA, and provided more in-depth thinking for the wide application of TCM therapy in clinical practice.

Benzoxazolinate is a rare bis-heterocyclic moiety that interacts with proteins and DNA and confers extraordinary bioactivities on natural products, such as C-1027. However, the biosynthetic gene responsible for the key cyclization step of benzoxazolinate remains unclear. Herein, we show a putative acyl AMP-ligase responsible for the last cyclization step. We used the enzyme as a probe for genome mining and discovered that the orphan benzobactin gene cluster in entomopathogenic bacteria prevails across Proteobacteria and Firmicutes. It turns out that Pseudomonas chlororaphis produces various benzobactins, whose biosynthesis is highlighted by a synergistic effect of two unclustered genes encoding enzymes on boosting benzobactin production; the formation of non-proteinogenic 2-hydroxymethylserine by a serine hydroxymethyltransferase; and the types I and II NRPS architecture for structural diversity. Our findings reveal the biosynthetic potential of a widespread benzobactin gene cluster., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

ESKAPE pathogens, as priority 1 and 2 pathogens, are prevalent infectious agents associated with high morbidity and mortality. ESKAPE can cause broad-spectrum diseases with increasing tendency of resistance acquisition to antibiotics and have enhanced the urge for the development of alternate therapeutics. 1,2,3-Triazole, a highly privileged moiety for the discovery of novel drugs, not only can act as a linker to tether different pharmacophores, but also can serve as a pharmacophore. Notably, several 1,2,3-triazole-containing hybrids which are exemplified by cefatrizine, radezolid and tazobactam have already approved as antibiotics to treat infections caused by various organisms including ESKAPE pathogens and their drug-resistant forms, revealing that 1,2,3-triazole-containing hybrids are useful prototypes for clinical deployment in the control of bacterial infections. The purpose of the present review article is to provide an emphasis on the current scenario (2018-2022) of 1,2,3-triazole-containing hybrids with potential antibacterial activity against ESKAPE pathogens to facilitate further rational design of more effective candidates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

To assess the independent and joint associations between cardiorespiratory fitness (CRF), screen time and mental health among Chinese school-aged children, a cross-sectional study was conducted in 3 primary schools in Wuhan city, China. Children self-reported ST, and their height, weight and CRF were measured. Mental health (anxiety, depressive symptom, and self-esteem) was assessed by self-administered questionnaires. A total of 805 children aged 9.1 ± 0.6 years participated in this study. High ST was associated with significantly increased risk for anxiety and low self-esteem, while high CRF was associated with a decreased risk of low self-esteem. In the joint model, children with low ST and high CRF showed the lowest risk for anxiety (OR: 0.42, 95%CI: 0.20-0.89) and low self-esteem (OR:0.44, 95%CI: 0.24-0.82). High ST and low CRF were negatively associated with mental health in Chinese schoolchildren. Health care and interventions on limiting ST and improving CRF level are warranted to promote the mental health in this population., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Piscibactins and photoxenobactins are metallophores and virulence factors, whose biosynthetic gene cluster, termed pxb , is the most prevalent polyketide synthase/non-ribosomal peptide synthetase hybrid cluster across entomopathogenic bacteria. They are structurally similar to yersiniabactin, which contributes to the virulence of the human pathogen Yersinia pestis . However, the pxb -derived products feature various chain lengths and unusual carboxamide, thiocarboxylic acid, and dithioperoxoate termini, which are rarely found in thiotemplated biosyntheses. Here, we characterize the pxb biosynthetic logic by gene deletions, site-directed mutagenesis, and isotope labeling experiments. Notably, we propose that it involves (1) heterocyclization domains with various catalytic efficiencies catalyzing thiazoline and amide/thioester bond formation and (2) putative C-N and C-S bond cleavage off-loading manners, which lead to products with different chain lengths and usual termini. Additionally, the post-assembly-line spontaneous conversions of the biosynthetic end product contribute to production titers of the other products in the culture medium. This study broadens our knowledge of thiotemplated biosynthesis and how bacterial host generate a chemical arsenal.

Microorganisms contribute to the biology and physiology of eukaryotic hosts and affect other organisms through natural products. Xenorhabdus and Photorhabdus (XP) living in mutualistic symbiosis with entomopathogenic nematodes generate natural products to mediate bacteria-nematode-insect interactions. However, a lack of systematic analysis of the XP biosynthetic gene clusters (BGCs) has limited the understanding of how natural products affect interactions between the organisms. Here we combine pangenome and sequence similarity networks to analyse BGCs from 45 XP strains that cover all sequenced strains in our collection and represent almost all XP taxonomy. The identified 1,000 BGCs belong to 176 families. The most conserved families are denoted by 11 BGC classes. We homologously (over)express the ubiquitous and unique BGCs and identify compounds featuring unusual architectures. The bioactivity evaluation demonstrates that the prevalent compounds are eukaryotic proteasome inhibitors, virulence factors against insects, metallophores and insect immunosuppressants. These findings explain the functional basis of bacterial natural products in this tripartite relationship., (© 2022. The Author(s).)

Objective: The aim of the study was to construct and validate 18F-fluorodeoxyglucose (18F-FDG) PET-based radiomics nomogram and use it to predict N2-3b lymph node metastasis in Chinese patients with gastric cancer (GC)., Methods: A total of 127 patients with pathologically confirmed GC who underwent preoperative 18F-FDG PET/CT imaging between January 2014 and September 2020 were enrolled as subjects in this study. We use the LIFEx software to extract PET radiomic features. A radiomics signature (Rad-score) was developed with the least absolute shrinkage and selection operator algorithm. Then a prediction model, which incorporated the Rad-score and independent clinical risk factors, was constructed and presented with a radiomics nomogram. Receiver operating characteristic (ROC) analysis was used to assess the performance of Rad-score and the nomogram. Finally, decision curve analysis (DCA) was applied to evaluate the clinical usefulness of the nomogram., Results: The PET Rad-score, which includes four selected features, was significantly related to pN2-3b (all P < 0.05). The prediction model, which comprised the Rad-score and carcinoembryonic antigen (CEA) level, showed good calibration and discrimination [area under the ROC curve: 0.81(95% confidence interval: 0.74-0.89), P < 0.001)]. The DCA also indicated that the prediction model was clinically useful., Conclusion: This study presents a radiomics nomogram consisting of a radiomics signature based on PET images and CEA level that can be conveniently used for personalized prediction of high-risk N2-3b metastasis in Chinese GC patients., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Sapindus mukorossi  Gaertn is also known as Mu Huanzi, You Huanzi, soap tree, etc. The pericarp of  Sapindus mukorossi  contains many saponins, which is a type of natural non-ionic surfactant. Its extract has vigorous surface activity and biological activities such as bacteriostasis, oxidation resistance, and free radical scavenging. The  Sapindus mukorossi  extract is an environmentally friendly washing product that microorganisms can be rapidly decompose in nature without any environmental pollution.This study aims to investigate the effects of E-beam and Co 60 -γ irradiation on the total saponins content in the crude extract of the  S mukorossi . The  S mukorossi  powder is irradiated with E-beam and Co 60 -γ ray at doses of 0, 4, 6, 8, 10, and 12 kGy for E-beam and 0, 50, 100, 150, and 200 Gy, respectively, for Co 60 -γ ray. The changes in the content of total saponins in the crude extract, total detergency, and the bacteriostatic abilities before and after the irradiation were analyzed. The results showed that the content of total saponins in samples irradiated by E-beam was significantly higher than that in non-irradiated samples. The saponins yield was the highest at a radiation dose of 6 kGy, and the detergency and bacteriostatic ability were also the strongest. After low-dose Co 6 -γ irradiation, the total saponins in the  S mukorossi  crude extract, and detergency and bacteriostatic ability had no apparent change. Conclusion: E-beam irradiation at a dose of 6 kGy can effectively improve the content of total saponins in the crude extract of  S mukorossi  powder. In addition, its effects on detergency and bacteriostatic abilities are relatively significant. The findings provide sufficient reference data for the further development of  S mukorossi  commodities., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Sublobar resection is not suitable for patients with pathological invasiveness [including lymph node metastasis (LNM), visceral pleural invasion (VPI), and lymphovascular invasion (LVI)] of peripheral clinical T1 (cT1) non-small cell lung cancer (NSCLC), while primary tumor maximum standardized uptake value (SUV max ) on 18 F-FDG PET-CT is related to pathological invasiveness, the significance differed among different institutions is still challenging. This study explored the relationship between the tumor-to-blood standardized uptake ratio (SUR) of 18 F-FDG PET-CT and primary tumor pathological invasiveness in peripheral cT1 NSCLC patients., Methods: This retrospective study included 174 patients with suspected lung neoplasms who underwent preoperative 18 F-FDG PET-CT. We compared the differences of the clinicopathological variables, metabolic and morphological parameters in the pathological invasiveness and less-invasiveness group. We performed a trend test for these parameters based on the tertiles of SUR. The relationship between SUR and pathological invasiveness was evaluated by univariate and multivariate logistics regression models (included unadjusted, simple adjusted, and fully adjusted models), odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. A smooth fitting curve between SUR and pathological invasiveness was produced by the generalized additive model (GAM)., Results: Thirty-eight point five percent of patients had pathological invasiveness and tended to have a higher SUR value than the less-invasiveness group [6.50 (4.82-11.16) vs. 4.12 (2.04-6.61), P<0.001]. The trend of SUV max , mean standardized uptake value (SUV mean ), metabolic tumor volume (MTV), total lesion glycolysis (TLG), mean CT value (CT mean ), size of the primary tumor, neuron-specific enolase (NSE), the incidence of LNM, adenocarcinoma (AC), and poor differentiation in the tertiles of SUR value were statistically significant (P were <0.001, <0.001, 0.010, <0.001, <0.001, 0.002, 0.033, <0.001, 0.002, and <0.001, respectively). Univariate analysis showed that the risk of pathological invasiveness increased significantly with increasing SUR [OR: 1.13 (95% CI: 1.06-1.21), P<0.001], and multivariate analysis demonstrated SUR, as a continuous variable, was still significantly related to pathological invasiveness [OR: 1.09 (95% CI: 1.01-1.18), P=0.032] after adjusting for confounding covariates. GAM revealed that SUR tended to be linearly and positively associated with pathological invasiveness and E-value analysis suggested robustness to unmeasured confounding., Conclusions: SUR is linearly and positively associated with primary tumor pathological invasiveness independent of confounding covariates in peripheral cT1 NSCLC patients and could be used as a supplementary risk maker to assess the risk of pathological invasiveness., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-21-394). The authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objectives: We explored the relationship between lymph node metastasis (LNM) and total lesion glycolysis (TLG) of primary lesions determined by 18fluoro-2-deoxyglucose PET/computed tomography (18F-FDG PET/CT) in patients with gastric adenocarcinoma, and evaluated the independent effect of this association., Methods: This retrospective study included 106 gastric adenocarcinoma patients who were examined by preoperative 18F-FDG PET/CT imaging between April 2016 and April 2020. We measured TLG of primary gastric lesions and evaluated its association with LNM. Multivariate logistic regression and a two-piece-wise linear regression were performed to evaluate the relationship between TLG of primary lesions and LNM., Results: Of the 106 patients, 75 cases (71%) had LNM and 31 cases (29%) did not have LNM. Univariate analyses revealed that a per-SD increase in TLG was independently associated with LNM [odds ratio (OR) = 2.37; 95% confidence interval (CI), 1.42-3.98; P = 0.0010]. After full adjustment of confounding factors, multivariate analyses exhibited that TLG of primary lesions was still significantly associated with LNM (OR per-SD: 2.20; 95% CI, 1.16-4.19; P = 0.0164). Generalized additive model indicated a nonlinear relationship and saturation effect between TLG of primary lesions and LNM. When TLG of primary lesions was <23.2, TLG was significantly correlated with LNM (OR = 1.26; 95% CI, 1.07-1.48; P = 0.0053), whereas when TLG of primary lesions was ≥ 23.2, the probability of LNM was greater than 60%, gradually reached saturation effect, as high as 80% or more., Conclusions: In this preliminary study, there were saturation and segmentation effects between TLG of primary lesions determined by preoperative 18F-FDG PET/CT and LNM. When TLG of primary lesions was ≥ 23.2, the probability of LNM was greater than 60%, gradually reached saturation effect, as high as 80% or more. TLG of primary lesions is helpful in the preoperative diagnosis of LNM in patients with gastric adenocarcinoma., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The diameters of the vertebral arteries on both sides are usually asymmetrical. Vertebral artery dominance (VAD) and congenital vertebral artery dysplasia are derived from the asymmetry of the vertebral artery diameters on both sides. They are usually regarded as normal congenital vascular variations and have no practical clinical significance., Summary: Recently, several clinical studies have found that VAD is a risk factor for posterior circulation ischemic stroke (PCIS). The existence of VAD is clinically significant for the occurrence of PCIS, and it is recognized by an increasing number of clinicians., Key Messages: This article reviews the frequency and evaluation methods of VAD, its correlation with PCIS, and its mechanism., (© 2022 S. Karger AG, Basel.)

Strain W712 T was isolated from rhizosphere soil of Nicotiana tabacum L. collected from Kunming, south-west China. Cells were Gram-staining negative, aerobic, motile and rod shaped. The isolate grew at 20-45 °C (optimum 30 °C), pH 6.0-8.0 (optimum pH 7.0) and in the presence of up to 3.0% (w/v) NaCl (optimum 1%, w/v). Ubiquinone-10 was the only respiratory quinone type. Polar lipids contained diphosphatidylglycerol, phosphatidylmehtylethanolamine, phosphatidylglycerol, phosphatidylcholine and an unidentified aminolipid. The major fatty acids were detected as summed feature 8 (C 18:1 ω7c or C 18:1 ω6c), summed feature 3 (C 16:1 ω7c or C 16:1 ω6c) and C 18:1 2OH. The genomic DNA G + C content was 68.7%. The ANI values were 94.3%, 93.3% and 93.6% between Azospirillum baldaniorum Sp245 T , Azospirillum brasilense ATCC 49958 T , Azospirillum formosense CC-Nfb-7 T and strain W712 T , respectively, which were lower than the prokaryotic species delineation threshold of 95.0-96.0%. The digital DNA-DNA hybridization values between A. baldaniorum Sp245 T , A. brasilense ATCC 49958 T , A. formosense CC-Nfb-7 T and strain W712 T indicated that the candidate represents a novel genomic species. According to the phenotypic and genotypic characteristics, we propose that strain W712 T warrants the assignment to a novel species, for which the name Azospirillum tabaci sp. nov. (type strain W712 T  = CGMCC 1.18567 T  = KCTC 82186 T ) is proposed., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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Background: To establish a prediction of HBsAg seroconversion in children with chronic hepatitis B (CHB), so as to help clinicians to choose therapeutic strategy., Methods: A total of 63 children with HBeAg-positive CHB aged 1 to 17 years, who admitted to the fifth medical center of Chinese PLA general hospital and treated with interferon α (IFNα) 48 weeks were enrolled, the clinical data were measured. Based on the results of HBsAg seroconversion (HBsAg < 0.05 IU/mL and anti-HBsAg > 10 IU/L) at week 48, the patients were divided into HBsAg seroconversion (S) group and non-HBsAg seroconversion (NS) group. Multivariate COX regression was used to identify the impact factors associated with HBsAg seroconversion. A novel prediction index was established and the area under the receiver operating characteristic curve (AUROC) was used to assess the prediction for HBsAg seroconversion., Results: The 63 patients were divided into S group (20.6%, 13/63) and NS group (79.4%, 50/63). Univariate and multivariate analysis identified age, baseline intrahepatic cccDNA and serum HBsAg levels were independent impact factors for HBsAg seroconversion. Intrahepatic cccDNA was positively correlated with serum HBsAg (r = 0.464, p = 0.000). AUROC of HBV cccDNA was 0.83 (95% CI 0.71 to 0.95) and AUROC of baseline HBsAg was 0.77 (95% CI 0.61 to 0.92). Intrahepatic cccDNA ≤ 0.08 log 10 copies/10 6 cell is regarded as cutoff value, the positive predictive value(PPV) and negative predictive value(NPV) for HBsAg seroconversion were 86.8% and 60.0%, respectively, with a sensitivity of 92.0% and specificity of 56.2%. HBsAg ≤ 3.68 log 10 IU/mL is used as cut off value, the PPV and NPV for HBsAg seroconversion were 91.2% and 56.3%, respectively; the sensitivity and specificity was 86.0% of 69.2%, respectively. There was no statistical difference between them for predicting HBsAg seroconversion (p = 0.146)., Conclusions: HBsAg seroconversion can be predicted by the baseline serum HBsAg or intrahepatic cccDNA in children with CHB. Using the index, clinicians can choose more reasonable therapeutic strategy and reduce the waste of medical resources., (© 2021. The Author(s).)

Background: Sublobar resection is suitable for peripheral cT1N0M0 non-small-cell lung cancer (NSCLC). The traditional PET-CT criterion (lymph node size ≥1.0 cm or SUVmax ≥2.5) for predicting lymph nodes metastasis (LNM) has unsatisfactory performance., Objective: We explore the clinical role of preoperative SUVmax and the size of the primary lesions for predicting peripheral cT1 NSCLC LNM., Methods: We retrospectively analyzed 174 peripheral cT1 NSCLC patients underwent preoperative 18F-FDG PET-CT and divided into the LNM and non-LNM group by pathology. We compared the differences of primary lesions' baseline characteristics between the two groups. The risk factors of LNM were determined by univariate and multivariate analysis, and we assessed the diagnostic efficacy with the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value (NPV)., Results: Of the enrolled cases, the incidence of LNM was 24.7%. The preoperative SUVmax >6.3 or size >2.3 cm of the primary lesions were independent risk factors of peripheral cT1 NSCLC LNM (ORs, 95% CIs were 6.18 (2.40-15.92) and 3.03 (1.35-6.81). The sensitivity, NPV of SUVmax >6.3 or size >2.3 cm of the primary lesions were higher than the traditional PET-CT criterion for predicting LNM (100.0 vs. 86.0%, 100.0 vs. 89.7%). A Hosmer-Lemeshow test showed a goodness-of-fit (P = 0.479)., Conclusions: The excellent sensitivity and NPV of preoperative of the SUVmax >6.3 or size >2.3 cm of the primary lesions based on 18F-FDG PET-CT might identify the patients at low-risk LNM in peripheral cT1 NSCLC., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate the clinical and serological features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) overlap syndrome (Rhupus syndrome)., Methods: We retrospectively reviewed the medical records of 21 patients with Rhupus syndrome who were hospitalized at Department of Rheumatology and Immunology, People's Hospital of Xinjiang Uygur Autonomous Region between January 2010 and January 2018. We compared the joint involvement, autoantibodies and clinical manifestations of Rhupus syndrome with 81 cases of RA-alone and 51 cases of SLE-alone., Results: In 21 patients with Rhupus syndrome, there are 3 males and 18 females. Compared with the SLE-alone group, the patients with Rhupus syndrome were older [(49.43±11.66) vs. (40.59±12.73), P =0.008]. The median age of the patients with Rhupus syndrome at RA onset was significantly younger than that of the RA-alone patients [(32.58±11.14) vs. (43.11±11.83), P =0.010]. Of the 21 patients with Rhupus syndrome, the initial diagnosis was RA in 57% (12/21), except 2 male patients, the other 10 patients with SLE manifestations were menopause, the mean age of amenorrhea or menopause was (44.30±5.33) (36-50) years. The mean interval between the onset of SLE and RA was 10.83 years. Two patients started with SLE manifestations. Moreover, both diseases simultaneously developed in 33.3% of the patients. Except one male patient, 3 patients were in menopause stage when RA and SLE appeared. The positive rate of specific antibody Rhupus syndrome was similar to that of RA. Renal damage was relatively rare in SLE related manifestations, but the incidence of interstitial lung disease was higher. There were no significant differences in the prevalence of complements C3 and C4, antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), anti-SSA or anti-SSB antibody between the Rhupus syndrome and SLE-alone group., Conclusion: Rhupus syndrome is an overlapping syndrome in which RA and SLE coexist. Most of the diseases occur in RA and the related manifestations of RA are more serious than those of SLE. The incidence of Rhupus syndrome may be related to the change of sex hormone levels.

Objective: To investigate the application value of serum 25-hydroxy vitamin D [25(OH)D] in systemic lupus erythematosus (SLE)., Methods: Data of 158 patients with SLE in Department of Rheumatology and Immunology in the People's Hospital of Xinjiang Uygur Autonomous Region from July 2016 to July 2019. All the SLE patients were divided into two groups by SLE scores of the disease activity index (SLEADI): 59 cases of active group (SLEADI > 4), 99 cases of non-active group (SLEDAI ≤4). Fifty healthy people were selected as healthy control group. The patients' general information and their laboratory data including serum 25(OH)D levels were collected. Statistical methods used were t -test, Spearman's correalation analysis and Logistic regression analysis., Results: (1) A total of 208 cases were included in this study. The level of 25(OH)D in SLE group [10.4(5.6, 15.8) μg/L] was significantly lower than that in healthy control group [25.5(22.8, 32.3) μg/L, P < 0.01]. 25(OH)D level in active SLE patients [6.2(3.7, 13.8) μg/L] was significantly lower than that in remission SLE patients [12.3(7.2, 16.7) μg/L, P < 0.01]. The serum 25(OH)D level in lupus nephritis [6.7 (4.4, 12.9) μg/L] was significantly lower than that in SLE without renal involvement [13.3 (7.4, 18.7) μg/L, P < 0.01]. (2) A significant negative correlation was demonstrated between the serum level of 25(OH)D and SLEDAI ( r =-0.35, P < 0.01), and the 24h urinary protein excretion ( r =-0.39, P < 0.01).Positive correlation was demonstrated between the serum level of 25(OH)D and C3 that decreased ( r =0.249, P < 0.05). (3) Univariate analysis showed anti- dsDNA antibodies(ds-DNA), anti-Sm antibodies(Sm), IgG, C3, C4, erythrocyte sedimentation rate (ESR), 24h urinary protein quantification(24h-pro) and 25(OH)D were associated with disease activity in the SLE patients; Multivariate Logistic regression analysis showed that 25(OH)D was associated with the disease activity of the lupus patients., Conclusion: The decrease of vitamin D level is related to the disease activity of SLE patients, and may be related to lupus nephritis, which plays an important role in the occurrence and development of SLE.

Although non-phthalate plasticizers are widely used in various consumer products as substitutes for phthalates, currently little is known about their environmental occurrence and the risks of human exposure. To characterize the pollution and human exposure risk in indoor environments, house dust samples collected from 83 households in Guangzhou were analyzed for twelve typical non-phthalate plasticizers. Results showed that dioctyl terephthalate (DEHT), trioctyl trimellitate (TOTM), acetyl lemon tributyl ester (ATBC), heptylnonyl adipate, di(2-ethylhexyl) adipate, and trioctyl trimellitate were detected in all samples. The total concentrations of non-phthalate plasticizers ranged from 22.4 to 615 μg ·g -1 with a median of 101 μg ·g -1 . DEHT had the highest concentrations (9-487 μg ·g -1 ), followed by TOTM (0.3-87 μg ·g -1 ) and ATBC (1.7-50 μg ·g -1 ). Daily intakes via dust ingestion for adults and children were estimated based on the dust concentrations. The total daily intake of children was 367 ng ·(kg ·d) -1 , which was 8-9 times higher than that of adults[43 ng ·(kg ·d) -1 ]. Further risk assessment through the hazard quotient approach showed that the exposure of adults and children to non-phthalic plasticizers via dust ingestion was within an acceptable risk range.

Based on the clinical characteristics of atopic dermatitis( AD) in traditional Chinese medicine( TCM) and Western medicine,the existing animal models were analyzed,and the coincidence degree,advantages and disadvantages between the models and the clinical manifestations of AD were evaluated,so as to provide reference for establishing a rational animal model. After consulting relevant literatures in recent years and summarizing the existing modeling methods,it is found that spontaneous,transgenic/gene knockout models were highly consistent,but with high breeding conditions and expensive prices. The hapten-induced model was low in cost and fast in modeling. It revealed the corresponding mechanism of AD to a certain extent,but did not fully reflect the state of the entire process of AD. The modeling method was guided by Western medicine,but with a lack of pathogenic factors of traditional Chinese medicine,and so has certain limitations in TCM research. Therefore,it is necessary to combine the etiology,pathogenesis and clinical mani-festations of AD with traditional Chinese and Western medicine,so as to improve the coincidence degree between the model and the characteristics of clinical symptoms and lay the foundation for in-depth studies on AD.

Optical data are important data sources for operating state estimation of space targets. Inversion of the rotation rate of tumbling targets via light curves can help us perform on-orbit services. However, previous methods cannot estimate the precession and spin rates of tumbling targets from light curves simultaneously. To solve the problem, an efficient precession and spin rate estimation algorithm for tumbling targets is proposed in this paper. The method combines the variational mode decomposition (VMD) method and mutual information (MI). Specifically, VMD is utilized to decompose each light curve into discrete frequency intrinsic mode functions (IMFs). Then, the MI between each IMF and light curve is generated, and the IMF frequencies corresponding to the two maximum MI values are extracted as spin and precession frequencies. Finally, the two frequencies are converted into spin and precession rates. Experimental results show that the estimation accuracy of the precession and spin rates is no less than 97% for a small nutation angle (no greater than 20º). The method provides a simple way to invert a space target state and mine more information from light curves.

Ustilago maydis is a phytopathogenic fungus responsible for corn smut disease. Although it is a very well-established model organism for the study of plant-microbe interactions, its potential to produce specialized metabolites, which might contribute to this interaction, has not been studied in detail. By analyzing the U. maydis genome, we identified a biosynthetic gene cluster whose activation led to the production of a black melanin pigment. Single deletion mutants of the cluster genes revealed that five encoded enzymes are required for the accumulation of the black pigment, including three polyketide synthases ( pks3 , pks4 , and pks5 ), a cytochrome P450 monooxygenase ( cyp4 ), and a protein with similarity to versicolorin B synthase ( vbs1 ). Metabolic profiles of deletion mutants in this gene cluster suggested that Pks3 and Pks4 act in concert as heterodimers to generate orsellinic acid (OA), which is reduced to the corresponding aldehyde by Pks5. The OA-aldehyde can then react with triacetic acid lactone (TAL), also derived from Pks3/Pks4 heterodimers to form larger molecules, including novel coumarin derivatives. Our findings suggest that U. maydis synthesizes a novel type of melanin based on coumarin and pyran-2-one intermediates, while most fungal melanins are derived from 1,8-dihydroxynaphthalene (DHN) or l-3,4-dihydroxyphenylalanine (l-DOPA). Along with these observations, this work also provides insight into the mechanisms of polyketide synthases in this filamentous fungus. IMPORTANCE The fungus Ustilago maydis represents one of the major threats to maize plants since it is responsible for corn smut disease, which generates considerable economical losses around the world. Therefore, contributing to a better understanding of the biochemistry of defense mechanisms used by U. maydis to protect itself against harsh environments, such as the synthesis of melanin, could provide improved biological tools for tackling the problem and protect the crops. In addition, the fact that this fungus synthesizes melanin in an unconventional way, requiring more than one polyketide synthase for producing melanin precursors, gives a different perspective on the complexity of these multidomain enzymes and their evolution in the fungal kingdom., (Copyright © 2021 American Society for Microbiology.)

Objectives: To fully assess the quality of the guidelines for the management of malignant pleural effusions (MPE) and ascites and reveal the heterogeneity of recommendations and possible reasons among guidelines., Methods: A systematic search was performed in the database to obtain guidelines for the management of MPE and ascites. The AGREE IIGtool was used to assess the quality of these guidelines. The Measurement Scale of Rate of Agreement (MSRA) was introduced to assess the scientific agreement of formulated recommendations for the management of MPE and ascites among guidelines, and evidence supporting these recommendations was extracted and analyzed., Results: Nine guidelines were identified. Only 4 guidelines scored more than 60% and are worth recommending. Recommendations were also heterogeneous among guidelines for the management of MPE, and the main reasons were the different emphases of the recommendations for the treatment of MPE, the contradictions in recommendations, and the unreasonably cited evidence for MPE., Conclusions: The quality of the management guidelines for patients with MPE and malignant ascites was highly variable. Specific improvement of the factors leading to the heterogeneity of recommendations will be a reasonable and effective way for developers to upgrade the recommendations in the guidelines for MPE.

Fruiting body-forming members of the Basidiomycota maintain their ecological fitness against various antagonists like ascomycetous mycoparasites. To achieve that, they produce myriads of bioactive compounds, some of which are now being used as agrochemicals or pharmaceutical lead structures. Here, we screened ethyl acetate crude extracts from cultures of thirty-five mushroom species for antifungal bioactivity, for their effect on the ascomycete Saccharomyces cerevisiae and the basidiomycete Ustilago maydis . One extract that inhibited the growth of S. cerevisiae much stronger than that of U. maydis was further analyzed. For bioactive compound identification, we performed bioactivity-guided HPLC/MS fractionation. Fractions showing inhibition against S. cerevisiae but reduced activity against U. maydis were further analyzed. NMR-based structure elucidation from one such fraction revealed the polyyne we named feldin, which displays prominent antifungal bioactivity. Future studies with additional mushroom-derived eukaryotic toxic compounds or antifungals will show whether U. maydis could be used as a suitable host to shortcut an otherwise laborious production of such mushroom compounds, as could recently be shown for heterologous sesquiterpene production in U. maydis .

The novel coronavirus disease (COVID-19) has affected hundreds of millions of people worldwide. Data collection in the ascending phase is crucial to address a rapidly evolving crisis by helping us understand the uncertain relationship between risk communication and psychological responses. Data were collected from 26 January 26, 2020, until February 17, 2020, with a mean test-retest interval of 16 days. A total of 846 adults from four residential communities in high-risk areas (Wuhan city) and low-risk areas (Zhengzhou city) were invited to complete a set of Internet-based questionnaires measuring the adoption of preventive behaviors, appraisal of risk communication, anxiety level, and susceptibility to emotional contagion. At the baseline assessment (Wave 1), 58 withdrew from the study, and 788 (433 females) completed the questionnaires. At the Wave 2 survey, 318 (185 females) adults from Wave 1 were retained. The results from cross-lagged models demonstrated reciprocal negative associations between anxiety and risk communication and between the appraisal of risk communication and the adoption of preventive behaviors. In addition, a higher appraisal of risk communication in the initial period of the outbreak mitigated the respondents' susceptibility to emotional contagion later on. Susceptibility to emotional contagion was positively associated with preventive behaviors taken. Furthermore, multiple-group structural equation modeling suggested that risk communication was more likely to affect the susceptibility to emotional contagion of people on the frontline of the outbreak than people living in low-risk areas. This study demonstrated the importance of risk communication aimed at encouraging appropriate countermeasures against virus outbreaks., (Copyright © 2020 Jin, Zhao, Xia, Chen, Yu, Tamunang Tamutana, Yuan, Shi, Adamseged, Kogay and Park.)

Objectives: Due to recent developments and the wide application of percutaneous transforaminal discectomy (PTED) in China, we herein compare its clinical effects with microendoscopic discectomy (MED) for the treatment of lumbar disc herniation in terms of recurrence and revision rates., Methods: Six databases, namely, PubMed, EMBASE, Cochrane Library, Ovid, China National Knowledge Infrastructure and Wanfang, were searched by computer. The literature was screened according to inclusion and exclusion criteria, and the quality of the included literature was evaluated. After extracting the data from the papers, Review Manager 5.2 software (Cochrane Collaboration, Oxford, UK) was applied to analyze these data. Finally, sensitivity and publication bias analyses of the results were conducted., Results: A total of 12 studies consisting of 2400 patients were included in this meta-analysis. A comparison of PTED with MED revealed higher postoperative recurrence and postoperative revision rates for PTED (odds ratio [OR] recurrence, 1.60; 95% confidence interval [CI], 1.01 to 2.53; p=0.05 and OR revision, 1.77; 95% CI, 1.18 to 2.64, p=0.006)., Conclusion: PTED has a number of advantages because it is a minimally invasive surgery, but its recurrence and revision rates are higher than MED. Therefore, MED should not be completely replaced by PTED.

Aims: Both amnestic mild cognitive impairment (aMCI) and remitted late-onset depression (rLOD) confer a high risk of developing Alzheimer's disease (AD). This study aims to determine whether the Characterizing AD Risk Events (CARE) index model can effectively predict conversion in individuals at high risk for AD development either in an independent aMCI population or in an rLOD population., Methods: The CARE index model was constructed based on the event-based probabilistic framework fusion of AD biomarkers to differentiate individuals progressing to AD from cognitively stable individuals in the aMCI population (27 stable subjects, 6 progressive subjects) and rLOD population (29 stable subjects, 10 progressive subjects) during the follow-up period., Results: AD diagnoses were predicted in the aMCI population with a balanced accuracy of 80.6%, a sensitivity of 83.3%, and a specificity of 77.8%. They were also predicted in the rLOD population with a balanced accuracy of 74.5%, a sensitivity of 80.0%, and a specificity of 69.0%. In addition, the CARE index scores were observed to be negatively correlated with the composite Z scores for episodic memory (R 2  = .17, P < .001) at baseline in the combined high-risk population (N = 72)., Conclusions: The CARE index model can be used for the prediction of conversion to AD in both aMCI and rLOD populations effectively. Additionally, it can be used to monitor the disease severity of patients., (© 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Besides generating vision, light modulates various physiological functions, including mood. While light therapy applied in the daytime is known to have anti-depressive properties, excessive light exposure at night has been reportedly associated with depressive symptoms. The neural mechanisms underlying this day-night difference in the effects of light are unknown. Using a light-at-night (LAN) paradigm in mice, we showed that LAN induced depressive-like behaviors without disturbing the circadian rhythm. This effect was mediated by a neural pathway from retinal melanopsin-expressing ganglion cells to the dorsal perihabenular nucleus (dpHb) to the nucleus accumbens (NAc). Importantly, the dpHb was gated by the circadian rhythm, being more excitable at night than during the day. This indicates that the ipRGC→dpHb→NAc pathway preferentially conducts light signals at night, thereby mediating LAN-induced depressive-like behaviors. These findings may be relevant when considering the mental health effects of the prevalent nighttime illumination in the industrial world.