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Background: Radioresistance is a key clinical constraint on the efficacy of radiotherapy in lung cancer patients. REV1 DNA directed polymerase (REV1) plays an important role in repairing DNA damage and maintaining genomic stability. However, its role in the resistance to radiotherapy in lung cancer is not clear. This study aims to clarify the role of REV1 in lung cancer radioresistance, identify the intrinsic mechanisms involved, and provide a theoretical basis for the clinical translation of this new target for lung cancer treatment., Methods: The effect of targeting REV1 on the radiosensitivity was verified by in vivo and in vitro experiments. RNA sequencing (RNA-seq) combined with nontargeted metabolomics analysis was used to explore the downstream targets of REV1. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify the content of specific amino acids. The coimmunoprecipitation (co-IP) and GST pull-down assays were used to validate the interaction between proteins. A ubiquitination library screening system was constructed to investigate the regulatory proteins upstream of REV1., Results: Targeting REV1 could enhance the radiosensitivity in vivo, while this effect was not obvious in vitro. RNA sequencing combined with nontargeted metabolomics revealed that the difference result was related to metabolism, and that the expression of glycine, serine, and threonine (Gly/Ser/Thr) metabolism signaling pathways was downregulated following REV1 knockdown. LC-MS/MS demonstrated that REV1 knockdown results in reduced levels of these three amino acids and that cystathionine γ-lyase (CTH) was the key to its function. REV1 enhances the interaction of CTH with the E3 ubiquitin ligase Rad18 and promotes ubiquitination degradation of CTH by Rad18. Screening of the ubiquitination compound library revealed that the ubiquitin-specific peptidase 9 X-linked (USP9X) is the upstream regulatory protein of REV1 by the ubiquitin-proteasome system, which remodels the intracellular Gly/Ser/Thr metabolism., Conclusion: USP9X mediates the deubiquitination of REV1, and aberrantly expressed REV1 acts as a scaffolding protein to assist Rad18 in interacting with CTH, promoting the ubiquitination and degradation of CTH and inducing remodeling of the Gly/Ser/Thr metabolism, which leads to radioresistance. A novel inhibitor of REV1, JH-RE-06, was shown to enhance lung cancer cell radiosensitivity, with good prospects for clinical translation., (© 2024. The Author(s).)

Polyfunctionalized arenes are privileged structural motifs in both academic and industrial chemistry. Conventional methods for accessing this class of chemicals usually involve stepwise modification of phenyl rings, often necessitating expensive noble metal catalysts and suffering from low reactivity and selectivity when introducing multiple functionalities. We herein report dehydrogenative synthesis of N -functionalized 2-aminophenols from cyclohexanones and amines. The developed reaction system enables incorporating amino and hydroxyl groups into aromatic rings in a one-shot fashion, which simplifies polyfunctionalized 2-aminophenol synthesis by circumventing issues associated with traditional arene modifications. The wide substrate scope and excellent functional group tolerance are exemplified by late-stage modification of complex natural products and pharmaceuticals that are unattainable by existing methods. This dehydrogenative protocol benefits from using 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) as oxidant that offers interesting chemo- and regio-selective oxidation processes. More notably, the essential role of in situ generated water is disclosed, which protects aliphatic amine moieties from overoxidation via hydrogen bond-enabled interaction.

MicroRNAs have been studied extensively in neurodegenerative diseases. In a previous study, miR-153 promoted neural differentiation and projection formation in mouse hippocampal HT-22 cells. However, the pathways and molecular mechanism underlying miR-153 - induced neural differentiation remain unclear. To explore the molecular mechanism of miR-153 on neural differentiation, we performed RNA sequencing on miR-153-overexpressed HT-22 cells. Based on RNA sequencing, differentially expressed genes (DEGs) and pathways in miR-153-overexpressed cells were identified. The Database for Annotation, Visualization and Integrated Discovery and Gene Set Enrichment Analysis were used to perform functional annotation and enrichment analysis of DEGs. Targetscan predicted the targets of miR-153. The Search Tool for the Retrieval of Interacting Genes and Cytoscape, were used to construct protein-protein interaction networks and identify hub genes. Q-PCR was used to detect mRNA expression of the identified genes. The expression profiles of the identified genes were compared between embryonic days 9.5 (E9.5) and E11.5 in the embryotic mouse brain of the GDS3442 dataset. Cell Counting Kit-8 assay was used to determine cell proliferation and cellular susceptibility to amyloid β-protein (Aβ) toxicity in miR-153-overexpressed cells. The results indicated that miR-153 increased cell adhesion/Ca 2+ (Cdh5, Nrcam, and P2rx4) and Bdnf/Ntrk2 neurotrophic signaling pathway, and decreased ion channel activity (Kcnc3, Kcna4, Clcn5, and Scn5a). The changes in the expression of the identified genes in miR-153-overexpressed cells were consistent with the expression profile of GDS3442 during neural differentiation. In addition, miR-153 overexpression decreased cellular susceptibility to Aβ toxicity in HT-22 cells. In conclusion, miR-153 overexpression may promote neural differentiation by inducing cell adhesion and the Bdnf/Ntrk2 pathway, and regulating electrophysiological maturity by targeting ion channels. MiR-153 may play an important role in neural differentiation; the findings provide a useful therapeutic direction for neurodegenerative diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Catalytic cascade transformations of simple starting materials into highly functionalized molecules bearing a stereochemically defined multisubstituted alkene, which are important in medicinal chemistry, natural product synthesis, and material science, are in high demand for organic synthesis. The development of multiple reaction pathways accurately controlled by catalysts derived from different ligands is a critical goal in the field of catalysis. Here we report a cobalt-catalyzed strategy for the direct coupling of inexpensive 1,3-enynes with two molecules of acrylates to construct a high diversity of functionalized 1,3-dienes containing a trisubstituted or tetrasubstituted olefin. Such cascade reactions can proceed through three different pathways initiated by oxidative cyclization to achieve multiple bond formation in high chemo-, regio- and stereoselectivity precisely controlled by ligands, providing a platform for the development of tandem carbon-carbon bond-forming reactions., (© 2024. The Author(s).)

Aims: This study aims to comprehensively explore the decision-making requirements of women contemplating vaginal birth after cesarean (VBAC)., Design & Methods: A meta-synthesis approach was employed for this study. Using an integrative methodology, we conducted a systematic assessment of women's experiences and needs related to VBAC decision-making. A comprehensive search was conducted across The Cochrane Library, PubMed, EMBASE, Ovid Medline, SCOPUS, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and Wan Fang databases to identify pertinent studies between 2000 and 2022. Furthermore, the reference lists of the included studies were thoroughly examined., Results: Fifteen studies were incorporated, from which seven themes emerged: emotional changes, preference for vaginal birth, unmet information needs, influences on decision-making, decision-making autonomy, aligning information provision with decision-support needs, and the requirement for support systems. Two primary syntheses were constructed on the decision-making process and the need for decision-making aids, respectively., Conclusion: Women opting for VBAC experienced emotional shifts during their decision-making process in pregnancy. There remains a need for an enhanced decision-making tool to guide them in their choice. Recommendations for implementation in VBAC decision aids include facilitating women's involvement in decision-making, satisfying their information needs, and delivering appropriate emotional support., (© 2023 Wiley Periodicals LLC.)

Introduction: Bone defects remain a thorny challenge that clinicians have to face. At present, scaffolds prepared by 3D printing are increasingly used in the field of bone tissue repair. Polylactic acid (PLA) has good thermoplasticity, processability, biocompatibility, and biodegradability, but the PLA is brittle and has poor osteogenic performance. Beta-tricalcium phosphate (β-TCP) has good mechanical properties and osteogenic induction properties, which can make up for the drawbacks of PLA. Methods: In this study, photocurable biodegradable polylactic acid (bio-PLA) was utilized as the raw material to prepare PLA/β-TCP slurries with varying β-TCP contents (β-TCP dosage at 0%, 10%, 20%, 30%, 35% of the PLA dosage, respectively). The PLA/β-TCP scaffolds were fabricated using liquid crystal display (LCD) light-curing 3D printing technology. The characterization of the scaffolds was assessed, and the biological activity of the scaffold with the optimal compressive strength was evaluated. The biocompatibility of the scaffold was assessed through CCK-8 assays, hemocompatibility assay and live-dead staining experiments. The osteogenic differentiation capacity of the scaffold on MC3T3-E1 cells was evaluated through alizarin red staining, alkaline phosphatase (ALP) detection, immunofluorescence experiments, and RT-qPCR assays. Results: The prepared scaffold possesses a three-dimensional network structure, and with an increase in the quantity of β-TCP, more β-TCP particles adhere to the scaffold surface. The compressive strength of PLA/β-TCP scaffolds exhibits a trend of initial increase followed by decrease with an increasing amount of β-TCP, reaching a maximum value of 52.1 MPa at a 10% β-TCP content. Degradation rate curve results indicate that with the passage of time, the degradation rate of the scaffold gradually increases, and the pH of the scaffold during degradation shows an alkaline tendency. Additionally, Live/dead staining and blood compatibility experiments suggest that the prepared PLA/β-TCP scaffold demonstrates excellent biocompatibility. CCK-8 experiments indicate that the PLA/β-TCP group promotes cell proliferation, and the prepared PLA/β-TCP scaffold exhibits a significant ability to enhance the osteogenic differentiation of MC3T3-E1 cells in vitro . Discussion: 3D printed LCD photocuring PLA/β-TCP scaffolds could improve surface bioactivity and lead to better osteogenesis, which may provide a unique strategy for developing bioactive implants in orthopedic applications., Competing Interests: 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., (Copyright © 2024 Wang, Ye, Chen, Zhang, Zeng, Liu, Tan and Jie.)

Asthma is a common chronic heterogeneous disease. Outdoor air pollutants are an important cause of acute asthma. Until now, the association between the risk of acute asthma and outdoor air pollutants is unclear. And the relationship between the different phenotypes of asthma and outdoor air pollutants has not been reported. Thus, an analysis of the association between outdoor air pollutants and daily acute asthma inpatient and outpatient visits in Xi'an, China, from January 1 to December 31, 2018, was conducted. A total of 3395 people were included in the study. The statistical analysis and relational analysis based on the logistic regression were used for illustrating the relatedness of the acute asthma risk factor and phenotype with outdoor air pollutants, while the age, gender, pollen peak and non-pollen peak periods, high type 2 (T2) asthma and non-high T2 asthma were also stratified. Results showed that particulate matter with particle size below 10 μm and 2.5 μm (PM 10 and PM 2.5 ), sulfur dioxide(SO 2 ), nitrogen dioxide(NO 2 ), and carbon monoxide(CO) increase the risk of acute asthma and that air pollutants have a lagged effect on asthma patients. PM 10 , NO 2 , CO, and Ozone (O 3 ) are associated with an increased risk of acute attacks of high T2 asthma. PM 10 , PM 2.5 , SO 2 , NO 2 and CO are associated with an increased risk of acute asthma in males of 0-16 years old. PM 10 and PM 2.5 are more harmful to asthma patients with abnormal lung function., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Ethnopharmacological Relevance: Astragalus polysaccharide (APS), the most biologically active ingredient of Astragali Radix, is used to treat diabetes mellitus (DM)-related chronic wounds in traditional Chinese medicine for several decades. This herb possesses an anti-inflammatory effect. Our study proved that APS can reduce excessive inflammation at the late phase of wound-healing in diabetic ulcers., Aim of the Study: To clarify the molecular mechanism of APS in promoting wound-healing via reducing excessive inflammation in diabetic ulcers during the late stages of wound-healing., Methods and Materials: The rat model of the diabetic ulcers was established via intraperitoneal injection of streptozocin (60 mg/kg). We detected the regulation of APS on diabetic ulcers by measuring wound-healing rates. Bioinformatics was used to predict the target genes of APS, and autodocking was used to predict the combination of APS and target genes. Immunohistochemistry, Enzyme-linked immunosorbent assay, Western blot, immunofluorescence staining, flow cytometry, and flow cytometric sorting were investigated., Results: The results demonstrated that APS promoted wound-healing and inhibited excessive inflammation at the late phase of wound-healing in diabetic rats. Mechanistic findings showed that APS promoted the expression of β-catenin and Rspo3 while inhibiting the expression of NF-KB and GSK-3β, which leads to the transformation of M1-type macrophages into M2-type macrophages and thus reducing excessive inflammation at the late phase of wound-healing in diabetic ulcers., Conclusion: We found an interesting finding that APS promoted the polarization of macrophages towards M2-type through the β-catenin/NF-κB axis to reduce excessive inflammation at the late phase of wound-healing. Therefore, APS may be a promising drug for treating diabetic ulcers in clinic., Competing Interests: All authors declare no conflict of interest., (© 2024 The Authors.)

Taraxacum kok-saghyz (TKS) latex is a natural latex produced from its root, and its extraction optimization process is mainly studied in the present paper. The composition of fresh roots of TKS was quantitatively analyzed, and the results showed that the moisture content of the fresh root was approximately 70 %, and the rubber content averaged to 6 % (dry weight ratio). An optimal process route for extracting the TKS latex was finally determined, making the extraction efficiency reach about 80 %, and a new latex extraction process was established and optimized and named "the process of Buffer Extraction TKS Latex (BETL)". Hevea latex, extracted TKS latex and TKS latex collected directly from the broken roots were compared for study. The results showed that, like Hevea latex, the appearance of TKS latex was milky white; and after centrifugation, both showed four layers from top to bottom: rubber particles, Frey-Wyssling particles, C-serum and lutoids. The results of the composition analysis showed that the concentration of TKS latex ranged from 54.54 % to 68.25 %, which is close to that of concentrated Hevea latex; the moisture content of TKS latex was between 31.75 % and 45.46 %. The protein content of TKS latex was 13.51 mg/mL, which was lower than that of Hevea latex at the same rubber hydrocarbon concentration. The molecular structures and properties of Hevea latex, the extracted TKS latex, and the collected TKS latex were characterized by FTIR, 13 C NMR, GPC, TG, SEM and LPSA, and the results showed that the main components and structure of the three latexes were similar, which are all cis -1,4-polyisoprene, and include the proteins and lipids. The distributions molecular weights of the three latexes all showed a bimodal distribution, but the molecular weight of the latex collected from TKS was lower, which indicates the larger molecules were difficult to flow outside the root automatically. The Hevea latex and TKS latex rubber particles were both core-shell structure and the size distribution were bimodal, which was consistent with the GPC analysis results., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Radioresistance is a major constraint on the efficacy of lung cancer radiotherapy, but its mechanism has not been fully elucidated. Here, we found that FBXO22 was aberrantly highly expressed in lung cancer and that FBXO22 knockdown increased the radiosensitivity of lung cancer cells. Mechanistically, FBXO22 promoted Rad51 gene transcription by increasing the level of FOXM1 at the Rad51 promoter, thereby inducing the formation of lung cancer radioresistance. Furthermore, we found that deguelin, a potential inhibitor of FBXO22, enhanced radiosensitivity in an FBXO22/Rad51-dependent manner and was safely tolerated in vivo. Collectively, our results illustrate that FBXO22 induces lung cancer radioresistance by activating the FOXM1/Rad51 axis and provide preclinical evidence for the clinical translation of this critical target., (© 2024. The Author(s).)

To overcome the defects of Citrus aurantium L. var. amara Engl. essential oil (CAEO), such as high volatility and poor stability, supercritical fluid-extracted CAEO nanoemulsion (SFE-CAEO-NE) was prepared by the microemulsification method. Emulsifiers comprising Tween 80, polyoxyethylenated castor oil (EL-40), and 1,2-hexanediol, and an oil phase containing SFE-CAEO were used for microemulsification. We examined the physicochemical properties of SFE-CAEO-NE and steam distillation-extracted CAEO nanoemulsion (SDE-CAEO-NE), which were prepared using different concentrations of the emulsifiers. The mean particle size and zeta potential were 21.52 nm and -9.82 mV, respectively, for SFE-CAEO-NE, and 30.58 nm and -6.28 mV, respectively, for SDE-CAEO-NE, at an emulsifier concentration of 15% (w/w). SFE-CAEO-NE displayed better physicochemical properties compared with SDE-CAEO-NE. Moreover, its physicochemical properties were generally stable at different temperatures (-20-60℃), pH (3-8), and ionic strengths (0-400 mM). No obvious variations in particle size, zeta potential, and Ke were observed after storing this nanoemulsion for 30 days at 4℃, 25℃, and 40℃, suggesting that it had good stability. The sleep-promoting effect of SFE-CAEO-NE was evaluated using a mouse model of insomnia. The results of behavioral tests indicated that SFE-CAEO-NE ameliorated insomnia-like behavior. Moreover, SFE-CAEO- NE administration increased the serum concentrations of neurotransmitters such as 5-hydroxytryptamine and γ-aminobutyric acid, and decreased that of noradrenaline in mice. It also exerted a reparative effect on the function of damaged neurons. Overall, SFE-CAEO-NE displayed a good sleep-promoting effect.

Objective: To analyze the effects of different types of inhalant allergens on the lung functions of adult patients with bronchial asthma., Methods: This cross-sectional study included a total of 47 adults diagnosed with bronchial asthma at the Respiratory Outpatient Department of Tianjin First Central Hospital. Patients were divided into non-sensitized and sensitized groups based on the number of positive allergens detected and classified into four groups (the dust mite mixed group, animal dander mixed group, pollen-mixed group, and mold mixed group) based on the type of positive allergen detected. They were tested for the serum concentration of allergen-specific immunoglobulin E (sIgE) using a fluorescence immunoassay analyzer, and lung function was assessed using a pulmonary function testing machine. One-way analysis of variance was used to compare normally distributed data, while the rank sum test was utilized for non-normally distributed data., Results: There was no statistically significant difference in lung function indicators between these two groups (p > .05). There were statistically significant differences in forced expiratory volume in one second as a percentage of the predicted value (FEV 1 %pred) (p = .028), FEV 1 /forced vital capacity as a percentage of the predicted value; (FVC%pred) (p = .016), peak expiratory flow as a percentage of the predicted value (PEF%pred) (p = .001), forced expiratory flow at 50% of the predicted value of forced vital capacity (FEF50%pred) (p = .003), forced expiratory flow at 75% of the predicted value of forced vital capacity (FEF75%pred) (p = .023), and maximal midexpiratory flow (MM)EF75/25%pred (p = .002) among the four groups. The pollen-mixed group had higher PEF%pred (pollen vs. animal dander, p = .067; pollen vs. dust-mites, p = .008; pollen vs. molds, p = .001) and MMEF75/25%pred (pollen vs. animal dander, p = .048; pollen vs. dust-mites, p = .003; pollen vs. molds, p = .001) than the other three groups. The pollen-mixed group had higher FEF50%pred than the dust-mites mixed group (p = .008) and molds-mixed group (p = .001). The pollen-mixed group had higher FEF75%pred (p = .005), FEV 1 %pred (p = .001), and FEV 1 /FVC%pred (p = .001) than the molds-mixed group., Conclusion: Different inhalant allergens had different effects on lung functions in adults with asthma., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Dry eye disease is common among patients with primary Sjögren's syndrome (pSS). Hydroxychloroquine (HCQ), known for its immunomodulatory effects and minimal adverse effects, has emerged as a pivotal treatment option for pSS. Nonetheless, conflicting evidence exists regarding the therapeutic efficacy of HCQ in managing dry eye disease associated with pSS., Objectives: To evaluate the safety and efficacy of oral hydroxychloroquine in treating dry eye disease associated with pSS., Methods: A prospective randomized controlled study was conducted, enrolling pSS patients with moderate to severe dry eye disease. Participants were randomly assigned to an oral HCQ group and an observation group. Various scales (ESSDAI, ESSPRI, OSDI, and SPEED questionnaire score), dry eye-related tests (OSS score, TBUT, and Schirmer test I), ophthalmology-specific tests (BCVA, SD-OCT RT, field of view, latency and amplitudes for multifocal ERG ring 1 and ring 2), whole body protein levels (serum IgA, IgG, and IgM), and blood glucose were assessed before and after 12 months of treatment., Results: Pairwise comparison of the observed indicator baseline revealed no statistical significance (P > .05). After 12 months, the HCQ group exhibited notable improvements in ESSPRI, serum IgA, and Schirmer test I results compared to the control group (P < .05). Both groups demonstrated significant improvements in BCVA, OSDI, SPEED scores, and dry eye-associated examinations compared to baseline (P < .05). Serum IgG and IgM levels decreased in the HCQ group after 12 months of treatment, but without statistical significance (P > .05). None cases of HCQ retinopathy were reported during follow-up., Conclusions: Oral HCQ was demonstrated safety and efficacy in managing pSS-related dry eye disease. Treatment with Oral HCQ markedly reduced the ESSPRI score, improve patients' systemic dryness symptoms, and greatly decreased blood IgA levels. Combined with topical cyclosporin, HCQ improved Schirmer test I scores and alleviated ocular surface inflammation and dry eye signs and symptoms.

Reduction-sulfurization smelting is an effective method for treating solid hazardous waste and recovering valuable components from them. In this work, a waste hydrogenation catalyst (WHC), an automotive exhaust purifier waste catalyst (AEPWC), a vulcanizer, and laterite nickel ore were mixed, and the reduction smelting behavior of this solid waste was investigated. XRD (X-ray diffractometry), TG-DSC (thermogravimetric/differential scanning calorimetry), SEM-EDS (scanning electron microscopy-energy dispersive spectroscopy), OM (optical microscopy), and ICP-OES (inductively coupled plasma-optical emission spectrometry) methods were used to examine the chemical composition, thermal stability, structure, and morphology, as well as the metal content of the samples. Under the Al 2 O 3 -FeO-SiO 2 ternary slag system, at a smelting temperature of 1450 °C, smelting time of 2 h, mass ratio of coke, pyrite, and CaO to waste catalysts of 16, 25, and 0%, respectively, nickel (Ni) and molybdenum (Mo) recovery reached 91.1 and 92.9%, respectively, where average PGMs (platinum group metals, platinum (Pt), palladium (Pd), rhodium (Rh)) recovery reached 96%, although vanadium (V) recovery was only 25.1%. The characterization of the slag shows that Al, Si, and Fe are mainly bound in the form of chemical compounds, while V is intercalated with ferro- or aluminosilicate, which hinders the reduction and sulfurization of V. A series of tests using reduction smelting without sulfurization were also conducted, after which the Ni, Mo, and V recovery reached 96.8, 96.6, and 89.7%, respectively, while PGMs (Pt, Pd, Rh) recovery ranges from 90.2 to 98.0%. The collaborative disposal of primary ore and multisource solid waste has been achieved through two process paths: reducing smelting and reducing sulfurization smelting, which provide reference for the collaborative smelting of multisource secondary resources., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

To explore the signal transmission mechanism of the arbuscular mycorrhizal network against root rot of Salvia miltiorrhiza. In this experiment, the arbuscular mycorrhizal hyphal network was established among Salvia miltiorrhiza plants, and a two plant three-compartment culture model was established. The root of the donor Salvia miltiorrhiza was inoculated with the pathogenic fungi Fusarium solani. The changes of hormone signals such as jasmonic acid and salicylic acid and the expression of related defense genes in the recipient Salvia miltiorrhiza plants in different periods were measured, to study the underground disease resistance signal transmission mechanism among medicinal plants. Salvia miltiorrhiza can transmit the signal of resistance to root rot through the jasmonic acid pathway; When plants suffer from disease stress, the content of JA increases significantly, and the increase of JA content will inhibit the content of SA in plants; The gene expression of PR-10 gene in the roots of Salvia miltiorrhiza with arbuscular mycorrhizal network infected by pathogenic fungi was 17.56 times higher than that inoculated only with pathogenic fungi; Changes in hormone content will also cause changes in the expression of related defense genes, such as SnRK2 is inhibited by ABA in the signal transduction pathway, while JA and ABA show antagonistic changes after inoculation of pathogenic fungi in Salvia miltiorrhiza, so JA may positively regulate the expression of SnRK2 gene. Plants can transmit signals through AM hyphal network after being stressed by the pathogen Fusarium solani. In the arbuscular mycorrhizal hyphal network, JA has important significance for the signal transmission of resistance to root rot and disease resistance of Salvia miltiorrhiza, which can make Salvia miltiorrhiza ready for stress resistance and improve the stress resistance of Salvia miltiorrhiza. This experiment is of great significance to further analyze the signal transmission mechanism of the arbuscular mycorrhizal hyphal network., (© 2023. Springer Nature Limited.)

In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All mothers (n = 30) had AChR antibodies and, when tested, binding to fAChR was often much greater than that to the adult AChR isoform. Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%), or during early infancy, mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/intravenous immunoglobulin/plasmapheresis) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P < 0.05) and other complications, with treatment approaches involving intravenous immunoglobulin/ plasmapheresis administered early in pregnancy most effective. We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognized and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose 'fetal acetylcholine receptor antibody-related disorders' (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognize, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: The pan-immune-inflammation value (PIV) has been reported as a promising prognostic biomarker in multiple cancers but still remains inconclusive. The objective of this study is to systematically investigate the association of the pretreatment PIV with survival outcomes in cancer patients, based on available literature., Methods: Online databases including PubMed, Embase and the Web of Science were thoroughly searched for studies evaluating the prognostic role of the pretreatment PIV in cancers from the inception to June 2023. Hazard ratios (HRs) with 95% confidence intervals (CIs) were always assessed using a random-effects model. Statistical analyses were performed using Stata 12.0., Results: Thirty studies were finally included after comprehensively study searching. In total, 8,799 cancer patients were enrolled in this meta-analysis. The pooled results demonstrated that patients in the high PIV group had a significantly poorer overall survival (HR = 2.07; 95%CI: 1.77-2.41; I 2 = 73.0%) and progression-free survival (HR = 1.83; 95%CI: 1.37-2.45; I 2 = 98.2%) than patients in the low PIV group. The prognostic significance of the PIV score on overall survival and progression-free survival was observed across various geographical regions, tumor stages and treatment strategies. Sensitivity analyses supported the stability of the above combined results., Conclusion: This meta-analysis demonstrated that the pretreatment PIV could be a non-invasive and efficacious prognostic biomarker for cancer patients., Competing Interests: 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., (Copyright © 2023 Hai-Jing, Shan and Jie-Qiong.)

Summary: Autologous fat injection is one of the most popular methods for the treatment of temporal depression; however, accurate puncture into the target layer without vascular compromise is hard to achieve. With the aid of high-frequency ultrasonography, the authors performed autologous fat transplantation after visualization in five cases, with satisfactory results. The authors observed the course of superficial temporal vessels, the orbitozygomatic artery, and sentinel veins preoperatively, and used high-frequency ultrasonography to guide lipotransfer into the desired layer intraoperatively, to avoid intravascular injection. With the aid of high-frequency ultrasonography, the authors can easily prevent vascular complications and personalize surgical procedures, as anatomical variations of vasculature can also be detected by means of this method., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Due to the large specific surface area and rich pore structure, chitosan nanofiber membrane has many advantages over conventional gel-like or film-like products. However, the poor stability in acidic solutions and relatively weak antibacterial activity against Gram-negative bacteria severely restrict its use in many industries. Here, we present a chitosan-urushiol composite nanofiber membrane prepared by electrospinning. Chemical and morphology characterization revealed that the formation of chitosan-urushiol composite involved the Schiff base reaction between catechol and amine groups and the self-polymerization of urushiol. The unique crosslinked structure and multiple antibacterial mechanisms endowed the chitosan-urushiol membrane with outstanding acid resistance and antibacterial performance. After immersion in HCl solution at pH 1, the membrane maintained its intact appearance and satisfactory mechanical strength. In addition to its good antibacterial performance against Gram-positive Staphylococcus aureus (S. aureus), the chitosan-urushiol membrane exhibited synergistic antibacterial activity against Gram-negative Escherichia coli (E. coli) that far exceeded that of neat chitosan membrane and urushiol. Moreover, cytotoxicity and hemolysis assays revealed that the composite membrane had good biocompatibility similar to that of neat chitosan. In short, this work provides a convenient, safe, and environmentally friendly method to simultaneously enhance the acid resistance and broad-spectrum antibacterial activity of chitosan nanofiber membranes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The changes in the expression of genes related to digestion and metabolism may be various in different dietary mammals from juvenile to adult, especially, the giant panda ( Ailuropoda melanoleuca ) and red panda ( Ailurus fulgens ), which were once carnivores but have shifted to being specialized bamboo eaters, are unique features of their changes are more unclear. To elucidate the changing patterns of gene expression related to digestion and metabolism from juvenile to adult in different dietary mammals, we performed transcriptome analysis of the liver or pancreas in giant and red pandas, herbivorous rabbits ( Oryctolagus cuniculus ) and macaques ( Macaca mulatta ), carnivorous ferrets ( Mustela putorius furo ), and omnivorous mice ( Mus musculus ) from juvenile to adult. During the transition from juvenile to adulthood, giant and red pandas, as well as rabbits and macaques, show significant upregulation of key genes for carbohydrate metabolism, such as starch hydrolysis and sucrose metabolism, and unsaturated fatty acid metabolism, such as linoleic acid, while there is no significant difference in the expression of key genes for fatty acid β-oxidation. A large number of amino acid metabolism related genes were upregulated in adult rabbits and macaques compared to juveniles. While adult giant and red pandas mainly showed upregulation of key genes for arginine synthesis and downregulation of key genes for arginine and lysine degradation. In adult stages, mouse had significantly higher expression patterns in key genes for starch hydrolysis and sucrose metabolism, as well as lipid and protein metabolism. In contrast to general expectations, genes related to lipid, amino acid and protein metabolism were significantly higher expressed in adult group of ferrets, which may be related to their high metabolic levels. Our study elucidates the pattern of changes in the expression of genes related to digestion and metabolism from juvenile to adult in different dietary mammals, with giant and red pandas showing adaptations associated with specific nutritional limitations of bamboo., Competing Interests: 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., (Copyright © 2023 Yizhen, Chen, Jie, Shen, Zhang, Hou, Li, Yan, Zhang and Yang.)

Background: Dendrobium nobile and Dendrobium chrysotoxum are important species of the genus Dendrobium and have great economic and medicinal value. However, the medicinal properties of these two plants remain poorly understood. This study aimed to investigate the medical properties of D. nobile and D. chrysotoxum by conducting a comprehensive chemical profiling of the two plants. Additionally, active compounds and predictive targets for anti-hepatoma activity in D. chrysotoxum extracts were identified using Network Pharmacology., Results: Chemical profiling showed that altogether 65 phytochemicals were identified from D. nobile and D. chrysotoxum, with major classes as alkaloids, terpenoids, flavonoids, bibenzyls and phenanthrenes. About 18 compounds were identified as the important differential metabolites in D. nobile and D. chrysotoxum. Furtherly, CCK-8 results showed that the extracts of stems and leaves of D. nobile and D. chrysotoxum could inhibit the growth of Huh-7 cells, and the anti-hepatoma activity of extracts were dose-dependent. Among the extracts, the extract of D. chrysotoxum showed significant anti-hepatoma activity. In order to find the potential mechanism of anti-hepatoma activity of D. chrysotoxum, five key compounds and nine key targets were obtained through constructing and analyzing the compound-target-pathway network. The five key compounds were chrysotobibenzyl, chrysotoxin, moscatilin, gigantol and chrysotoxene. Nine key targets, including GAPDH, EGFR, ESR1, HRAS, SRC, CCND1, HIF1A, ERBB2 and MTOR, could be considered as the core targets of the anti-hepatoma activity of D. chrysotoxum., Conclusions: In this study, the chemical composition difference and anti-hepatoma activity of stems and leaves of D. nobile and D. chrysotoxum were compared, and the potential anti-hepatoma mechanism of D. chrysotoxum was revealed in a multi-target and multi-pathway manner., (© 2023. The Author(s).)

Taraxacum kok-saghyz (TKS) rubber is considered the most ideal alternative source of natural rubber (NR). Extracting rubber from TKS with high quality, low cost, and low pollution is the basis of commercial development. The TKS roots were subjected to morphological observation and detailed compositional analysis. Scanning electron microscopy (SEM) images confirm that rubber filaments are physically entangled with plant tissues due to differences in molecular polarity. Compared with the traditional solvent TKS rubber extraction process, a new rubber extraction process developed in this study, namely, the microbial extraction (″ME″) process, is less harmful to the environment and lower in cost. The ″ME″ process is divided into three steps: dilute acid pretreatment process, enzyme degradation process, and fermentation process. After each step is completed, the purity of TKS rubber will gradually increase from 84.8% to 93.8 to 95.5%. The TKS rubber finally obtained fully meets the requirements of the traditional rubber industry, especially the tire industry. Besides, the yield of biofuel ethanol, a by-product of cellulose fermentation, reaches 2.05 g/100 g of TKS roots (dry weight), which can effectively reduce the production cost of TKS rubber. In the rubber extraction process, microorganisms have little effect on the quality of TKS rubber. The results show that the molecular weight and chemical structure of TKS rubber is very close to NR , so the ″ME″ process can be used as a new method for large-scale extraction of TKS rubber., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Bupi Yishen formula (BYF), a traditional Chinese herbal mixture, has demonstrated better effectiveness than Losartan in preserving renal function and preventing composite severe adverse outcomes in patients with advanced chronic kidney disease (CKD) in a recent randomized controlled trial. Prior studies have shown that BYF exerts anti-inflammatory and anti-fibrotic effects in the kidneys of CKD models, but the underlying mechanisms have not been fully elucidated., Purpose: The aim of this study was to investigate the protective effects of BYF administration on profibrotic phenotypic changes in the kidney and to elucidate its fundamental mechanisms of action., Methods: Adenine and 5/6 nephrectomy rat models were administered with two doses of BYF extract (15 or 30 g/kg/d) by intragastric administration, and Losartan treatment was used as a positive control group. The relationship between BYF renoprotection and restoration of fatty acid dysregulation was examined using the two fibrosis models and TGFb1-induced human tubular HK2 cells. Transcriptomic profiles of the fibrotic kidneys obtained from adenine-induced CKD rats were used to identify the key mechanisms that are affected by BYF intervention. Human relevance and clinical implications were established by re-analysis of the microarray databases of CKD patients and immunostaining on human biopsy specimens., Results: BYF effectively prevented kidney histological damage and ameliorated renal malfunction in the adenine rat model of CKD. BYF robustly attenuated the significant increase in profibrotic and proapoptotic markers in fibrotic kidneys of adenine-induced CKD rats. Transcriptomic analyses of the fibrotic kidneys of the adenine rats identified fatty acid metabolism as the key dysregulated pathway affected by BYF prevention. BYF significantly reversed defective fatty acid oxidation (FAO) and the intracellular lipids accumulation in the fibrotic kidneys induced by 5/6 nephrectomy. Furthermore, BYF prevented dysfunctional fatty acid metabolism, which were associated with the significant improvement of TGFb1-induced profibrotic changes in HK2 human proximal tubular cells. Furthermore, analyses of kidney microarray databases and biopsy specimens of CKD patients suggested that FAO defect is common in CKD in humans., Conclusion: Our exploratory study found that BYF may exert protective effects on renal fibrosis by regulating the fatty acid metabolism of renal tubular cells, which may be a key mechanism for preventing kidney fibrosis in CKD., Competing Interests: Declaration of Competing Interest We the undersigned declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere. We confirm that the manuscript has been reviewed and approved by all named authors. We further confirm that all of us participated sufficiently in the work and agree to take public responsibility for its content. We declare that there are no conflicts of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: The specific functions of PPP1R81 has been elucidated in multiple cancers; however, its role in lower-grade glioma (LGG) remains unknown. In this research, we inspected the specific role of PPP1R81 in LGG., Methods: We totally evaluated the expression pattern and prognostic role of PPP1R81 in multitudinous tumors. Subsequently, we systematically examined the connection between PPP1R81 expression and prognosis, clinical characteristics, biological functions, genetic variations, and immunological characteristics in LGG according to the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Altas (CGGA) databases. In vitro experiments were executed to inspect the expression level and specific roles of PPP1R81 in LGG., Results: PPP1R81 was elevated in multiple tumors and was tightly linked to a poor prognosis. LGG with higher expression of PPP1R81 showed poorer prognosis compared with lower expression of PPP1R81. The results of univariate and multivariate Cox regression analyses confirmed that the expression of PPP1R81 was an independent prognostic biomarker of LGG. Immune cell infiltration, immune checkpoint genes (ICPGs), copy number alterations (CNA), and tumor mutation burden (TMB) were also closely associated with PPP1R81 expression in LGG. In vitro experiments demonstrated that PPP1R81 was up-regulated and closely interrelated with cell proliferation and cell cycle in LGG., Conclusion: PPP1R81 was an independent prognostic signature and underlying therapeutic target for patients with LGG., (© 2023 The Author(s).)

In this study, the surface of aluminum powder was uniformly coated with in situ reduced graphene oxide (r-GO) sheets (Al/r-GO). The Ni powder, Al 2 O 3 powder, and Al/r-GO powders were mixed uniformly in a mass ratio of 20:6:4. In situ rGO-reinforced Ni-Al intermetallic composite coatings were successfully prepared using low-pressure cold spraying and subsequent heat treatment. The microstructure and phase of the composite coatings were characterized using X-ray diffraction (XRD), Raman spectroscopy, and scanning electron microscopy (SEM). The high-temperature wear test was conducted at 200 °C, 400 °C, and 600 °C to understand the mechanism. The results indicate that the in situ rGO-reinforced Ni-Al intermetallic composite coatings exhibit a 33.3% lower friction coefficient and 26% lower wear rate in comparison to pure Ni-Al intermetallic coatings, which could be attributed to the generation of an easy-shearing transferred film between the coating and grinding ball.

Objective: Tirzeptide is a novel glucagon-like peptide-1 receptor (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) drug, which shows good efficiency for weight loss. Therefore, we aim to investigate the efficacy and safety of tirzepatide for weight loss in type 2 diabetes mellitus (T2DM) and obesity patients in this meta-analysis study., Methods: Cochrane Library, PubMed, Embase, Clinical Trials, and Web of Science were searched from inception to October 5, 2022. All randomized controlled trials (RCTs) were included. The odds ratio (OR) was calculated using fixed-effects or random-effects models by Review Manager 5.3 software., Results: In total, ten studies (12 reports) involving 9,873 patients were identified. A significant loss body weight in the tirzepatide group versus the placebo by -9.81 kg (95% CI (-12.09, -7.52), GLP-1 RAs by -1.05 kg (95% CI (-1.48, -0.63), and insulin by -1.93 kg (95% CI (-2.81, -1.05), respectively. In sub-analysis, the body weight of patients was significantly reduced in three tirzepatide doses (5 mg, 10 mg, and 15 mg) when compared with those of the placebo/GLP-1 RA/insulin. In terms of safety, the incidence of any adverse events and adverse events leading to study drug discontinuation was higher in the tirzepatide group, but the incidence of serious adverse events and hypoglycaemia was lower. Additionally, the gastrointestinal adverse events (including diarrhea, nausea, vomiting and decreased appetite) of tirzepatide were higher than those of placebo/basal insulin, but similar to GLP-1 RAs., Conclusion: In conclusion, tirzeptide can significantly reduce the weight of T2DM and patient with obesity, and it is a potential therapeutic regimen for weight-loss, but we need to be vigilant about its gastrointestinal reaction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Diacylglycerol kinase α (DGKA) is the first member discovered from the diacylglycerol kinase family, and it has been linked to the progression of various types of tumors. However, it is unclear whether DGKA is linked to the development of lung cancer., Methods: We investigated the levels of DGKA in the lung cancer tissues. Cell growth assay, colony formation assay and EdU assay were used to examine the effects of DGKA-targeted siRNAs/shRNAs/drugs on the proliferation of lung cancer cells in vitro. Xenograft mouse model was used to investigate the role of DGKA inhibitor ritanserin on the proliferation of lung cancer cells in vivo. The downstream target of DGKA in lung tumorigenesis was identified by RNA sequencing., Results: DGKA is upregulated in the lung cancer cells. Functional assays and xenograft mouse model indicated that the proliferation ability of lung cancer cells was impaired after inhibiting DGKA. And cyclin D3(CCND3) is the downstream target of DGKA promoting lung cancer., Conclusions: Our study demonstrated that DGKA promotes lung tumorigenesis by regulating the CCND3 expression and hence it can be considered as a potential molecular biomarker to evaluate the prognosis of lung cancer patients. What's more, we also demonstrated the efficacy of ritanserin as a promising new medication for treating lung cancer., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Chimeric antigen receptor - T (CAR-T) cell therapy has shown remarkable efficacy in patients with relapsed/refractory multiple myeloma (R/R MM). However, a subset of patients still experienced progression or relapse, and the predictors of prognosis are little known. We analyzed the inflammatory markers before CAR-T cell infusion, to clarify their correlation with survival and toxicity., Methods: This study involved 109 R/R MM patients who received CAR-T therapy between June 2017 and July 2021. Inflammatory markers, including ferritin, c-reactive protein (CRP), and interleukin-6 (IL-6) before CAR-T cell infusion were detected and then categorized by quartiles. Adverse events and clinical outcomes were compared between patients with upper quartile of inflammatory markers and patients with lower three quartiles of inflammatory markers. An inflammatory prognostic index (InPI) based on these three inflammatory markers was developed in this study. Patients were divided into 3 groups according to the InPI score, progression-free survival (PFS) and overall survival (OS) were compared among the groups. In addition, we explored the correlation between cytokine release syndrome (CRS) and pre-infusion inflammatory markers., Results: We found that the pre-infusion high ferritin (hazard ratio [HR], 3.382; 95% confidence interval [CI], 1.667 to 6.863; P = .0007), high CRP (HR, 2.043; 95% CI, 1.019 to 4.097; P = .044), and high IL-6 (HR, 3.298; 95% CI, 1.598 to 6.808; P = .0013) were significantly associated with inferior OS. The formula of the InPI score was based on the HR value of these 3 variables. Three risk groups were formed: (good, 0 to 0.5 point; intermediate, 1 to 1.5 points; poor, 2 to 2.5 points). Median OS for patients with good, intermediate, and poor InPI was not reached, 24 months, and 4 months, respectively, and median PFS was 19.1 months, 12.3 months, and 2.9 months, respectively. In the cox proportional hazards model, poor InPI remained an independent prognostic factor for PFS and OS. Pre-infusion ferritin was negatively associated with CAR T-cell expansion normalized to baseline tumor burden. Spearman correlation analysis showed that pre-infusion ferritin and IL-6 levels positively correlated with the grade of CRS ( P = .0369 and P = .0117, respectively). The incidence of severe CRS was higher in patients with high IL-6 compared with patients with low IL-6 (26% vs . 9%, P = .0405). Pre-infusion ferritin, CRP and IL-6 were positively correlated with each peak values within the first month after infusion., Conclusions: Our results suggest that patients with elevated inflammation markers before CAR-T cell infusion are more likely to have poor prognosis., Competing Interests: 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., (Copyright © 2023 Liu, Jie, Nian, Wang, Wang, Ma, Jiang, Wu, Qiao, Chen, Cao, Yan, Shi, Cheng, Zhu, Sang, Li, Chen, Xu and Li.)

Background: Fat transplantation supported by supplementation with ASCs has become a reliable procedure for treating soft tissue defects. However, the unpredictable survival rates for grafted fat remains a challenge with post-transplantation ischemia causing tissue loss. MiR126, which regulates VEGF signaling, is an endothelial cell-specific miRNA known to play an essential role in angiogenesis. We hypothesized that increased miR126 expression in grafted ASCs may promote fat survival within an autologous fat transfer model., Methods: Rat adipose-derived stem cells were isolated, expanded ex vivo for three passages and then transduced with miR126. We used PCR to verify lentiviral transduction and ELISA to confirm VEGF expression. We then mixed autologous fat tissues from our rat model with transduced ASCs, augmented with a nonsense control or miR126 expression vector. These mixtures were used in the fat grafting procedure, completed via subcutaneous injection at three paravertebral points in each rat. Fat grafts were then harvested on days 4, 7, 14, and 28 post-transplant and evaluated for survival, neovascularization, and protein expression via western blot., Results: VEGF expression levels in ASCs, Con-ASCs, and miR126-ASCs were not significantly different. However, miR126-ASCs experienced significantly improved survival on days 7, 14, and 28 when compared with the other groups. These ASCs also presented with the greatest capillary density on days 7, 14, and 28 post-transplantation as well as increased p-ERK and p-AKT expression when compared to the other groups., Conclusion: This data suggests that miR126 augmentation of ASCs may help to enhance the survival and angiogenic capacity of transplanted fat tissues, and that this augmentation was not dependent on VEGF but rather the activation of the ERK/AKT pathway., No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: The number of publications on blepharoplasty is increasing rapidly. Bibliometric analysis can help surgeons quickly and systematically understand the current state of development. To our knowledge, there are no bibliometric studies on blepharoplasty, and therefore, we conducted this study to reveal research trends and perspectives of blepharoplasty., Methods: Relevant publications from 2002 to 2021 were extracted from the Web of Science Core Collection database. After manual screening, VOSviewer software and CiteSpace software were used to collect and analyze the acquired data., Results: A total of 1125 publications were included and the publications per year increased annually. Contributions from the USA led both quantity and quality. The University of California System was one of the most influential academic institutions. Aesthetic Plastic Surgery had the most publications, and Plastic and Reconstructive Surgery was the most frequently cited or co-cited journal. Massry GG and Hamra ST were the most prolific and co-cited authors, respectively. Additionally, Rohrich RJ had the highest number of citations per publication. References co-cited analysis identified that lower eyelid research was a hotspot. Keywords were mainly divided into 6 clusters, namely "lower lid blepharoplasty," "complications," "facial rejuvenation," "blepharoptosis," "upper blepharoplasty," and "Asian blepharoplasty and epicanthoplasty.", Conclusions: Blepharoplasty research is flourishing, and three clusters may be the hotspots: "Lower blepharoplasty and mid-face rejuvenation," "overall facial outcome and quality-of-life," and "Asian blepharoplasty and epicanthoplasty.", Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: Programmed cell death protein 1 (PD-1) antibody has been approved for a variety of tumors, but its effective rate is unsatisfactory. New evidence suggests that mast cells are an important component of the tumor microenvironment and are associated with resistance to immunotherapy, but the underlying mechanism is not clear., Methods: Bioinformatics analysis of patients with melanoma in TCGA-SKCM and GSE91061 was used to determine the prognostic value of mast cells and their association with anti-PD-1 immunotherapy. HMC-1 cells (mast cell line) and bone marrow-derived mast cells (BMMCs) were used to verify the effect of PD-1 antibody and cromolyn sodium in vitro. The mouse subcutaneous melanoma model was used to verify the effect of the PD-1 antibody on mast cells in vivo., Results: Bioinformatics analysis showed that mast cells were a poor prognostic factor associated with resistance to anti-PD-1 immunotherapy. PD-1 was expressed on the mast cell membrane. The PD-1 antibody promoted the release of histamine and cytokines from mast cells via the PI3K/AKT pathway and calcium signaling pathway. The activation of mast cells induced by PD-1 antibody could be partially inhibited by cromolyn sodium. In vivo, cromolyn sodium increased the efficacy of PD-1 antibody and decreased the infiltration of mast cells and the density of microvessels., Conclusion: PD-1 + mast cell activated by PD-1 antibody plays a negative role in the tumor microenvironment via the enhanced function of releasing histamine and cytokines. Inhibition of mast cell may provide a new solution to solve the low response rate of anti-PD-1 immunotherapy., (© 2022. The Author(s).)

438Severe skin injuries can cause serious problems, which could affect the patient's normal life, if not dealt properly in a timely and effective manner. It is an urgent requirement to develop personalized wound dressings with excellent antibacterial activity and biocompatibility to match the shape of the wound to facilitate clinical application. In this study, a bioink (GAQ) based on gelatin (Gel)/sodium alginate (SA)/ quaternized chitosan (QCS) was prepared, and GAQ hydrogel dressing grafting with dopamine (GADQ) was fabricated by an extrusion three-dimensional (3D) printing technology. QCS was synthesized by modifying quaternary ammonium group on chitosan, and its structure was successfully characterized by nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FT-IR). Our results showed that the GADQ hydrogel dressing that was double-crosslinked by EDC/ NHS and Ca 2+ had good tensile strength, considerable swelling ratio, and effective antioxidation properties. It also showed that GADQ1.5% had 93.17% and 91.06% antibacterial activity against Staphylococcus aureus and Escherichia coli , respectively . Furthermore, the relative survival ratios of fibroblast cells seeded on these hydrogels exceeded 350% after cultured for 7 days, which proved the biocompatibility of these hydrogels. Overall, this advanced 3D-printed GADQ1.5% hydrogels with effective antioxidation, excellent antibacterial activity and good biocompatibility had a considerable application potential for wound healing., Competing Interests: 449The authors declare no conflicts of interest., (Copyright: © 2023 Lu Y, Xu J, Su Y, et al.)

Optimum tillage practices can create a suitable soil environment, and they improve the soil nutrient status to ensure crop development and yield. In this study, we evaluated the influences of six tillage practices on soil nutrients and maize yields from 2017 to 2019 in fluvo-aquic soil in the North China Plain. The field experiment was carried out by a split design with rotary tillage (RT) and deep tillage (DT) in wheat season in the main plot and no-tillage (NT), subsoiling between the row (SBR), and subsoiling in the row (SIR) in maize season in the subplot. The results showed that the soil nutrient content was higher under the treatments with rotary tillage in the wheat season in the 0-20 cm soil layer, while in the 20-40 cm soil layer, the soil nutrient content was higher under the treatments with deep tillage in the wheat season. The integrated principal component scores indicated that the soil nutrients had improved in the second year. The ecosystem multifunctionality (EMF) index was higher with the treatments with rotary tillage in wheat season in the 0-20 cm soil layer, while it was the highest under DT-SIR at 20-40 cm. Correlation analysis showed that the soil EMF index correlated significantly ( p < 0.05) with the soil nutrient content mainly in the 0-40 cm soil layer. The higher maize yield was under the treatments with deep tillage compared to that under the treatments with rotary tillage in the wheat season. The yield-increasing effect was higher under the treatments with subsoiling than those utilizing no-till in the maize season, with the highest average yield of 13,910 kg hm -2 in the DT-SIR during the three years. Maize yield was strongly correlated with nutrients in the subsoil layer. The higher yield stability was found under RT-NT. To sum up, during the three-year experiment, rotary tillage in the wheat season combined with subsoiling in the maize season improved the soil nutrient content and the EMF index in the 0-20 cm layer, while the combination of deep tillage in the wheat season and subsoiling in the maize season improved those indices in the 20-40 cm soil layer, and increased the maize yield, the best one was under DT-SIR.

Nitrogen is a vital element for soil fertility and crop productivity. The transformation of nitrogen is directly affected by tillage practices for the disturbing soil. The characteristics of different nitrogen forms under different tillage modes are still unclear. A 3-year cycle tillage experiment was carried out to assess the combination of rotary tillage (RT), deep tillage (DT), and shallow rotary tillage (SRT) on nitrogen transformation and distribution, wheat yield and nitrogen balance in fluvo-aquic soil from Huang-Huai-Hai Plain in China. The results showed the rotation tillage cycle with deep tillage in the first year increased the total nitrogen (TN), and the main nitrogen form content in 0-30 cm compared with continued rotary tillage (RT-RT-RT). Moreover, the nitrate (NO 3 - -N) and ammonium nitrogen (NH 4 + -N) content were improved in 20-40 cm by deep tillage practice with the highest value as 39.88 mg kg -1 under DT-SRT-RT. The time, tillage, and depth significantly affected the different nitrogen forms, but there was no effect on dissolved organic carbon (DON) and soil microbial biomass nitrogen (SMBN) by the interaction of time and tillage. Moreover, compared with RT-RT-RT, the rotation tillage promoted the spike number and kernels per spike of wheat, further increasing the wheat yield and nitrogen partial productivity, and with a better effect under DT-SRT-RT. The NO 3 - -N and NH 4 + -N trended closer and positively correlated with wheat yield in 0-40 cm in 2019. The rotation tillage with deep tillage improved the different forms of nitrogen in 0-30 cm, wheat yield, and nitrogen partial productivity, and decreased the apparent nitrogen loss. It was suggested as the efficiency tillage practice to improve nitrogen use efficiency and crop yield in this area.

We want to explore the analgesic brain effect of the moxibustion at heat-sensitized Yaoyangguan (GV3) in patients with lumbar disc herniation (LDH) and myofascial pain syndrome (MPS). In an assessor-blinded observational study, we will include 15 LDH and 15 MPS. They will accept same treatment of heat-sensitive moxibustion at Yaoyangguan (GV3). The resting-state functionality magnetic resonance imaging image data of brain activities before and after treatment will be analyzed by mean fractional amplitude of low-frequency fluctuation, regional homogeneity analysis and brain functional connection. We select seed of first sensory cortex, second sensory cortex, insula cortex, periaqueductal gray and anterior cingulate cortex as the regions of interest to analyse the relationship between brain functional connectivity of pain-related networks and clinical data. Our study could disclose key brain targets and central response characteristics of the analgesic brain effect and the brain functional connection of heat-sensitive moxibustion.

Background: Radiation-induced lung injury (RILI) is the most common and serious complication of chest radiotherapy. However, reported radioprotective agents usually lead to radiation resistance in tumor cells. The key to solving this problem is to distinguish between the response of tumor cells and normal lung epithelial cells to radiation damage., Methods: RNA-Seq was used to recognize potential target of alleviating the progression of RILI as well as inhibiting tumor growth. The activation of NLRP3 inflammasome in lung epithelial cells was screened by qRT-PCR, western blotting, immunofluorescence, and ELISA. An in vivo model of RILI and in vitro conditioned culture model were constructed to evaluate the effect of NLRP3/interleukin-1β on fibroblasts activation. ROS, ATP, and (NADP) + /NADP(H) level in lung epithelial cells was detected to explore the mechanism of NLRP3 inflammasome activation. The lung macrophages of the mice were deleted to evaluate the role of lung epithelial cells in RILI. Moreover, primary cells were extracted to validate the results obtained from cell lines., Results: NLRP3 activation in epithelial cells after radiation depends on glycolysis-related reactive oxygen species accumulation. DPYSL4 is activated and acts as a negative regulator of this process. The NLRP3 inflammasome triggers interleukin-1β secretion, which directly affects fibroblast activation, proliferation, and migration, eventually leading to lung fibrosis., Conclusions: Our study suggests that NLRP3 inflammasome activation in lung epithelial cells is essential for radiation-induced lung injury. These data strongly indicate that targeting NLRP3 may be effective in reducing radiation-induced lung injury in clinical settings., (© 2023. The Author(s).)

Hydroboration of styrene or vinylcyclohexane with the IMes(C 6 F 5 )BH + cation followed by deprotonation provided a convenient synthetic entry to the [B]=CHCH 2 R boraalkenes 9 a and 9 b. The in situ generated IMes(SCN)BH + system reacted similarly with 1,1-diphenylethene followed by deprotonation to give the isothiocyanato substituted boraalkene 9 c. The boraalkenes underwent [2+2] cycloaddition reactions with a small series of heterocumulenes to give the respective four-membered heterocycles. The [B]=CHCH 2 R+CO 2 cycloadducts 13 a and 13 b added the borane HB(C 6 F 5 ) 2 with cleavage of the central B-C σ-bond. CS 2 underwent an unusual reaction with the boraalkenes, namely insertion into the B=C bond with formation of the borylated dithioketene acetal under complete rupture of the strong B=C double bond. The intermediate dithiobora-β-lactone type intermediate was isolated in the case of the isothiocyanato-boraalkene reaction and characterized by X-ray diffraction., (© 2022 Wiley-VCH GmbH.)

We report a general method for the labeling of both CF 3 and CF 2 H groups in a broad range of chemical settings (aryl, oxide, sulfide). The method utilizes frustrated Lewis pair mediated selective C-F activation to formally substitute fluorine-19 with fluorine-18 in a two-step defluorination/radiofluorination process, and as such can utilize the target compounds as starting materials. The radiotracer precursors can be isolated as stable salts prior to radiofluorination. The method delivers good radiochemical yields and molar activities (up to 35.2±6.5 % non-decay corrected isolated activity yields and 12.0±1.7 GBq μmol -1 molar activities) and is shown to be applicable to biologically relevant compounds. The ability to utilize the target compound as the starting material and the synthetic simplicity of the method coupled with the ever-increasing use of CF 3 and CF 2 H groups in pharmaceuticals makes this method attractive for drug and radiotracer development., (© 2022 Wiley-VCH GmbH.)

Introduction: Urethral lengthening in phalloplasty could bring many postoperative complications, such as urethra fistula and stricture, which greatly affects the patient's mental health and quality of life., Aim: To describe a novel technique of vaginal mucosal graft for prelamination urethra (VMGPU) combined with modified urethral anastomosis (MUA) for the reconstruction of a neourethra., Methods: A retrospective study of transgender men between January 2006 and March 2021 was conducted. Patients were divided into three groups according to the surgical methods : traditional group（TG，VMGPU group（VG） and VMGPU+MUA group (VMG)., Main Outcome Measure: The main outcomes measures were demographics, surgical characteristics, complications, International Prostate Symptom Score（IPSS，Quality of Life（QOL） score，and voiding frequency conditions., Results: Of 80 eligible transgender men（TG:n = 39，VG:n = 31, VMG:n = 10), the urethral fistula developed in 19/39 (49%) patients in TG, 8/31 (26%) in VG, and 1/10 (10%) in VMG (P = 0.034). The urethral stricture formed in 15/39 (38%) patients in TG, 4/31 (13%) in VG, and 1/10 (10%) in VMG (P = 0.028). Compared with TG, the VG got more favorable IPSS. The QOL scores showed that patients in VG or VMG were more satisfied with their postoperative status., Clinical Implications: VMGPU combined with MUA may help reduce urethral complications for transgender men who wish to undergo phalloplasty with urethral lengthening., Strength & Limitations: VMGPU combined with MUA focuses on reducing the urethra-related complications in the anastomotic stoma between the fixed and the penile urethra, which has not been noticed in the past. The limitations of this study are that the retrospective study design is prone to bias; the study using VMGPU+MUA technique is only in the preliminary stage, and more cases are needed to prove its effectiveness; the median follow-up in VMG was only 2 years, and longer-term follow-up results are inconclusive; the IPSS, QOL, and the voiding frequency chart were not validated in transgender men., Conclusion: Our pilot study suggests that VMGPU combined with MUA may reduce the urethra-related complications, especially the urethral fistula in the anastomosis stoma between the fixed and the penile urethra. Gao H, Wu D, Kong X, et al. A Novel Technique of Urethroplasty Could Reduce Urethra-Related Complications in Phalloplasty With Urethral Lengthening. Sex Med 2022;10:100571., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

A reaction intermediate is a key molecular entity that has been used in explaining how starting materials converts into the final products in the reaction, and it is usually unstable, highly reactive, and short-lived. Extensive efforts have been devoted in identifying and characterizing such species via advanced physico-chemical analytical techniques. As an appealing alternative, trapping experiments are powerful tools in this field. This trapping strategy opens an opportunity to discover multicomponent reactions. In this work, we report various highly diastereoselective and enantioselective four-component reactions (containing alcohols, diazoesters, enamines/indoles and aldehydes) which involve the coupling of in situ generated intermediates (iminium and enol). The reaction conditions presented herein to produce over 100 examples of four-component reaction products proceed under mild reaction conditions and show high functional group tolerance to a broad range of substrates. Based on experimental and computational analyses, a plausible mechanism of this multicomponent reaction is proposed., (© 2022. The Author(s).)

Metastasis remains the primary cause of small cell lung cancer (SCLC)-related deaths. Growing evidence links tumor metastasis with a pre-metastatic microenvironment characterized by an anti-inflammatory response, immunosuppression, and the presence of tumor-derived exosomes. To clarify the relationships among these factors in SCLC, we analyzed SCLC patient samples as well as a mouse model. Among the infiltrating immune cells, our study focused on the tumor-associated macrophages (TAMs), that are well-known to promote tumor progression and metastasis. We found that high expression of the alternatively activated (M2) TAM marker, CD206 + was associated clinically with a poorer prognosis and metastasis state in patients with SCLC. Moreover, infiltrating macrophages (MØ) were found in the metastatic foci of an SCLC mouse model. Additionally, we observed dominant switching to M2 phenotype, accompanied by increased NLRP6 expression. Since tumor-derived exosomes are the key links between the tumor and its immune microenvironment, we further investigated whether SCLC-derived exosomes contributed to the MØ phenotype switch. Our findings showed for the first time that SCLC-derived exosomes induce the M2 switch via the NLRP6/NF-κB pathway, and thus, promote SCLC metastasis in vitro and in vivo. Collectively, these results indicate a novel mechanism by which SCLC-derived exosomes induce immunosuppression of distant MØ to promote systemic metastasis by activating NLRP6. Here, we highlight the close relationship between the tumor-derived exosomes, inflammasomes and immune microenvironment in SCLC metastasis., (© 2022. The Author(s).)

DNA methylation modification can regulate gene expression without changing the genome sequence, which helps organisms to rapidly adapt to new environments. However, few studies have been reported in non-model mammals. Giant panda ( Ailuropoda melanoleuca ) is a flagship species for global biodiversity conservation. Wildness and reintroduction of giant pandas are the important content of giant pandas' protection. However, it is unclear how wildness training affects the epigenetics of giant pandas, and we lack the means to assess the adaptive capacity of wildness training giant pandas. We comparatively analyzed genome-level methylation differences in captive giant pandas with and without wildness training to determine whether methylation modification played a role in the adaptive response of wildness training pandas. The whole genome DNA methylation sequencing results showed that genomic cytosine methylation ratio of all samples was 5.35%-5.49%, and the methylation ratio of the CpG site was the highest. Differential methylation analysis identified 544 differentially methylated genes (DMGs). The results of KEGG pathway enrichment of DMGs showed that VAV3 , PLCG2 , TEC and PTPRC participated in multiple immune-related pathways, and may participate in the immune response of wildness training giant pandas by regulating adaptive immune cells. A large number of DMGs enriched in GO terms may also be related to the regulation of immune activation during wildness training of giant pandas. Promoter differentially methylation analysis identified 1,199 genes with differential methylation at promoter regions. Genes with low methylation level at promoter regions and high expression such as, CCL5 , P2Y13 , GZMA , ANP32A , VWF , MYOZ1 , NME7 , MRPS31 and TPM1 were important in environmental adaptation for wildness training giant pandas. The methylation and expression patterns of these genes indicated that wildness training giant pandas have strong immunity, blood coagulation, athletic abilities and disease resistance. The adaptive response of giant pandas undergoing wildness training may be regulated by their negatively related promoter methylation. We are the first to describe the DNA methylation profile of giant panda blood tissue and our results indicated methylation modification is involved in the adaptation of captive giant pandas when undergoing wildness training. Our study also provided potential monitoring indicators for the successful reintroduction of valuable and threatened animals to the wild., Competing Interests: 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., (Copyright © 2022 Jie, Wu, Yang, He, Zhao, Ling, Huang, Yue, Yang and Zhang.)

Background: Depression is a common psychiatric disorder and has become a growing public health issue. Traditional Chinese medicine (TCM) tonic prescriptions have been clinically proven to be an effective treatment for depression., Purpose: This study aimed to identify the core prescription to improve depression among the numerous TCM tonic prescriptions., Methods and Results: First, we used meta-analysis to clarify the efficacy and safety of tonic prescriptions in depression among 37 studies and identified 16 effective tonic prescriptions. Second, we conducted data mining to analyze the tonic prescriptions and identified important nourishing herbs. Third, based on the data mining results, we constructed a Delphi experiment to investigate the effects of these important nourishing herbs in depression. Combining the results of Delphi expert questionnaires and weight analysis, a core TCM tonic prescription, Jianpi Tongmai formula (JPTMF) for the treatment of depression, was constructed and was composed of invigorating Spleen qi herbs. Fourth, we verified that JPTMF can improve chronic unpredictable mild stress (CUMS) induced depression-like behaviors in mice. Fifth, we predicted that the mechanism of JPTMF in the treatment of depression was mainly associated with chemical synaptic transmission and neuroinflammation through network pharmacology and determined preliminary confirmation through animal experiments., Conclusion: This study was undertaken to evaluate the efficacy of TCM tonic prescriptions on depression and construct a core TCM tonic prescription, JPTMF, through a progressive analysis. Network pharmacology and animal experiments verified the reliability of JPTMF. The proposal of JPTMF is of innovative significance, and may provide far-reaching implications for improving depression by using nourishing herbs. Furthermore, the integrated methods applied in this study provide an innovative paradigm for the standardization and scientific basis of TCM research., (Copyright © 2022. Published by Elsevier GmbH.)

Gardnerella overgrowth is the primary cause of bacterial vaginosis (BV), a common vaginal infection with incidences as high as 23-29% worldwide. Here, we studied the pathogenicity, drug resistance, and prevalence of varying Gardnerella spp. We isolated 20 Gardnerella strains from vaginal samples of 31 women in local China. Ten strains were then selected via phylogenetic analysis of cpn60 and vly gene sequences to carry out genome sequencing and comparative genomic analysis. Biofilm-formation, sialidase, and antibiotic resistance activities of the strains were characterized. All strains showed striking heterogeneity in genomic structure, biofilm formation and drug resistance. Two of the ten strains, JNFY3 and JNFY15, were classified as Gardnerella swidsinskii and Gardnerella piotii , respectively, according to their phenotypic characteristics and genome sequences. In particular, seven out of the ten strains exhibited super resistance (≥ 128 μg/mL) to metronidazole, which is the first line of treatment for BV in China. Based on the biochemical and genomic results of the strains, we proposed a treatment protocol of prevalent Gardnerella strains in local China, which provides the basis for accurate diagnosis and therapy., Competing Interests: 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., (Copyright © 2022 Zhang, Lu, Zhu, Wang, Jie, Li, Dong, Li, Zhang and Gu.)

Cadmium (Cd) contamination seriously threatens the soil health and food safety. Combination of amendment and accumulator plant is a green and effective technique to improve phytoremediation of Cd-contaminated alkaline soil. In this study, a potting experiment was conducted to investigate the effect of sulfur on Cd phytoextraction by Cichorium intybus (chicory). Soil chemical and microbial properties were determined to reveal the mechanism of sulfur-assisting Cd phytoremediation by chicory. Soil pH decreased from 7.77 to the lowest 7.30 with sulfur addition (0.6, 0.9 and 1.2 g kg -1 , LS, MS and HS treatment); Electric conductivity, sulfate anion and available cadmium concentration increased gradually with increasing sulfur doses. Cd concentration of shoot and root significantly increased from 1.47 to 4.43 mg kg -1 , 6.15 to 20.16 mg kg -1 by sulfur treatment relative to CK, which were attributed to increased available Cd concentration induced by decreased pH. Sulfur treatments significantly increased the Cd bioconcentration factor by 64.1%, 118.6%, 201.0% for shoot, 76.3%, 145.6% and 227.7% for root under LS, MS and HS relative to CK treatment, respectively (P < 0.05). However, only MS treatment significantly improved the Cd removal efficiency by 82.9% in comparison of CK treatment (P < 0.05). Microbial community diversity measured by 16SrRNA showed that Thiobacillus and Actinobacteria were the key and dominant strains of soil microbial communities after sulfur addition, which played a pivotal role in the process of sulfur oxidation involved in decrease of soil pH and the transformation of Cd forms. Correlation analysis and path analysis by structural equation model indicated that soil sulfate anion and Thiobacillus directly affected Cd removal efficiency by chicory in Cd-contaminated alkaline soil. This suggests that combination of sulfur and chicory may provide a way to promote Cd bioaccumulation for phytoremediation of Cd-contaminated alkaline soil., 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 B.V. All rights reserved.)

Background: Fetal macrosomia is associated with an increased risk of several maternal and newborn complications. Antenatal predication of fetal macrosomia remains challenging. We aimed to develop a nomogram model for the prediction of macrosomia using real-world clinical data to improve the sensitivity and specificity of macrosomia prediction., Methods: In the present study, we performed a retrospective, observational study based on 13,403 medical records of pregnant women who delivered singleton infants at a tertiary hospital in Shanghai from 1 January 2018 through 31 December 2019. We split the original dataset into a training set (n = 9382) and a validation set (n = 4021) at a 7:3 ratio to generate and validate our model. The candidate variables, including maternal characteristics, laboratory tests, and sonographic parameters were compared between the two groups. A univariate and multivariate logistic regression was carried out to explore the independent risk factors for macrosomia in pregnant women. Thus, the regression model was adopted to establish a nomogram to predict the risk of macrosomia. Nomogram performance was determined by discrimination and calibration metrics. All the statistical analysis was analyzed using R software., Results: We compared the differences between the macrosomic and non-macrosomic groups within the training set and found 16 independent risk factors for macrosomia (P < 0.05), including biparietal diameter (BPD), head circumference (HC), femur length (FL), amniotic fluid index (AFI) at the last prenatal examination, pre-pregnancy body mass index (BMI), and triglycerides (TG). Values for the areas under the curve (AUC) for the nomogram model were 0.917 (95% CI, 0.908-0.927) and 0.910 (95% CI, 0.894-0.927) in the training set and validation set, respectively. The internal and external validation of the nomogram demonstrated favorable calibration as well as discriminatory capability of the model., Conclusions: Our model has precise discrimination and calibration capabilities, which can help clinical healthcare staff accurately predict macrosomia in pregnant women., (© 2022. The Author(s).)

Lithium-sulfur (Li-S) batteries are considered to be one of the candidates for high-energy density storage systems due to their ultra-high theoretical specific capacity of 1675 mA h g -1 . However, problems of rapid capacity decay, sharp expansion in volume of the active material, and the shuttle effect have severely restricted their subsequent development and utilization. Herein, we design a nitrogen-doped porous carbon nanofiber (NPCNF) network as a sulfur host by the template method. The NPCNF shows a feather-like structure. After loading sulfur, the NPCNF/S composite can maintain a hierarchically porous structure. A high discharge capacity of 1301 mA h g -1 is delivered for the NPCNT/S composite at 0.1C. The reversible charge/discharge capacity at 2C is 576 mA h g -1 , and 700 mA h g -1 is maintained after 500 cycles at 0.5C. The high electrochemical performance of this NPCNT/S composite is attributed to the synergy effects of abundant N active sites and high electrical conductivity of the material., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Both the giant panda ( Ailuropoda melanoleuca ) and red panda ( Ailurus fulgens ) belong to the order Carnivora, but have changed their dietary habits to eating bamboo exclusively. The convergent evolution characteristics of their morphology, genome and gut flora have been found in the two pandas. However, the research on the convergent adaptation of their digestion and metabolism to the bamboo diet, mediated by the dietary shift of the two pandas at the gene-expression and epigenetic regulation levels, is still lacking. We therefore used RNA sequencing among five species (two pandas and three non-herbivore mammals) and bisulfite sequencing among three species (two pandas and a carnivore ferret) to sequence key digestion and metabolism tissues (stomach and small intestine). Our results provide evidence that the convergent differentially expressed genes (related to carbohydrate utilization, bile secretion, Lys and Arg metabolism, vitamin B12 utilization and cyanide detoxification) of the two pandas are adaptive responses to the bamboo diet containing low lipids, low Lys and Arg, low vitamin B12 and high cyanide. We also profiled the genome-wide methylome maps of giant panda, red panda and ferret, and the results indicated that the promoter methylation of the two pandas may regulate digestive and metabolic genes to adapt to sudden environmental changes, and then, transmit genetic information to future generations to evolve into bamboo eaters. Taken together, our study provides new insights into the molecular mechanisms of the dietary shift and the adaptation to a strict bamboo diet in both pandas using comparative transcriptomics and methylomics.

The efficacy of apatinib has been confirmed in the treatment of solid tumors, including non-small-cell lung cancer (NSCLC). However, the direct functional mechanisms of tumor lethality mediated by apatinib and the precise mechanisms of drug resistance are largely unknown. In this study, we demonstrated that apatinib could reprogram glutamine metabolism in human NSCLC via a mechanism involved in amino acid metabolic imbalances. Apatinib repressed the expression of GLS1, the initial and rate-limiting enzyme of glutamine catabolism. However, the broken metabolic balance led to the activation of the amino acid response (AAR) pathway, known as the GCN2/eIF2α/ATF4 pathway. Moreover, activation of ATF4 was responsible for the induction of SLC1A5 and ASNS, which promoted the consumption and metabolization of glutamine. Interestingly, the combination of apatinib and ATF4 silencing abolished glutamine metabolism in NSCLC cells. Moreover, knockdown of ATF4 enhanced the antitumor effect of apatinib both in vitro and in vivo. In summary, this study showed that apatinib could reprogram glutamine metabolism through the activation of the AAR pathway in human NSCLC cells and indicated that targeting ATF4 is a potential therapeutic strategy for relieving apatinib resistance., (© 2022. The Author(s).)

Ethnopharmacological Relevance: The Bupi Yishen Formula (BYF) is a patented Chinese herbal compound that has been long used to treat chronic kidney disease (CKD) in the clinic. However, its main active ingredients and underlying mechanisms remain to be elucidated., Aim: Identify the major active ingredients of BYF and investigate its protective effects and specific molecular mechanisms in renal fibrosis., Methods: First, we performed network pharmacology analysis combined with molecular docking to predict the main active compounds, potential therapeutic targets, and intervention pathways that might exert the anti-fibrotic effect of BYF in the kidney. Then, we validated the predictions in both adenine-induced CKD rats and TGFβ1-induced HK-2 cells., Results: A total of 233 common targets, 25 core targets, and 10 main active compounds from BYF were selected by network pharmacology analyses. Then, GO and KEGG functional enrichment analyses indicated that the renoprotection conferred by BYF against renal fibrosis was mainly associated with the PI3K/AKT signaling. Besides, the molecular docking showed that the 10 main active compounds of BYF were closely docked with three main PI3K/AKT pathway proteins. During the experimental validations, BYF improved renal impairment and alleviated fibrosis by inhibiting the PI3K/AKT signaling activity in the kidney of adenine-induced CKD model rats. Moreover, increased PI3K/AKT signaling activation was associated with fibrotic phenotype changes in adenine-induced CKD rats and TGFβ1-induced HK-2 cells. On the other hand, BYF treatment reduced PI3K/AKT signaling activation and decreased renal fibrogenesis in a dose-dependent manner, thereby indicating that PI3K/AKT signaling was essential for BYF to exert its anti-fibrotic effects. Finally, the inhibitory effect of BYF on renal fibrogenesis was not enhanced while blocking the PI3K/AKT pathway with a broad spectrum PI3K inhibitor (LY294002)., Conclusion: In the present study, we applied a comprehensive strategy based on systemic pharmacology to reveal the anti-fibrotic mechanisms of BYF, at least partially, through the inhibition of PI3K/AKT signaling activation. We also identified BYF as a potential therapeutic agent for renal fibrosis and CKD progression., (Copyright © 2022 Elsevier B.V. All rights reserved.)