Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

[Improvement of the mastication function of orthodontics combined with restoration in the treatment of deep overbite with severe lower anterior teeth attrition].

PURPOSE: To observe the effect of orthodontics combined with restoration on masticatory function in deep overbite patients with severe lower anterior teeth attrition. METHODS: From January 2018 to January 2022, a total of 164 deep overbite patients with severe lower anterior teeth attrition were collected and divided into two groups according to different treatment plans: control group(72 patients, with restoration treatment) and experimental group(92 patients, with orthodontics combined with restoration treatment). The chewing efficiency of the two groups was evaluated, temporomandibular joint dysfunction index (DI), muscle palpation index (PI) and cranio-mandibular index (CMI) were calculated. The satisfaction with facial esthetic, the Chinese version of Oral Health Impact Scale-14(OHIP-14) and the repair satisfaction score were evaluated, the occurrence of adverse events between the two groups was compared. SPSS 23.0 software package was used for statistical analysis. RESULTS: After treatment, the chewing efficiency of the experimental group was significantly improved compared to the control group, while the DI, PI, and CMI were significantly reduced compared to the control group(P＜0.05). Compared with the control group, the satisfaction degree with facial esthetic and restoration in the experimental group was significantly higher, while the OHIP-14 score was significantly lower after treatment(P＜0.05). The incidence of adverse events in the experimental group was significantly decreased compared with the control group (6.52% vs 25.00%, P＜0.05). CONCLUSIONS: Combination of orthodontics and restoration treatment can enhance the effectiveness of restoration treatment for deep overbite with severe lower anterior teeth attrition, improve the mastication function and temporomandibular joint balance,satisfaction and quality of life of patients, as well as reduce the risk of adverse events.

The association between the dietary inflammatory index and allergic rhinitis: a case-control study.

Background and objective: Allergic rhinitis (AR) is a common chronic inflammatory disease that significantly impacts the quality of life of patients. However, there is limited research on the relationship between the Dietary Inflammatory Index (DII) and the risk of AR. Our study aimed to assess the association between DII and AR in a sample of adults from North China. Methods: In a case-control study, we selected 166 cases of AR and 166 age- and gender-matched controls. Dietary intake was assessed using a validated food frequency questionnaire. The energy-adjusted DII (E-DII) scores were calculated based on the quantity of diet components with inflammatory or anti-inflammatory potential. We used conditional logistic regression models to examine the association between E-DII and AR. Results: Our findings indicate a positive correlation between E-DII and AR risk. After controlling for confounders, individuals in the highest E-DII tertile exhibited a 4.41-fold increased risk of AR compared to those in the lowest tertile (OR 4.41, 95% CI 2.31-8.41). Additionally, stratified analysis showed that E-DII was positively associated with AR subtype (seasonal vs. perennial), duration (≤6 years vs. >6 years), severity (mild vs. moderate-severe), and onset time (intermittent vs. persistent). Furthermore, individuals in the highest E-DII tertile had higher intake of total fat, SFA, PUFAs, and n-6 PUFAs. Conclusion: In conclusion, we realized that there is a positive association between the E-DII score and AR. The consumption of diets abundant in anti-inflammatory nutrients and low in pro-inflammatory nutrient contents is recommended as a preventative strategy against AR.

Values of a novel comprehensive prognostic nutritional index (FIDA) in the prognosis of non-small cell lung cancer.

Background: This study focuses on determining the prognostic and predictive value of the comprehensive prognostic nutrition index (FIDA) in individuals undergoing treatment for Non-Small-Cell Lung Carcinoma (NSCLC). Methods: This retrospective analysis encompassed 474 of NSCLC patients treated from January 2010 through December 2019. Employing the Lasso-COX regression approach, eight blood parameters were identified as significant prognostic indicators. These parameters contributed to the formulation of the comprehensive prognostic nutrition index FIDA. Utilizing X-tile software, the patient cohort was categorized into either a high or low FIDA group based on an established optimal threshold. The cohort was then randomly segmented into a training set and a validation set using SPSS software. Subsequent steps involved conducting univariate and multivariate regression analyze to develop a prognostic nomogram. The effectiveness of this nomogram was evaluated by calculating the AUC. Results: Analysis of survival curves for both the training and validation sets revealed a poorer prognosis in the high FIDA group compared to the low FIDA group. This trend persisted across various subgroups, including gender, age, and smoking history, with a statistical significance (p<0.05). Time-dependent ROC and diagnostic ROC analyses affirmed that FIDA serves as an effective diagnostic and prognostic marker in NSCLC. Moreover, Cox regression multivariate analysis established FIDA as an independent prognostic factor for NSCLC. The prognostic nomogram, integrating FIDA and clinical data, demonstrated substantial prognostic utility and outperformed the traditional TNM staging systemin predicting overall survival (OS). Conclusion: FIDA emerges as a dependable predictor of outcomes for patients with NSCLC. It offers a practical, cost-effective tool for prognostication in regular clinical applications.

Sex differences in PD-L1-induced analgesia in paclitaxel-induced peripheral neuropathy mice depend on TRPV1-based inhibition of CGRP.

AIMS: Paclitaxel (PTX) is extensively utilized in the management of diverse solid tumors, frequently resulting in paclitaxel-induced peripheral neuropathy (PIPN). The present study aimed to investigate sex differences in the behavioral manifestations and underlying pathogenesis of PIPN and search for clinically efficacious interventions. METHODS: Male and female C57BL/6 mice (5-6 weeks and 12 months, weighing 18-30 g) were intraperitoneally (i.p.) administered paclitaxel diluted in saline (NaCl 0.9%) at a dose of 2 mg/kg every other day for a total of 4 injections. Von Frey and hot plate tests were performed before and after administration to confirm the successful establishment of the PIPN model and also to evaluate the pain of PIPN and the analgesic effect of PD-L1. On day 14 after PTX administration, PD-L1 protein (10 ng/pc) was injected into the PIPN via the intrathecal (i.t.) route. To knock down TRPV1 in the spinal cord, adeno-associated virus 9 (AAV9)-Trpv1-RNAi (5 µL, 1 × 1013 vg/mL) was slowly injected via the i.t. route. Four weeks after AAV9 delivery, the downregulation of TRPV1 expression was verified by immunofluorescence staining and Western blotting. The levels of PD-L1, TRPV1 and CGRP were measured via Western blotting, RT-PCR, and immunofluorescence staining. The levels of TNF-α and IL-1ß were measured via RT-PCR. RESULTS: TRPV1 and CGRP protein and mRNA levels were higher in the spinal cords of control female mice than in those of control male mice. PTX-induced nociceptive behaviors in female PIPN mice were greater than those in male PIPN mice, as indicated by increased expression of TRPV1 and CGRP. The analgesic effects of PD-L1 on mechanical hyperalgesia and thermal sensitivity were significantly greater in female mice than in male mice, with calculated relative therapeutic levels increasing by approximately 2.717-fold and 2.303-fold, respectively. PD-L1 and CGRP were partly co-localized with TRPV1 in the dorsal horn of the mouse spinal cord. The analgesic effect of PD-L1 in PIPN mice was observed to be mediated through the downregulation of TRPV1 and CGRP expression following AAV9-mediated spinal cord specific decreased TRPV1 expression. CONCLUSIONS: PTX-induced nociceptive behaviors and the analgesic effect of PD-L1 in PIPN mice were sexually dimorphic, highlighting the significance of incorporating sex as a crucial biological factor in forthcoming mechanistic studies of PIPN and providing insights for potential sex-specific therapeutic approaches.

Elongatibacter sediminis gen. nov., sp. nov., isolated from intertidal sediment, and genomic comparison with all genera in the family Wenzhouxiangellaceae.

A novel slightly halophilic, aerobic, and Gram-stain-negative strain, designated as CH-27T, was isolated during a bacterial resource investigation of intertidal sediment collected from Xiaoshi Island in Weihai, PR China. Cells of strain CH-27T were rod-shaped with widths of 0.3-0.6 µm and lengths of 2.0-11.0 µm. Strain CH-27T grew optimally at 37 °C, pH 7.0 and with 2.0 % (w/v) NaCl. Catalase activity was weakly positive and oxidase activity was positive. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CH-27T was most related to Marinihelvus fidelis KCTC 92639T (93.6 %), followed by Wenzhouxiangella marina MCCC 1K00261T (92.0 %). Based on genome comparisons between strain CH-27T and M. fidelis KCTC 92639T, the average amino acid identity was 63.6 % and the percentage of conserved proteins was 48.3 %. The major cellular fatty acid of strain CH-27T (≥10 %) was iso-C15 : 0 and the sole respiratory quinone was quinone-8. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, and aminophospholipid. The DNA G+C content was 62.7 mol%. Based on comprehensive analysis of its phylogenetic, physiological, biochemical, and chemotaxonomic characteristics, strain CH-27T represents a novel species in a novel genus, for which the name Elongatibacter sediminis gen. nov., sp.nov. is proposed. The type strain is CH-27T (=MCCC 1H00480T=KCTC 8011T).

Carotid artery transplantation of brain endothelial cells enhances neuroprotection and neurorepair in ischaemic stroke rats.

Brain microvascular endothelial cells (BMECs), an important component of the neurovascular unit, can promote angiogenesis and synaptic formation in ischaemic mice after brain parenchyma transplantation. Since the therapeutic efficacy of cell-based therapies depends on the extent of transplanted cell residence in the target tissue and cell migration ability, the delivery route has become a hot research topic. In this study, we investigated the effects of carotid artery transplantation of BMECs on neuronal injury, neurorepair, and neurological dysfunction in rats after cerebral ischaemic attack. Purified passage 1 endothelial cells (P1-BMECs) were prepared from mouse brain tissue. Adult rats were subjected to transient middle cerebral artery occlusion (MCAO) for 30 min. Then, the rats were treated with 5 × 105 P1-BMECs through carotid artery infusion or tail vein injection. We observed that carotid artery transplantation of BMECs produced more potent neuroprotective effects than caudal injection in MCAO rats, including reducing infarct size and alleviating neurological deficits in behavioural tests. Carotid artery-transplanted BMECs displayed a wider distribution in the ischaemic rat brain. Immunostaining for endothelial progenitor cells and the mature endothelial cell markers CD34 and RECA-1 showed that carotid artery transplantation of BMECs significantly increased angiogenesis. Carotid artery transplantation of BMECs significantly increased the number of surviving neurons, decreased the cerebral infarction volume, and alleviated neurological deficits. In addition, we found that carotid artery transplantation of BMECs significantly enhanced ischaemia-induced hippocampal neurogenesis, as measured by doublecortin (DCX) and Ki67 double staining within 2 weeks after ischaemic injury. We conclude that carotid artery transplantation of BMECs can promote cerebral angiogenesis, neurogenesis, and neurological function recovery in adult rats after ischaemic stroke. Our results suggest that carotid injection of BMECs may be a promising new approach for treating acute brain injuries.

Continuous Rapid Fabrication of Ceramic Fiber Sponge Aerogels with High Thermomechanical Properties via a Green and Low-Cost Electrospinning Technique.

Ceramic aerogel is an appealing fireproof and heat-insulation material, but synchronously improving its mechanical and thermal properties is a challenge. Moreover, the expensive discontinuous processing techniques inhibit the large-scale fabrication of ceramic aerogels. Here, we propose a water-based electrospinning method, based on the hydrolysis and condensation reactions of ceramic precursor salts themselves, for the continuous and rapid (0.025 m3/min) fabrication of ceramic fiber sponge aerogels with dual micronano fiber networks, which show synchronous enhanced fireproof, thermal insulation, and resilience performance. The elastic ceramic micro/nano fiber sponge aerogels contain robust silica-based microfibers as a firm skeleton and alumina-based nanofibers as elastic thermal insulation filler. The sponges have a high porosity of >99.8%, a low mass density (6.21 mg/cm3), a small thermal conductivity (0.022 W/m·K), and a large compression strength (21.15 kPa at 80% strain). The ceramic fiber sponges can effectively prevent the propagation of thermal runaway when a lithium battery experiences catastrophic thermal shock (>1000 °C) in the power battery packs. The proposed strategy is feasible for low-cost and rapid synthesizing ceramic aerogels toward effective battery thermal management.

Dexamethasone alleviates etomidate-induced myoclonus by reversing the inhibition of excitatory amino acid transporters.

Background: Etomidate can induce myoclonus with an incidence of 50 ~ 85% during anesthesia induction. Dexamethasone, as a long-acting synthetic glucocorticoid, has neuroprotective effects. However, the effects of dexamethasone on the etomidate-induced myoclonus remain uncertain. Methods: Adult male Sprague-Dawley rats were randomly assigned to receive etomidate (1.5 mg/kg) plus dexamethasone (4 mg/kg) (etomidate plus dexamethasone group) or etomidate (1.5 mg/kg) plus the same volume of normal saline (NS) (etomidate plus NS group). The mean behavioral scores, local field potentials and muscular tension were recorded to explore the effects of dexamethasone on etomidate-induced myoclonus. Liquid chromatography coupled with tandem mass spectrometric system (LC-MS/MS), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting were applied to analyze the levels of glutamate and γ-aminobutyric acid (GABA), the mRNA and protein expression of excitatory amino acid transporters (EAATs), and plasma corticosterone levels at different time points after anesthesia. Results: Compared with the etomidate plus NS treatment, the etomidate plus dexamethasone treatment significantly decreased the mean behavioral score at 1, 3, 4, and 5 min after administration; the peak power spectral density (PSD) (p = 0.0197) in the analysis of ripple waves; and the glutamate level (p = 0.0139) in the neocortex. However, compared with etomidate plus NS, etomidate plus dexamethasone increased the expression of the neocortical proteins of EAAT1 (p = 0.0207) and EAAT2 (p = 0.0022) and aggravated the inhibition of corticosterone at 4 h (p = 0.0019), 5 h (p = 0.0041), and 6 h (p = 0.0009) after administration. Conclusion: Dexamethasone can attenuate the myoclonus, inhibit the glutamate accumulation, and reverse the suppression of EAATs in the neocortex induced by etomidate following myoclonus, while conversely aggravating etomidate-induced adrenal suppression.

Reduction of relative intensity noise in a diamond Raman laser.

The relative intensity noise (RIN) characteristics of a continuous-wave diamond Raman laser are investigated for the first time. The results reveal the parasitic stimulated Brillouin scattering (SBS) that usually occurred with higher-order spatial modes in the diamond Raman resonator is a pivotal factor impacting the Raman longitudinal modes and deteriorating the RIN level. The diamond Raman laser automatically switches to single-longitudinal-mode operation and the RIN level is significantly decreased in the frequency range of 200 Hz to 1 MHz after the parasitic SBS is effectively suppressed through inserting a spatial aperture or a χ(2) nonlinear crystal into the cavity. Due to the introduction of additional nonlinear loss to the high intensity Raman fluctuations and the non-lasing spontaneous Raman modes, the χ(2) nonlinear crystal enables better performance in the RIN-level reduction compared to the spatial aperture which can only achieve SBS inhibition. The RIN reduction routes are well suited for various crystalline Raman media to achieve high power and low intensity noise laser at different wavelengths.

20 Watt single-frequency 509 nm laser by single-pass second harmonic generation in an LBO crystal.

High power 509 nm continuous-wave (CW) lasers have important applications in science and communication. Here we demonstrate a robust high-power single-frequency 509 nm laser system based on nonlinear phase demodulation technique and single-pass second harmonic generation (SHG) configuration. In experiments, the single-frequency fundamental wave at 1018 nm was linewidth-broadened by an electro-optical modulator and then amplified to 207 W in a ytterbium-doped fiber amplifier. In subsequent single-pass SHG stage, over 20 W CW single-frequency 509 nm laser was generated in a LiB3O5 crystal with a SHG efficiency of 9.7%. To the best of our knowledge, this is the highest reported power for CW single-frequency 509 nm laser, which could be used for advanced underwater optical communication and preparation of cesium Rydberg state.

ED50 and ED95 of Remimazolam Tosilate Combined with Different Doses of Fentanyl in Elderly Patients for Painless Gastroscopy.

Background: The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam tosilate in gastroscopy for elderly patients when co-administered with fentanyl remains unclear. Therefore, the primary objective of our research was to ascertain the median effective dose (ED50) and the 95% effective dose (ED95) of remimazolam tosilate in combination with various fentanyl dosages for elderly patients undergoing painless gastroscopy. Methods: Seventy-five patients aged ≥65 years and American Society of Anesthesiologists (ASA) class I-III were recruited to undergo elective painless gastroscopy. All patients were randomized assigned to group F1, group F2, and group F3, and were injected intravenously with different doses of fentanyl (0.5 ug/kg, 1 ug/kg, and 1.5 ug/kg) 3 minutes prior to the administration of remimazolam tosilate, respectively. The initial preset dose of remimazolam tosilate was 0.3 mg/kg in group F1, 0.2 mg/kg in group F2, 0.15 mg/kg in group F3. The dose gradient was 0.02 mg/kg per group according to the up-and-down sequential method. Probibt regression model was employed to determine the ED50 and ED95 of remimazolam tosilate. Results: The ED50 of remimazolam tosilate in group F3 was lower than that in group F1 and F2 (0.095 [0.088-0.108] mg/kg vs 0.162 [0.153-0.171] mg/kg; 0.258 [0.249-0.266] mg/kg, p < 0.05). The ED95 of remimazolam tosilate was 0.272 mg/kg (95% CI: 0.264-0.295 mg/kg) in group F1, 0.175 mg/kg (95% CI: 0.167-0.200 mg/kg) in group F2 and 0.109 mg/kg (95% CI: 0.101-0.135 mg/kg) in group F3. The total dosage of remimazolam tosilate decreased gradually with the increasing of fentanyl (p < 0.001). The frequency of injection pain was higher in group F1 compared to groups F2 and F3 (p < 0.05). The patients in group F3 had a lower incidence of hypotension than in groups F1 and F2 (p < 0.05). There was no respiratory depression, intraoperative consciousness, dizziness or delirium in the three groups. Conclusion: The concurrent use of fentanyl reduces the dosage of remimazolam tosilate required for sedative gastroscopy in elderly patients in a dose-dependent manner. Moreover, 1.5 ug/kg fentanyl combined with remimazolam tosilate may reduce the incidence of hypotension and injection pain. These findings should be confirmed in a large-scale study.

Unconventional Magnetic and Magneto-Transport Properties in Quasi-2D Ni0.28TaSeS Single Crystal.

Van der Waals (vdW) magnetic materials have broad application prospects in next-generation spintronics. Inserting magnetic elements into nonmagnetic vdW materials can introduce magnetism and enhance various transport properties. Herein, the unconventional magnetic and magneto-transport phenomena is reported in Ni0.28TaSeS crystal by intercalating Ni atoms into nonmagnetic 2H-TaSeS matrix. Magnetic characterization reveals a canted magnetic structure in Ni0.28TaSeS, which results in an antiferromagnetic (AFM) order along the c-axis and a ferromagnetic (FM) moment in the ab-plane. The presence of spin-flop (SF) behavior can also be attributed to the canted magnetic structure. Temperature-dependent resistivity exhibits a metallic behavior with an abrupt decrease corresponding to the magnetic transition. Magneto-transport measurements demonstrate a positive magnetoresistance (MR) with a plateau that is different from conventional magnetic materials. The field-dependent Hall signal exhibits nonlinear field dependence when the material is in magnetically ordered state. These unconventional magneto-transport behaviors are attributed to the field-induced formation of a complex spin texture in Ni0.28TaSeS. In addition, it further investigated the angle dependence of MR and observed an unusual fourfold anisotropic magnetoresistance (AMR) effect. This work inspires future research on spintronic devices utilizing magnetic atom-intercalated quasi-2D materials.

Ar/NH3 Plasma Etching of Cobalt-Nickel Selenide Microspheres Rich in Selenium Vacancies Wrapped with Nitrogen Doped Carbon Nanotubes as Highly Efficient Air Cathode Catalysts for Zinc-Air Batteries.

This work utilizes defect engineering, heterostructure, pyridine N-doping, and carbon supporting to enhance cobalt-nickel selenide microspheres' performance in the oxygen electrode reaction. Specifically, microspheres mainly composed of CoNiSe2 and Co9Se8 heterojunction rich in selenium vacancies (VSe·) wrapped with nitrogen-doped carbon nanotubes (p-CoNiSe/NCNT@CC) are prepared by Ar/NH3 radio frequency plasma etching technique. The synthesized p-CoNiSe/NCNT@CC shows high oxygen reduction reaction (ORR) performance (half-wave potential (E1/2) = 0.878 V and limiting current density (JL) = 21.88 mA cm-2). The JL exceeds the 20 wt% Pt/C (19.34 mA cm-2) and the E1/2 is close to the 20 wt% Pt/C (0.881 V). It also possesses excellent oxygen evolution reaction (OER) performance (overpotential of 324 mV@10 mA cm-2), which even exceeds that of the commercial RuO2 (427 mV@10 mA cm-2). The density functional theory calculation indicates that the enhancement of ORR performance is attributed to the synergistic effect of plasma-induced VSe· and the CoNiSe2-Co9Se8 heterojunction. The p-CoNiSe/NCNT@CC electrode assembled Zinc-air batteries (ZABs) show a peak power density of 138.29 mW cm-2, outperforming the 20 wt% Pt/C+RuO2 (73.9 mW cm-2) and other recently reported catalysts. Furthermore, all-solid-state ZAB delivers a high peak power density of 64.83 mW cm-2 and ultra-robust cycling stability even under bending.

SERPINC1, a new prognostic predictor of colon cancer, promote colon cancer progression through EMT.

BACKGROUND: Liver metastasis of CRC is still the main cause of poor prognosis in patients with CRC. Previous studies have suggested that serpin family C member 1(SERPINC1) is involved in the development of a variety of tumours, but its effect on colorectal cancer progression has been poorly elucidated. METHODS: Based on the GEO database, this study identifies the core gene SERPINC1 associated with liver metastasis in CRC. We used transcriptomic data and immunohistochemical staining to explore the expression of SERPINC1 in normal, cancer, and liver metastases tissue from CRC patients. Clinical data obtained from our hospital were used to explore the impact of SERPINC1 on the prognosis of colon cancer patients. Mechanistically, the biological functions exerted by SERPINC1 in CRC were predicted by bioinformatics, and the results were validated by the results of the experiments in vitro. Cell lines with knockdown of SERPINC1 were performed a series assay such as trans well, CCK-8 and colony formation assay to explore the relationship between SERPINC1 and proliferation and metastasis of CRC cells. Finally, the effect of SERPINC1 on the sensitivity of colon cancer patients to immune checkpoint therapy was evaluated. RESULTS: In CRC liver metastatic tissues, we found significantly high expression of SERPINC1. Briefly, 212 CRC cohorts showed that SERPINC1 was significantly associated with TNM stage and plasma CA19-9 and CEA in CRC patients. Univariate and multivariate Cox demonstrated that SERPINC1 was significantly associated with 5-year survival after radical surgery for colorectal cancer (p < 0.001). Bioinformatics predicted that SERPINC1 affects metastasis of colon cancer through epithelial-mesenchymal transition (EMT). Colony formation assay and CCK-8 assay showed that SERPINC1 promotes malignant proliferation of CRC cells, trans well assay showed that SERPINC1 promotes distant migratory behaviour of CRC cells and protein blotting assay showed that SERPINC1 may promote migration by promoting the TGF-ß1-mediated EMT of CRC cells. In addition, several immunotherapy cohorts also reflected that the expression of SERPINC1 reduced the sensitivity of CRC patients to immune checkpoint therapy. CONCLUSION: Our study identified SERPINC1 as a novel liver metastasis-associated gene in CRC. Targeting SERPINC1 may be a novel therapeutic strategy for patients with liver metastases from CRC.

Associations between metabolic dysfunction-associated fatty liver disease and atherosclerotic cardiovascular disease.

Non-alcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome and remains a major global health burden. The increased prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide has contributed to the rising incidence of NAFLD. It is widely believed that atherosclerotic cardiovascular disease (ASCVD) is associated with NAFLD. In the past decade, the clinical implications of NAFLD have gone beyond liver-related morbidity and mortality, with a majority of patient deaths attributed to malignancy, coronary heart disease (CHD), and other cardiovascular (CVD) complications. To better define fatty liver disease associated with metabolic disorders, experts proposed a new term in 2020 - metabolic dysfunction associated with fatty liver disease (MAFLD). Along with this new designation, updated diagnostic criteria were introduced, resulting in some differentiation between NAFLD and MAFLD patient populations, although there is overlap. The aim of this review is to explore the relationship between MAFLD and ASCVD based on the new definitions and diagnostic criteria, while briefly discussing potential mechanisms underlying cardiovascular disease in patients with MAFLD.

Pan-drug resistance and hypervirulence in a human fungal pathogen are enabled by mutagenesis induced by mammalian body temperature.

The continuing emergence of invasive fungal pathogens poses an increasing threat to public health. Here, through the China Hospital Invasive Fungal Surveillance Net programme, we identified two independent cases of human infection with a previously undescribed invasive fungal pathogen, Rhodosporidiobolus fluvialis, from a genus in which many species are highly resistant to fluconazole and caspofungin. We demonstrate that R. fluvialis can undergo yeast-to-pseudohyphal transition and that pseudohyphal growth enhances its virulence, revealed by the development of a mouse model. Furthermore, we show that mouse infection or mammalian body temperature induces its mutagenesis, allowing the emergence of hypervirulent mutants favouring pseudohyphal growth. Temperature-induced mutagenesis can also elicit the development of pan-resistance to three of the most commonly used first-line antifungals (fluconazole, caspofungin and amphotericin B) in different Rhodosporidiobolus species. Furthermore, polymyxin B was found to exhibit potent activity against the pan-resistant Rhodosporidiobolus mutants. Collectively, by identifying and characterizing a fungal pathogen in the drug-resistant genus Rhodosporidiobolus, we provide evidence that temperature-dependent mutagenesis can enable the development of pan-drug resistance and hypervirulence in fungi, and support the idea that global warming can promote the evolution of new fungal pathogens.

Evaluation of provincial forest ecological security and analysis of the driving factors in China via the GWR model.

Economic and social factors pose an enormous threat to forest ecological security, which in turn affects the development of ecological civilization. This paper applies a geographically weighted regression model to study the impact of urbanization, industrial structure, and foreign direct investment on forest ecological security of 30 provinces in 2013 and 2018 and reveals the spatial differences of various influencing factors in different provinces. First, the overall forest ecological security in China is at an average level, with slight improvement. Second, urbanization has the greatest impact on forest ecological security in all provinces, which shows a rising trend. Third, the positive impact of industrial structure on forest ecological security has improved. Fourth, in 2013, FDI (foreign direct investment) had a negative correlation with forest ecological security. In 2018, FDI had a positive impact on the forest ecological security index of 16 provinces, while it had a negative correlation in other provinces. Therefore, it is necessary to formulate a coordinated security improvement plan for neighboring provinces. The government should promote rural revitalization, plan the layout of cities rationally, increase the proportion of tertiary industry, appropriately raise access barriers to foreign investment and strengthen environmental supervision over existing foreign-invested enterprises.

Lung microbiota participated in fibrous microplastics (MPs) aggravating OVA-induced asthma disease in mice.

Environmental pollution is one of the risk factors for asthma. Currently, whether micro-plastics could aggravate asthma, is still unclear. In the air, fibrous MPs are the predominant shape. Since fibrous micro-plastics are reported to be detected in the lower respiratory tract and other body parts, the relationship of fibrous MP and asthma, as well as the potential mechanism is not well investigated. In this study, we produced fibrous MPs, whose lengths and widths were in accordance with the natural environment, and further, investigated the potential adverse effect of which on the asthma in a OVA (ovalbumin)-induced mice model, aiming at exploring the true life hazard of MP to the respiratory system. Following nasal exposure to fibrous MPs, the airway inflammation, mucus hypersecretion and fibrosis were aggravated in asthmatic mice. Fibrous MPs exposure also significantly increased the levels of total IgE, and, cardinal Th2 and Th1 pro-inflammatory cytokines participated in the etiopathogenesis of allergic airway inflammation. In addition, MP fibers exposure induced lung epithelial cells apoptosis, disruption of epithelial barrier integrity and activation of NLRP3 related signaling pathways. Moreover, fibrous MPs significantly altered the bacterial composition at the genus level. Compared to the control group, the relative abundance of Escherichia-Shigella and Uncultured were decreased to 4.47% and 0.15% in OVA group, while Blautia and Prevotella were elevated to 4.96% and 2.94%. For the OVA + MPs group, the relative abundance of Blautia and Uncultured were decreased to 2.27% and 0.006%, while Prevotella was increased to 3.05%. Our study highlights the detrimental effect of fibrous MPs on asthmatic population and facilitates an indication of the latent mechanisms of fibrous MPs induced airway pathology.