[Non-targeted renal metabolomics reveals multi-target effects of Dahuang Zhechong Pills on renal aging in rats].

This study aims to observe the effects of the traditional Chinese medicine prescription Dahuang Zhechong Pills(DHZCP on renal aging and explore its potential multi-target effects. Rats were assigned into the normal, model, DHZCP, and vitamin E(VE)groups. Firstly, the rat model of D-galactose(D-gal)-induced renal aging was established. During the modeling period, the rats in the 4 groups were administrated with double distilled water, double distilled water, DHZCP suspension, and VE suspension, respectively,by gavage every day. On day 60 of intervention, the indicators of renal aging and injury in rats were measured, including the function,histopathological characteristics, senescence-associated ß-galactosidase( SA-ß-gal) staining, and expression levels of Klotho and proteins associated with cell cycle arrest and senescence-associated secretory phenotype(SASP) in the renal tissue. Moreover, nontargeted metabolomic analysis of the renal tissue was performed for the 4 groups of rats to screen out the potential biomarkers and metabolic pathways. Finally, the signaling pathways of key targets were preliminarily validated. The results showed that DHZCP and VE significantly improved the renal function, histopathological features of renal tubular/interstitial tissue, and degree of SA-ß-gal staining, up-regulated the expression level of Klotho, and down-regulated the expression levels of proteins associated with cell cycle arrest and SASP in the renal tissue of the aging rats. In addition, DHZCP and VE regulated the metabolites in the renal tissue of the aging rats. There were 21 common differential metabolites. Among them, 5 differential metabolites were significantly increased in the aging rats and recovered after DHZCP or VE treatment, and they were involved in the lipid metabolism and energy metabolism pathways. The areas under the curves of the groups in comparison varied within the range of 0. 88-1. DHZCP regulated multiple signaling pathways, such as the adenosine monophosphate-activated protein kinase(AMPK), cyclic guanosine monophosphate-protein kinase G( c GMP-PKG), cyclic adenylic acid( c AMP), phosphatidylinositol-3-kinase-protein kinase B( PI3K-Akt), mammalian target of rapamycin(mTOR), and autophagy signaling pathways. In addition, it affected the multiple metabolic pathways, such as renin secretion, longevity regulation pathway, diabetic cardiomyopathy, and niacin and nicotinamide metabolism. DHZCP and VE significantly up-regulated the expression level of the key proteins in the AMPK signaling pathway in the renal tissue of the aging rats. In all, DHZCP and VE could mitigate renal aging and injury. DHZCP exerted multi-target effects via multiple signaling pathways and metabolic pathways in the kidney, in which the AMPK signaling pathway may be one of the key targets for action.

TGFß-mediated inhibition of hypodermal adipocyte progenitor differentiation promotes wound-induced skin fibrosis.

Aberrant activation of dermal fibroblasts during wound healing often leads to debilitating fibrotic changes in the skin, such as scleroderma and keloids. However, the underlying cellular and molecular mechanisms remain elusive. Here, we established a wound-induced skin fibrosis (WISF) mouse model in mature adult mice, characterised by excessive deposition of collagen bundles, loss of dermal adipocytes, and enrichment of DPP4+Ly6A+THY1+ hypodermal interstitial adipocyte progenitors (HI-APs) and pericytes, resembling human fibrotic skin diseases. This WISF model exhibited an age-dependent gain of fibrotic characteristics, contrasting with the wound-induced hair neogenesis observed in younger mice. Through comprehensive analyses of the WISF, we delineated a trajectory of fibroblast differentiation that originates from HI-APs. These progenitors highly expressed several extracellular matrix (ECM) genes and exhibited a TGFß pathway signature. TGFß was identified as the key signal to inhibit the adipogenic potential and maintain the fibrogenic potential of dermal APs. Additionally, administering a TGFß receptor inhibitor to wound scar reduced the abundance of ECM-producing APs. Finally, analysis of human scleroderma skin tissues revealed a negative correlation between the expression of AP-, ECM-, and TGFß pathway-related genes and PPARG. Overall, this study establishes a wound-induced skin fibrosis mouse model and demonstrates that TGFß-mediated blockage of HI-AP differentiation is crucial for driving fibrotic pathology. Targeting HI-APs and adipogenesis may provide novel avenues for developing disease-modifying therapies for fibrotic skin diseases.

Bioinspired Total Synthesis of Cephalotaxus Diterpenoids and Their Structural Analogues.

Herein, we present a unified chemical synthesis of three subgroups of cephalotaxus diterpenoids. Key to the success lies in adopting a synthetic strategy that is inspired by biosynthesis but is opposite in nature. By employing selective one-carbon introduction and ring expansion operations, we have successfully converted cephalotane-type C18 dinorditerpenoids (using cephanolide B as a starting material) into troponoid-type C19 norditerpenoids and intact cephalotane-type C20 diterpenoids. This synthetic approach has enabled us to synthesize cephinoid H, 13-oxo-cephinoid H, 7-oxo-cephinoid H, fortalpinoid C, 7-epi-fortalpinoid C, cephanolide E, and 13-epi-cephanolide E. Furthermore, through the development of an intermolecular asymmetric Michael reaction between ß-oxo esters and ß-substituted enones, we have achieved the enantioselective synthesis of advanced intermediates within our synthetic sequence, thus formally realizing the asymmetric total synthesis of the cephalotaxus diterpenoids family.

Selective Construction of C-S/S-N Bonds from N-Substituted O-Thiocarbamates and Indoles under Transition-Metal-Free Conditions.

A method for the selective construction of S-N/C(sp2)-S bonds using N-substituted O-thiocarbamates and indoles as substrates is reported. This protocol features good atom utilization, mild conditions, short reaction time, and wide substrate scope, which can provide a convenient path for the functionalization of indoles. In addition, the reaction could be scaled up on gram scale, showing potential application value in industry synthesis.

[Blaps rynchopetera combined with cyclophosphamide affects proliferation and apoptosis of lung cancer cells via Wnt/ß-catenin signaling pathway].

This study aims to investigate the effects of Blaps rynchopetera Fairmaire and/or cyclophosphamide on the proliferation and apoptosis of lung cancer cells and decipher the underlying mechanism. B. rynchopetera and cyclophosphamide-containing serum and blank serum were prepared from SD rats. Cell counting kit-8(CCK-8) assay was employed to examine the proliferation of lung cancer cell lines A549 and Lewis treated with corresponding agents. The Jin's formula method was used to evaluate the combined effect of the two drugs. According to the evaluation results, appropriate drug concentrations and lung cancer cell line were selected for subsequent experiments, which included control, B. rynchopetera, cyclophosphamide, B. rynchopetera + cyclophosphamide, and B. rynchopetera + Wnt/ß-catenin pathway agonist lithium chloride(LiCl) groups. Immunocytochemistry was employed to measure the expression of proliferation-related proteins in Lewis cells after drug interventions. Flow cytometry was employed to determine the cell cycle and apoptosis. The expression levels of proliferating cell nuclear antigen(PCNA), cyclinD1, B-cell lymphoma 2(Bcl-2), Bcl-2-assiocated X protein(Bax), Wnt1, and ß-catenin were determined by Western blot. The results showed that B. rynchopetera and/or cyclophosphamide significantly inhibited the proliferation of A549 and Lewis cells. Compared with B. rynchopetera alone, the combination increased the inhibition rate on cell proliferation. The combination of B. rynchopetera and cyclophosphamide demonstrated a synergistic effect according to Jin's formula-based evaluation. Compared with the control group, the B. rynchopetera, cyclophosphamide, and B. rynchopetera + cyclophosphamide groups showed increased proportion of Lewis cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and ß-catenin. Compared with the cyclophosphamide group, the combination group showed increased proportion of cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and ß-catenin. Compared with the B. rynchopetera group, the B. rynchopetera + LiCl group had deceased proportion of cells in G_0/G_1 phase, decreased apoptosis rate, down-regulated expression of Bax, and up-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and ß-catenin. The results indicated that B. rynchopetera could inhibit the proliferation, arrest the cell cycle, and induce the apoptosis of lung cancer cells by inhibiting the Wnt/ß-catenin signaling pathway. Moreover, B. rynchopetera had a synergistic effect with cyclophosphamide.

Effects of neutrophil fate on inflammation.

INTRODUCTION: Neutrophils are important participants in the innate immune response. They rapidly and efficiently identify and clear infectious agents by expressing large numbers of membrane receptors. Upon tissue injury or pathogen invasion, neutrophils are the first immune cells to reach the site of injury and participate in the inflammatory response. MATERIALS AND METHODS: A thorough search on PubMed related to neutrophil death or clearance pathways was performed. CONCLUSION: Inflammatory response and tissue damage can be aggravated when neutrophils are not removed rapidly from the site of injury. Recent studies have shown that neutrophils can be cleared through a variety of pathways, including non-inflammatory and inflammatory death, as well as reverse migration. Non-inflammatory death pathways include apoptosis and autophagy. Inflammatory death pathways include necroptosis, pyroptosis and NETosis. This review highlights the basic properties of neutrophils and the impact of their clearance pathways on the inflammatory response.

Occupational protection behavior and its influencing factors of newly recruited nurses.

AIM: Aim The objective of this study was to understand the occupational protective behaviors of newly recruited nurses and explore the influencing factors. METHODS: A convenience sampling method was used to select newly recruited nurses in our hospital from July 2018 to November 2019. The survey was conducted using the general information questionnaire, work attitude scale (Wa), and occupational protective behavior scale. RESULTS: The total score of occupational protective behaviors of 150 newly enrolled nurses was 18.94 ± 3.59. There was a significant negative correlation between work attitude score and occupational protective behaviors (r = -0.324, p < 0.001). Multiple linear regression analysis showed that gender, previous participation in nursing skill-based competitions, experience of needlestick injuries before recruit, work attitude score, average daily sleep time (p < 0.05) were independent factors influencing occupational protective behaviors. CONCLUSIONS: The overall occupational protective awareness of newly enrolled nurses is relatively weak and needs to be further improved. The group's ability to improve occupational protective behaviors may be positively impacted through increased adaptability, improved sleep, active participation in nursing skill-based competitions, strengthening guidance and education on occupational protection.

Design of a binary metal micron grating and its application in near-infrared hot-electron photodetectors.

Metal plasmonic nano-gratings possess a high absorption ability and exhibit potential applications in sensing, hot-electron photodetection, metasurfaces, etc. However, the fabrication techniques of high-quality nano-gratings are challenging. In this article, a binary metal micron grating for near-infrared hot-electron photodetectors (HEPDs) is designed in which the surface plasmons are excited by high-diffraction-order modes. The high-diffraction-order micron grating can be fabricated by conventional lithography and has a significantly higher tolerance in the grating parameters than a nano-grating. The range of absorption greater than 70% is ∼3 times that of a nano-grating. Moreover, an interesting relationship between the resonant wavelength and the grating duty cycle is found. When the high-diffraction-order micron grating is applied in metal-insulator-metal HEPDs, a high zero-biased responsivity of 0.533 mA/W is achieved.

Excitation of out-of-plane lattice plasmons in dislocated nanostructures through near-field coupling.

Out-of-plane lattice plasmons (OLPs) show great potential in realizing high-quality factors due to the strong interparticle coupling. However, the strict conditions of oblique incidence bring challenges to experimental observation. This Letter proposes a new, to the best of our knowledge, mechanism to generate OLPs: through near-field coupling. Notably, with specially designed nanostructure dislocation, the strongest OLP can be achieved at normal incidence. The direction of energy flux of the OLPs is mainly determined by the wave vectors of Rayleigh anomalies. We further found that the OLP exhibits symmetry-protected bound states in the continuum characteristic, which explains the failure of previously reported symmetric structures to excite OLPs at normal incidence. Our work extends the understanding of the OLP and brings benefit to promote the flexible design of functional plasmonic devices.

[Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia].

OBJECTIVE: To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML). METHODS: The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed. RESULTS: Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified). CONCLUSION: D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.

Detrimental effects of fresh frozen plasma transfusions on postoperative outcomes in patients undergoing liver resection for hepatocellular carcinoma.

BACKGROUND: Perioperative fresh frozen plasma (FFP) is commonly transfused to patients undergoing liver resection for hepatocellular carcinoma (HCC), but its impacts in this population remain unknown. This study aimed to investigate the association of perioperative FFP transfusion with short-term and long-term outcomes in these patients. METHODS: We retrospectively identified and retrieved clinical data for HCC patients undergoing liver resection between March, 2007 and December, 2016. Study outcomes included postoperative bacterial infection, extended length of stay (LOS) and survival. Propensity score (PS) matching was used to determine the association of FFP transfusion with each outcome. RESULTS: A total of 1427 patients were included, and 245 of them received perioperative FFP transfusions (17.2%). Patients received perioperative FFP transfusions were older, underwent liver resection in the earlier time period, and had more extensive resection, poorer clinical conditions, and higher proportions of receiving other blood components. Perioperative FFP transfusion was associated with higher odds of both postoperative bacterial infection (OR = 1.77, p = 0.020) and extended LOS (OR = 1.93, p=<0.001), and the results remained similar after PS-matching. However, perioperative FFP transfusion did not significantly affect survival in these patients (HR = 1.17, p = 0.185). A potential association of postoperative FFP transfusions and poorer 5-year but not overall survival was observed in a subgroup of patients with low postoperative albumin levels after PS-matching. CONCLUSION: Perioperative FFP transfusions were associated with poorer short-term postoperative outcomes in HCC patients undergoing liver resection, including postoperative bacterial infection and extended LOS. Reducing perioperative FFP transfusions has the potential to improve their postoperative outcomes.

An inhibitor with GSK3ß and DYRK1A dual inhibitory properties reduces Tau hyperphosphorylation and ameliorates disease in models of Alzheimer's disease.

Since Alzheimer's disease (AD) is a complex and multifactorial neuropathology, the discovery of multi-targeted inhibitors has gradually demonstrated greater therapeutic potential. Neurofibrillary tangles (NFTs), the main neuropathologic hallmarks of AD, are mainly associated with hyperphosphorylation of the microtubule-associated protein Tau. The overexpression of GSK3ß and DYRK1A has been recognized as an important contributor to hyperphosphorylation of Tau, leading to the strategy of using dual-targets inhibitors for the treatment of this disorder. ZDWX-12 and ZDWX-25, as harmine derivatives, were found good inhibition on dual targets in our previous study. Here, we firstly evaluated the inhibition effect of Tau hyperphosphorylation using two compounds by HEK293-Tau P301L cell-based model and okadaic acid (OKA)-induced mouse model. We found that ZDWX-25 was more effective than ZDWX-12. Then, based on comprehensively investigations on ZDWX-25 in vitro and in vivo, 1) the capability of ZDWX-25 to show a reduction in phosphorylation of multiple Tau epitopes in OKA-induced neurodegeneration cell models, and 2) the effect of reduction on NFTs by 3xTg-AD mouse model under administration of ZDWX-25, an orally bioavailable, brain-penetrant dual-targets inhibitor with low toxicity. Our data highlight that ZDWX-25 is a promising drug for treating AD.

Effects of COVID-19 home quarantine on pregnancy outcomes of patients with gestational diabetes mellitus: a retrospective cohort study.

OBJECTIVE: This study aimed to evaluate the effects of the home quarantine on pregnancy outcomes of gestational diabetes mellitus (GDM) patients during the COVID-19 outbreak. METHODS: The complete electronic medical records of patients with GDM with home quarantine history were collected and classified into the home quarantine group from 24 February 2020 to 24 November 2020. The same period of patients with GDM without home quarantine history were included in the control group from 2018 to 2019. The pregnant outcomes of the home quarantine and control groups were systematically compared, such as neonatal weight, head circumference, body length, one-minute Apgar score, fetal macrosomia, and pre-term delivery. RESULTS: A total of 1358 patients with GDM were included in the analysis, including 484 in 2018, 468 in 2019, and 406 in 2020. Patients with GDM with home quarantine in 2020 had higher glycemic levels and adverse pregnancy outcomes than in 2018 and 2019, including higher cesarean section rates, lower Apgar scores, and higher incidence of macrosomia and umbilical cord around the neck. More importantly, the second trimester of home quarantine had brought a broader impact on pregnant women and fetuses. CONCLUSION: Home quarantine has aggravated the condition of GDM pregnant women and brought more adverse pregnancy outcomes during the COVID-19 outbreak. Therefore, we suggested governments and hospitals strengthen lifestyle guidance, glucose management, and antenatal care for patients with GDM with home quarantine during public health emergencies.

High-performance plasmonic polymer modulators through mode hybridization and electro-thermomechanical effects.

In this work, an electro-optical polymer modulator with double-layered gold nanostrips, a polymer nanograting, and a metal substrate is proposed and designed. Interestingly, mode hybridization between the Fabry-Pérot (F-P) and anti-bonding modes is formed, and strongly depends on the nanograting size, which can be controllably modulated by an injection current. The simulation and calculation results show that the temperature sensitivity and large structural sensitivity for the polymer modulator could remain constant during the current-tuning process, and a near-zero reflectance and a low linewidth of 13.8 nm in the red region corresponding to a high quality (Q) factor of 51 is achieved. In addition, a large redshift of 60.7 nm and a super-high modulation depth of 424 are obtained at only 8 µA.

Low-loss and broadband cascaded SiN RGB coupler with dual-mode interference.

We design and demonstrate a cascaded SiN-based RGB coupler with dual-mode interference (DMI) for a micro laser scanning image projector. The DMI configuration in SiN-based waveguides mitigates the adverse effects of self-image point deviation caused by wavelength dispersion, achieving decreased device length and high transmission efficiency. The underlying mechanisms are discussed based on coupled-mode theory and 3D finite difference time domain simulation. A small footprint of 3µm×70µm is achieved for the RGB coupler device without input/output circuits, and the insertion losses are less than 0.56 dB at RGB wavelengths. There are two orders of magnitude reduction in device length as compared with the conventional S i O 2-based RGB coupler, which greatly promotes the miniaturization of the couplers and displays integration advantages with a laser diode and waveguide photodetector. In addition, the 3 dB bandwidth is over 50 nm for the coupler, and it demonstrates good fabrication tolerance. This design can further be integrated into visible light communication systems and applied to visible light integrated photonics.

Insight into interfacial adsorption behavior of high-density lipoprotein hydrolysates regulated by carboxymethyl dextrin and in vitro digestibility of curcumin loaded high internal phase emulsions.

The interaction between high-density lipoprotein hydrolysate hydrolyzed by trypsin (EHT) and carboxymethyl dextrin (CMD) at pH 7.0, and in vitro digestibility of high internal phase emulsions (HIPEs) were studied. The particle size of EHT/CMD mixtures increased from 207.2 nm to 1229.6 nm with increase of the ratio of EHT to CMD from 8:1 to 1:2. The proportion of EHT adsorbed on the surface increased from 60.83 % to 80.81 %, forming thicker interfacial layer, exhibiting higher resistance to centrifugation and ionic strength. And more uniform proton density distribution and shorter relaxation time (T2) were charactered in HIPEs formed by mixtures. Rheological analysis further proved that CMD could lead to high viscosity, high elasticity, excellent oscillation performance of HIPEs. The spatial and electrostatic repulsion forces reduced the aggregation of oil droplets and promoted the formation of more mixed micelles, improving the bioaccessibility of curcumin. These findings provided theoretical strategies for lipid-soluble nutrients delivery systems.

OSA-linear dextrin enhances the compactness of pea protein isolate nanoparticles: Increase of high internal phase emulsions stability.

The pea protein isolate nanoparticles/octenyl succinic anhydride linear dextrin (PPINs/OSA-LD) composite particles were fabricated by heating at acidic condition. Heating treatment not only made OSA-LD dissolve, but also promoted the hydrophobic interactions between PPINs and OSA-LD. With the increase of OSA-LD content, the average diameter of composite particles decreased due to the avoidance of hydrophobic aggregation between PPINs during heating, and the composite particles became more compact and regular. The high internal phase emulsions (HIPEs) stabilized by composite particles exhibited smaller droplet size, higher viscosity and modulus attributing to the formation of denser interfacial layer. The results of low field nuclear magnetic resonance proved that the HIPEs stabilized by composite particles showed more uniform distribution of water and oil. This work provided a facile method to fabricate composite particles, which had excellent capacity to stabilize the HIPEs.

Altered Gut Microbial Profile Accompanied by Abnormal Fatty Acid Metabolism Activity Exacerbates Endometrial Cancer Progression.

Endometrial cancer (EC) is the most prevalent gynecological malignancy, with a higher risk in obese woman, indicating the possibility of gut microbiota involvement in EC progression. However, no direct evidence of a relationship between EC and gut microbiota in humans has been discovered. Here, we performed 16S rRNA sequencing to explore the relationship between dysbiosis of gut microbiota and cancer development in different types of EC patients. The results clearly show the differential profiles of gut microbiota between EC patients and normal participants as well as the association between gut microbiota and EC progression. Targeted metabolomics of plasma revealed an increased level of C16:1 and C20:2, which was positively associated with the abundance of Ruminococcus sp. N15.MGS-57. The higher richness of Ruminococcus sp. N15.MGS-57 in EC subjects not only was positively associated with blood C16:1 and C20:2 but also was negatively correlated with betalain and indole alkaloid biosynthesis. Furthermore, the combined marker panel of gut bacteria, blood metabolites, and clinical indices could distinguish the EC patients under lean and overweight conditions from normal subjects with high accuracy in both discovery and validation sets. In addition, the alteration of tumor microenvironment metabolism of EC was characterized by imaging mass microscopy. Spatial visualization of fatty acids showed that C16:1 and C18:1 obviously accumulate in tumor tissue, and C16:1 may promote EC cell invasion and metastasis through mTOR signaling. The aberrant fecal microbiome, more specifically, Ruminococcus sp. N15.MGS-57 and spatially distributed C16:1 in EC tissues, can be used as a biomarker of clinical features and outcomes and provide a new therapeutic target for clinical treatment. IMPORTANCE A growing number of studies have shown the connection between gut microbiota, obesity, and cancer. However, to our knowledge, the association between gut microbiota and endometrial cancer progression in humans has not been studied. We recruited EC and control individuals as research participants and further subgrouped subjects by body mass index to examine the association between gut microbiota, metabolites, and clinical indices. The higher richness of Ruminococcus sp. N15.MGS-57 in EC subjects was not only positively associated with blood C16:1 but also negatively correlated with betalain and indole alkaloid biosynthesis. Spatial visualization of fatty acids by imaging mass microscopy showed that C16:1 obviously accumulates in tumor tissue, and C16:1 may promote the EC cell invasion and metastasis through mTOR signaling. The aberrant fecal microbiome, more specifically, Ruminococcus sp. N15.MGS-57 and spatially distributed C16:1, can be used as a biomarker of clinical features and outcomes and provide a new therapeutic target for clinical treatment.

The Role of Branched-Chain Amino Acids and Branched-Chain α-Keto Acid Dehydrogenase Kinase in Metabolic Disorders.

Branched-chain amino acids (BCAAs), composed of leucine, isoleucine, and valine, are important essential amino acids in human physiology. Decades of studies have revealed their roles in protein synthesis, regulating neurotransmitter synthesis, and the mechanistic target of rapamycin (mTOR). BCAAs are found to be related to many metabolic disorders, such as insulin resistance, obesity, and heart failure. Also, many diseases are related to the alteration of the BCAA catabolism enzyme branched-chain α-keto acid dehydrogenase kinase (BCKDK), including maple syrup urine disease, human autism with epilepsy, and so on. In this review, diseases and the corresponding therapies are discussed after the introduction of the catabolism and detection methods of BCAAs and BCKDK. Also, the interaction between microbiota and BCAAs is highlighted.

Effectiveness of preoperative shaving and postoperative shampooing on the infection rate in neurosurgery patients: A meta-analysis.

OBJECTIVE: To evaluate the effectiveness of preoperative shaving and postoperative shampooing on the infection rate in neurosurgery. DESIGN: Meta-analysis. DATA SOURCE: We conducted a search of the Embase, CINAHL, Scopus and PubMed databases up until February 1, 2022. Comparative studies were included. No language restrictions were applied. REVIEW METHODS: Original articles that compared the infection rate of patients who had their hair shaved before neurosurgery to the infection rate of unshaven patients were included. Original articles comparing the infection rates of patients whose hair was early postoperative shampooing versus patients whose hair was not shampooed after neurosurgery were also included. The risk of bias was also evaluated using the Newcastle-Ottawa quality assessment scale by two authors independently. The meta-analyses were performed using Review Manager software (RevMan 5.3; Cochrane Collaboration). The odds ratios (ORs) and 95% confidence intervals (CIs) were assessed for dichotomous data (infection rate). The heterogeneity of the included studies was assessed using the I2 statistic (ranging from 0 to 100%). RESULTS: A total of 3451 studies were identified by searching the PubMed, Scopus, CINAHL and Embase databases. Fourteen studies met the inclusion criteria, however two studies did not provide data suitable for meta-analysis. Twelve studies were included in the review. Two historical control studies, four prospective studies, one clinical trial and five retrospective studies were identified. There were 4583 patients whose hair was not shaved and 4295 patients whose hair was shaved. Among them, there were 3874 patients whose hair was unshaved and was early postoperative shampooing. No significant difference in the infection rate was found between the unshaved group and shaved group (OR: 0.86, 95% CI [0.62, 1.19], P = 0.85, I2 = 0%). A significant difference in the infection rates in shunt surgery patients was found between the unshaved group and shaved group (OR: 0.43, 95% CI [0.19, 0.99], P = 0.89, I2 = 0%). No significant difference was found between the unshaved with early shampooing group and the shaved group (OR: 0.82, 95% CI [0.48, 1.41], P = 0.80, I2 = 0%). CONCLUSION: Hair preservation before neurosurgery and early shampooing after neurosurgery did not increase the infection rate.