Altered metabolome and microbiome associated with compromised intestinal barrier induced hepatic lipid metabolic disorder in mice after subacute and subchronic ozone exposure.

Exposure to ozone has been associated with metabolic disorders in humans, but the underlying mechanism remains unclear. In this study, the role of the gut-liver axis and the potential mechanism behind the metabolic disorder were investigated by histological examination, microbiome and metabolome approaches in mice during the subacute (4-week) and subchronic (12-week) exposure to 0.5 ppm and 2.5 ppm ozone. Ozone exposure resulted in slowed weight gain and reduced hepatic lipid contents in a dose-dependent manner. After exposure to ozone, the number of intestinal goblet cells decreased, while the number of tuft cells increased. Tight junction protein zonula occludens-1 (ZO-1) was significantly downregulated, and the apoptosis of epithelial cells increased with compensatory proliferation, indicating a compromised chemical and physical layer of the intestinal barrier. The hepatic and cecal metabolic profiles were altered, primarily related to lipid metabolism and oxidative stress. The abundance of Muribaculaceae increased dose-dependently in both colon and cecum, and was associated with the decrease of metabolites such as bile acids, betaine, and L-carnitine, which subsequently disrupted the intestinal barrier and lipid metabolism. Overall, this study found that subacute and subchronic exposure to ozone induced metabolic disorder via disturbing the gut-liver axis, especially the intestinal barrier. These findings provide new mechanistic understanding of the health risks associated with environmental ozone exposure and other oxidative stressors.

Study protocol of short-course radiotherapy combined with CAPOX and PD-1 inhibitor for locally advanced colon cancer: a randomised, prospective, multicentre, phase II trial (TORCH-C).

INTRODUCTION: The preliminary result of the TORCH trial has shown a promising complete response (CR) for managing locally advanced rectal cancer with neoadjuvant short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor. For locally advanced colon cancer (LACC) with bulky nodal disease and/or clinically T4, neoadjuvant chemotherapy followed by colectomy with en bloc removal of regional lymph nodes is the suggested treatment. However, the CR rate is less than 5%. TORCH-C will aim to investigate neoadjuvant SCRT combined with chemotherapy and PD-1 inhibitor in LACC. METHODS AND ANALYSIS: TORCH-C is a randomised, prospective, multicentre, double-arm, open, phase II trial of SCRT combined with chemotherapy and immunotherapy in LACC with microsatellite stable (MSS) patients and cT4 or bulky nodes. Eligible patients will be identified by the multidisciplinary team. 120 patients will be randomised 1:1 to the intervention or control arm. The patients in the control arm will receive four cycles of capecitabine plus oxaliplatin (CAPOX). The patients in the intervention arm will receive SCRT, followed by four cycles of CAPOX and PD-1 inhibitor (serplulimab). Both arms will receive curative surgery, followed by four cycles of CAPOX. The primary endpoint is pathological complete regression.TORCH-C (TORCH-colon) trial aims to investigate whether the combination of immunotherapy and chemoradiotherapy improves the treatment effect in LACC with MSS. TORCH-C will establish the TORCH platform, a key part of our long-term strategy to develop neoadjuvant treatment for colorectal cancer. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (approval number: 2211265-12). TRIAL REGISTRATION NUMBER: NCT05732493.

Engineering of Ultra-Thin Layer of MIL-125(Ti) Nanosheet\Zn-Tetracarboxy-Phthalocyanine S-Scheme Heterojunction as Photocatalytic CO2 Reduction Catalyst.

Metal-organic frameworks (MOFs) with ultrathin 2D structure have attracted remarkable attention in photocatalytic application owing to the accessibility of abundant active sites on the surface. But high charge recombination results in poor photocatalytic activity. Herein, the synthesis of ultrathin MIL-125(Ti) nanosheets is reported with a thickness of 1.3 nm through a simple chemical reaction route of precursor solution aging and subsequent solvothermal process for photocatalytic CO2 production. The maximal CO evolution rate achieves 200.8 µmol g-1 h-1 , which is prominently higher than that (78.6 µmol g-1 h-1 ) of the bulk MIL-125(Ti) counterpart. Furthermore, the structurally stable Zn (II) tetracarboxy phthalocyanine (ZnTcPc) molecules assembly on ultrathin MIL-125(Ti) nanosheet (NS) to form MIL-125(Ti) NS\ZnTcPc S-scheme heterojunction through the strong interaction between the Ti3+ in MIL-125(Ti) and the COOH in ZnTcPc. The introduction of ZnTcPc greatly extends light absorption range and increases charge separation rate. The experimental and density functional theory calculation results validate that the MIL-125(Ti) NS\ZnTcPc S-scheme heterojunction can favor CO2 adsorption and effectively depress the formation energy of the intermediates, achieving a high CO evolution rate of 450.8 µmol g-1 h-1 . This work provides a strategy of engineering 2D MOF-based heterostructure systems for photocatalytic application.

Meta analysis of ovulation induction effect and pregnancy outcome of acupuncture & moxibustion combined with clomiphene in patients with polycystic ovary syndrome.

Objective: Using Mesh Meta Analysis to evaluate the efficacy of Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene for treating Polycystic Ovary Syndrome (PCOS), in order to provide evidence-based medical evidence for whether to recommend Acupuncture & Moxibustion or Combine western medicine to treat PCOS. Methods: Eight databases including The Cochrane Library, Pubmed, Embase, Web of Science, CNKI, Wanfang Date, VIP and CBM were searched by computer. The included research period is from the establishment of the database to May 2023, which concerned with randomized controlled trials involving Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene on ovulation induction and pregnancy outcome in patients with PCOS. The duration of the research paper is from 2016 to 2023.The inclusion criteria refer to the Rotterdam standards issued by the European Center for Human Reproduction and Embryology and the American Society of Reproductive Medicine in January 2003, or the Expert Consensus on the Diagnosis and Treatment of Polycystic Ovarian Syndrome by the Endocrinology Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association. Simultaneously exclude related diseases, repetitive literature, as well as literature with incomplete abstract information and no original data provided. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias included in the study, using Stata17.0 software for a mesh meta-analysis. Results: Six randomized controlled trials were included, covering 1410 PCOS patients. Three interventions included Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene. Mesh Meta Analysis showed that in terms of improving ovulation rate, there was no statistical difference between Acupuncture & Moxibustion (A), Clomiphene (B), Clomiphene combined with Acupuncture & Moxibustion (C) (P>0.05).Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=0.15,95% CI (-0.51,0.80)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.60,95% CI (0.97,2.23)], Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.45,95% CI (0.91,1.99)]. In terms of pregnancy outcome, the difference between the three intervention methods was statistically significant (P<0.05). Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=-0.80,95% CI (-1.84,0.23)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=0.29,95% CI (-0.73,1.30)], and Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.09,95% CI (0.39,1.79)], The order of pregnancy rate from high to low is Acupuncture & Moxibustion combined with Clomiphene (C), Acupuncture & Moxibustion (A), Clomiphene (C).In terms of influencing endometrial thickness, the difference between the three intervention methods was statistically significant (P<0.05). Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=-0.84,95% CI (-1.87,0.19)], Acupuncture & Moxibustion (A) versus Acupuncture & Moxibustion combined with Clomiphene (C) [MD=0.26,95% CI (-1.01,1.53)], Clomiphene (B) versus Acupuncture & Moxibustion combined with Clomiphene (C) [MD=1.10,95% CI (0.36,1.84)], Acupuncture & Moxibustion combined with Clomiphene (C) has the best effect on improving endometrial thickness. In subgroup analysis, the effect of Acupuncture & Moxibustion treatment frequency on ovulation rate and pregnancy rate was not statistically significant. The combination of Acupuncture & Moxibustion, Electroacupuncture and warm Acupuncture & Moxibustion has no effect on the pregnancy rate, but the combination of Electroacupuncture and Clomiphene has the best effect on improving the ovulation rate. In the observation of adverse reactions, compared with clomiphene alone, Acupuncture & Moxibustion combined with Clomiphene can reduce the occurrence of Luteinized Unruptured Follicle Syndrome (LUFS) and Ovarian Hyperstimulation Syndrome (OHSS), and reduce the occurrence of physical adverse reactions such as nausea, vomiting, headache and dermatitis. Conclusion: Acupuncture & Moxibustion is effective in improving the ovulation promoting effect and pregnancy outcome of PCOS patients. The ovulation promoting effect of Acupuncture & Moxibustion or combined with Clomiphene is similar to that of Clomiphene alone, but Acupuncture & Moxibustion combined with Clomiphene has more advantages in improving the pregnancy rate of PCOS, and it also can reduce the adverse reactions of Clomiphene alone. Acupuncture & Moxibustion can be used as a recommended treatment for PCOS. More cases should also be included in the subgroup analysis to study the impact of Acupuncture & Moxibustion programs on clinical efficacy and further optimize the Acupuncture & Moxibustion treatment program. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier (CRD42023433057).

TORCH-R trial protocol: hypofractionated radiotherapy combined with chemotherapy and toripalimab for locally recurrent rectal cancer: a prospective, single-arm, two-cohort, phase II trial.

For patients with locally recurrent rectal cancer (LRRC), the response rate to chemoradiotherapy is 40%-50%. Additionally, only approximately 40%-50% of patients with recurrent rectal cancer are able to undergo R0 resection. Recent studies in locally advanced rectal cancer (LARC) have shown promising synergistic effects when combining immunotherapy (PD-1/PD-L1 antibodies) with neoadjuvant chemoradiotherapy (nCRT). Therefore, incorporating immunotherapy into the treatment regimen for LRRC patients has the potential to further improve response rates and prognosis. To investigate this, the TORCH-R trial was conducted. This prospective, single-arm, two-cohort, phase II trial focuses on the use of hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients without or with oligometastases. The trial will include two cohorts: cohort A consists of rectal cancer patients who are treatment-naive for local recurrence, and cohort B includes patients with progressive disease after first-line chemotherapy. Cohort A and cohort B patients will receive 25-40 Gy/5 Fx irradiation or 15-30 Gy/5 Fx reirradiation for pelvic recurrence, respectively. Subsequently, they will undergo 18 weeks of chemotherapy, toripalimab, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles. Decisions regarding follow-up of complete response (CR), radical surgery, sustained treatment of non-resection, or exiting the trial are made by a multidisciplinary team (MDT). The primary endpoint of this study is the local objective response rate (ORR). The secondary endpoints include the extrapelvic response rate, duration of response, local recurrence R0 resection rate, progression-free survival (PFS), overall survival (OS), and safety and tolerability. Notably, this trial represents the first clinical exploration of inducing hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients. Clinical trial registration: https://clinicaltrials.gov/study/NCT05628038, identifier NCT05628038.

Combination of Backbone Rigidity and Richness in Aryl Structures Enables Direct Membrane Translocation of Polymer Scaffolds for Efficient Gene Delivery.

The development of cell-penetrating polymers with endocytosis-independent cell uptake pathways has emerged as a prominent strategy to enhance the transfection efficiency. Inspired by the rigid α-helical structure that endows polypeptides with cell-penetrating ability, we propose that a rigid backbone can facilitate the corresponding polymer vector's performance in gene delivery by bypassing the difficult endosomal escape process. Meanwhile, the installation of aromatic domains, as a way to promote gene transfection efficiency, is employed through the construction of a poly(benzyl ether) (PBE)-based scaffold in this work. We demonstrate that the direct membrane translocation capability of the synthesized PBE contributes to its enhanced transfection performance and excellent biocompatibility profile, rendering the imidazolium-functionalized PBE scaffold with higher activity and biocompatibility. Molecular details of the PBE-lipid interaction are also revealed in molecular dynamics simulations, indicating the important roles of individual structural elements on the polymeric scaffold in the membrane penetration process.

Short-course radiotherapy combined with chemotherapy and PD-1 inhibitor in low-lying early rectal cancer: study protocol for a single-arm, multicentre, prospective, phase II trial (TORCH-E).

INTRODUCTION: Current standard treatment for patients with early rectal cancer is radical surgical resection. Although radical surgery provides effective local tumour control, it also increases the mortality risk and considerable adverse effects, including bowel, bladder, sexual dysfunction and loss of anal function, especially in patients with low-lying rectal cancer. Recent studies have shown promising synergistic effects of the combination of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors and radiotherapy in improving tumour regression. For patients who reach a clinical complete response (cCR) after neoadjuvant therapy, a 'Watch & Wait' (W&W) approach can be adopted to preserve anorectal function and improve quality of life. Thus, this study aims to explore the efficacy and safety of radiotherapy combined with chemotherapy and PD-1 antibody in patients with low early rectal cancer. METHODS AND ANALYSIS: TORCH-E study is designed as a multicentre, prospective, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor in patients with cT1-3bN0M0 low rectal cancer. The trial was initiated in December 2022 and is currently recruiting patients, with an anticipated completion of participant enrolment by June of the following year. The enrolled 34 patients will receive SCRT (25 Gy/5 Fx), followed by four cycles of capecitabine plus oxaliplatin chemotherapy and PD-1 antibody (toripalimab) and finally receive surgery or the W&W strategy. The primary endpoint is the complete response (CR) rate, that is, the rate of pathological complete response (pCR) plus cCR. The secondary endpoints include organ preservation rate, 3-year local recurrence-free survival rate, 3-year disease-free survival rate, 3-year overall survival rate, grade 3-4 adverse effects rate and patients' quality of life. ETHICS AND DISSEMINATION: This trial has been approved by the Ethics Committee of Fudan University Shanghai Cancer Center. Trial results will be disseminated via peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05555888 (ClinicalTrials.gov).

Regorafenib alone or in combination with high/low-dose radiotherapy plus toripalimab as third-line treatment in patients with metastatic colorectal cancer: protocol for a prospective, randomized, controlled phase II clinical trial (SLOT).

Combination strategies to improve immunotherapy response in microsatellite stable metastatic colorectal cancer (MSS mCRC) remain an unmet need. Several single-arm clinical trials have shown promising synergistic effects between regorafenib and ICIs; however, some contradictory results have also been reported. Randomized controlled trials are needed to further validate the combination of regorafenib with ICIs. In addition, low-dose radiotherapy has been demonstrated to induce local immune responses by reprogramming the tumor microenvironment when combined with high-dose radiotherapy and ICIs. In this study, we designed a prospective, randomized, controlled phase II trial to investigate the efficacy and safety of regorafenib in combination with high/low-dose radiotherapy plus toripalimab in MSS mCRC compared to regorafenib alone. Patients with MSS metastatic adenocarcinoma of the colon or rectum will be enrolled and randomly assigned into two arms: a control arm and an experimental arm. Patients in the control arm will receive regorafenib monotherapy (120 mg once daily on days 1-21 of each 28 days cycle). Patients in the experimental arm will first receive one cycle of regorafenib (80 mg once daily on days 1-21 of each 28 days cycle) and toripalimab (240mg, q3w), followed by high-dose (4-8 fractions of 8-12Gy) and low-dose (1-10Gy at 0.5-2Gy/fraction) radiotherapy, and then continue regorafenib and toripalimab treatment. The primary endpoint is the objective response rate, and the secondary endpoints are disease control rate, duration of remission, median progress-free survival, median overall survival, and adverse events. Recruitment started in August 2023 and is ongoing. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05963490?cond=NCT05963490&rank=1, identifier NCT05963490.

RIFLE: a Phase II trial of stereotactic ablative radiotherapy combined with fruquintinib and tislelizumab in metastatic colorectal cancer.

Background: Currently, the prognosis for metastatic colorectal cancer (mCRC) still remains poor. The management of mCRC has become manifold because of the varied advances in the systemic and topical treatment approaches. For patients with limited number of metastases, radical local therapy plus systemic therapy can be a good choice to achieve long-term tumor control. In this study, we aimed to explore the efficacy and safety of the combination of fruquintinib, tislelizumab, and stereotactic ablative radiotherapy (SABR) in mCRC (RIFLE study). Methods: RIFLE was designed as a single-center, single-arm, prospective Phase II clinical trial. A total of 68 mCRC patients who have failed the first-line standard treatment will be recruited in the safety run-in phase (n = 6) and the expansion phase (n = 62), respectively. Eligible patients will receive SABR followed by fruquintinib (5 mg, d1-14, once every day) and tislelizumab (200 mg, d1, once every 3 weeks) within 2 weeks from completion of radiation. The expansion phase starts when the safety of the treatment is determined (dose limiting toxicity occur in no more than one-sixth of patients in the run-in phase). The primary end point is the objective response rate. The secondary end points include the disease control rate, duration of response, 3-year progression-free survival rate, 3-year overall survival rate, and toxicity. Conclusions: The results of this trial will provide a novel insight into SABR in combination with PD-1 antibody and vascular endothelial growth factor receptor inhibitor in the systematic treatment of metastatic colorectal cancer, which is expected to provide new therapeutic strategies and improve the prognosis for mCRC patients. Trial registration: NCT04948034 (ClinicalTrials.gov).

Bioavailability evaluation of epoxiconazole and difenoconazole in rice and the influence of dissolved organic matter in reducing uptake and translocation.

The aim of this study was to assess the bioavailability of epoxiconazole (EPO) and difenoconazole (DIF) in rice plants by evaluating their uptake, translocation, and accumulation. The results showed that the concentration of DIF in the roots was approximately three times higher than EPO, and both accumulated mainly in the roots. In addition, EPO continued to be transported from stems to leaves, causing a rise in its concentration in leaves. Contrastingly, only a minimal amount of DIF was transported to the leaves. This phenomenon is mainly governed by their differing octanol-water partition coefficient. The effects of dissolved organic carbon (DOC) on the accumulation of EPO and DIF in the roots were similar to those of the freely dissolved concentration measured by OECAMs. The concentrations of EPO and DIF in the roots and OECAMs consistently decreased with increasing DOC levels. Furthermore, a significant linear relationship was observed between the EPO and DIF concentrations in root and OECAMs. We also confirmed the accuracy and usefulness of the OECAMs method in predicting the bioavailability of EPO and DIF in rice roots. Therefore, OECAMs show good potential for use as a passive sampler to evaluate the bioavailability of EPO and DIF.

Bioavailability assessment of difenoconazole to earthworms (Eisenia fetida) in soil by oleic acid-embedded cellulose acetate membrane.

Passive sampling technology is widely used to evaluate the bioavailability of pollutants. However, relatively few studies have used passive sampling membranes (PSMs) to evaluate the environmental risks of pollutants in soil, particularly pesticides. Here, the bioavailability of difenoconazole to earthworms (Eisenia fetida) was evaluated using an oleic acid-embedded cellulose acetate membrane (OECAM) for the first time. Difenoconazole reached 94 % equilibrium (T94%) within 1 d in OECAM. For soil pore water, the freely dissolved concentration (Cfree) of difenoconazole was determined using OECAM (R2 = 0.969). In the soil system, a strong linear correlation between the difenoconazole concentration in OECAM and earthworms was observed (R2 = 0.913). The bioavailability of difenoconazole was affected by the soil type and biochar content. The higher the content of soil organic matter and biochar, the lower the concentration of difenoconazole in earthworms, OECAM, and soil pore water. The concentrations of difenoconazole in pore water, earthworms, and OECAM decreased by 65.3, 42.0, and 41.6 %, respectively, when 0.5 % biochar was added. Difenoconazole mainly enters OECAM and earthworms through passive diffusion with similar uptake pathways. Therefore, the bioavailability of difenoconazole to earthworms in different soils can be evaluated using the OECAM.

Long-term SARS-CoV-2 neutralizing antibody level prediction using multimodal deep learning: A prospective cohort study on longitudinal data in Wuhan, China.

The ongoing epidemic of SARS-CoV-2 is taking a substantial financial and health toll on people worldwide. Assessing the level and duration of SARS-CoV-2 neutralizing antibody (Nab) would provide key information for government to make sound healthcare policies. Assessed at 3-, 6-, 12-, and 18-month postdischarge, we described the temporal change of IgG levels in 450 individuals with moderate to critical COVID-19 infection. Moreover, a data imputation framework combined with a novel deep learning model was implemented to predict the long-term Nab and IgG levels in these patients. Demographic characteristics, inspection reports, and CT scans during hospitalization were used in this model. Interpretability of the model was further validated with Shapely Additive exPlanation (SHAP) and Gradient-weighted Class Activation Mapping (GradCAM). IgG levels peaked at 3 months and remained stable in 12 months postdischarge, followed by a significant decline in 18 months postdischarge. However, the Nab levels declined from 6 months postdischarge. By training on the cohort of 450 patients, our long-term antibody prediction (LTAP) model could predict long-term IgG levels with relatively high area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1-score, which far exceeds the performance achievable by commonly used models. Several prognostic factors including FDP levels, the percentages of T cells, B cells and natural killer cells, older age, sex, underlying diseases, and so forth, served as important indicators for IgG prediction. Based on these top 15 prognostic factors identified in IgG prediction, a simplified LTAP model for Nab level prediction was established and achieved an AUC of 0.828, which was 8.9% higher than MLP and 6.6% higher than LSTM. The close correlation between IgG and Nab levels making it possible to predict long-term Nab levels based on the factors selected by our LTAP model. Furthermore, our model identified that coagulation disorders and excessive immune response, which indicate disease severity, are closely related to the production of IgG and Nab. This universal model can be used as routine discharge tests to identify virus-infected individuals at risk for recurrent infection and determine the optimal timing of vaccination for general populations.

An armoured marine reptile from the Early Triassic of South China and its phylogenetic and evolutionary implications.

Sauropterygia was a taxonomically and ecomorphologically diverse clade of Mesozoic marine reptiles spanning the Early Triassic to the Late Cretaceous. Sauropterygians are traditionally divided into two groups representing two markedly different body plans - the short-necked, durophagous Placodontia and the long-necked Eosauropterygia - whereas Saurosphargidae, a small clade of armoured marine reptiles, is generally considered as the sauropterygian sister-group. However, the early evolutionary history of sauropterygians and their phylogenetic relationships with other groups within Diapsida are still incompletely understood. Here, we report a new saurosphargid from the Early Triassic (Olenekian) of South China - Prosaurosphargis yingzishanensis gen. et sp. nov. - representing the earliest known occurrence of the clade. An updated phylogenetic analysis focussing on the interrelationships among diapsid reptiles recovers saurosphargids as nested within sauropterygians, forming a clade with eosauropterygians to the exclusion of placodonts. Furthermore, a clade comprising Eusaurosphargis and Palatodonta is recovered as the sauropterygian sister-group within Sauropterygomorpha tax. nov. The phylogenetic position of several Early and Middle Triassic sauropterygians of previously uncertain phylogenetic affinity, such as Atopodentatus, Hanosaurus, Majiashanosaurus, and Corosaurus, is also clarified, elucidating the early evolutionary assembly of the sauropterygian body plan. Finally, our phylogenetic analysis supports the placement of Testudines and Archosauromorpha within Archelosauria, a result strongly corroborated by molecular data, but only recently recovered in a phylogenetic analysis using a morphology-only dataset. Our study provides evidence for the rapid diversification of sauropterygians in the aftermath of the Permo-Triassic mass extinction event and emphasises the importance of broad taxonomic sampling in reconstructing phylogenetic relationships among extinct taxa.

Around 252 million years ago, just before the start of a period of time known as the Triassic, over 90% of animals, plants and other species on Earth went extinct in what was the worst mass extinction event in the planet's history. It is thought to have happened because of an increase in volcanic eruptions that led to global warming, acid rain and other catastrophic changes in the environment. The loss of so many species caused ecosystems to restructure as the surviving species evolved to fill niches left by those that had gone extinct. On land, reptiles diversified to give rise to dinosaurs, the flying pterosaurs, and the ancestors of modern crocodiles, lizards, snakes and turtles. Some of these land-based animals evolved to live in water, resulting in many species of marine reptiles emerging during the Triassic period. This included the saurosphargids, a group of marine reptiles that lived in the Middle Triassic around 247­237 million years ago. They were 'armoured' with a shield made of broadened ribs superficially similar to that of turtles, and a covering of bony plates. However, it is unclear how the saurosphargids evolved and how closely they are related to other marine reptiles. Here, Wolniewicz et al. studied a new species of saurosphargid named Prosaurosphargis yingzishanensis that was found fossilized in a quarry in South China. The animal was around 1.5 metres long and had a chest shield and armoured plates like other saurosphargids. The characteristics of the rock surrounding the fossil suggest that this individual lived in the Early Triassic, several million years before other saurosphargid species. The team used a phylogenetic approach to infer the evolutionary relationships between P. yingzishanensis and numerous other land-based and marine reptiles based on over 220 anatomical characteristics of the animals. The resulting evolutionary tree indicated that the saurosphargids represented an early stage in the evolution of a larger group of marine reptiles known as the sauropterygians. The analysis also identified the closest land-based relatives of sauropterygians. These findings provide evidence that marine reptiles rapidly diversified in the aftermath of the mass extinction event 252 million years ago. Furthermore, they contribute to our understanding of how ecosystems recover after a major environmental crisis.

Atmosphere-inspired multilayered nanoarmor with modulable protection and delivery of Interleukin-4 for inflammatory microenvironment modulation.

Inflammatory bowel disease (IBD) has been closely associated with immune disorders and excessive M1 macrophage activation, which can be reversed by the M2-polarizing effect of interleukin-4 (IL-4). However, maintaining native IL-4 activity with its specific release in the inflammatory microenvironment and efficient biological performance remain a challenge. Inspired by the multilayered defense mechanism of the earth's atmosphere, we constructed a multilayered protective nanoarmor (NA) for IL-4 delivery (termed as IL-4@PEGRA NAs) into an intricate inflammatory microenvironment. The poly(ethylene glycol) (PEG)-ylated phenolic rosmarinic acid (RA)-grafted copolymer contains two protective layers-the intermediate polyphenol (RA molecules) and outermost shield (PEG) layers-to protect the biological activity of IL-4 and prolong its circulation in blood. Moreover, IL-4@PEGRA NAs scavenge reactive oxygen species with the specific release of IL-4 and maximize its biofunction at the site of inflammation, leading to M2 macrophage polarization and downregulation of inflammatory mediators. Simultaneously, gut microbiota dysbiosis can improve to amplify the M2-polarizing effect and inhibit the phosphatidylinositol 3 kinase/Akt signaling pathway, thereby attenuating inflammation and promoting colitis tissue repair. It provides a nature-inspired strategy for constructing an advanced multilayered NA delivery system with protective characteristics and potential for IBD management.

Identify Tcea3 as a novel anti-cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stress.

Background: Chronic pressure overload triggers pathological cardiac hypertrophy that eventually leads to heart failure. Effective biomarkers and therapeutic targets for heart failure remain to be defined. The aim of this study is to identify key genes associated with pathological cardiac hypertrophy by combining bioinformatics analyses with molecular biology experiments. Methods: Comprehensive bioinformatics tools were used to screen genes related to pressure overload-induced cardiac hypertrophy. We identified differentially expressed genes (DEGs) by overlapping three Gene Expression Omnibus (GEO) datasets (GSE5500, GSE1621, and GSE36074). Correlation analysis and BioGPS online tool were used to detect the genes of interest. A mouse model of cardiac remodeling induced by transverse aortic constriction (TAC) was established to verify the expression of the interest gene during cardiac remodeling by RT-PCR and western blot. By using RNA interference technology, the effect of transcription elongation factor A3 (Tcea3) silencing on PE-induced hypertrophy of neonatal rat ventricular myocytes (NRVMs) was detected. Next, gene set enrichment analysis (GSEA) and the online tool ARCHS4 were used to predict the possible signaling pathways, and the fatty acid oxidation relevant pathways were enriched and then verified in NRVMs. Furthermore, the changes of long-chain fatty acid respiration in NRVMs were detected using the Seahorse XFe24 Analyzer. Finally, MitoSOX staining was used to detect the effect of Tcea3 on mitochondrial oxidative stress, and the contents of NADP(H) and GSH/GSSG were detected by relevant kits. Results: A total of 95 DEGs were identified and Tcea3 was negatively correlated with Nppa, Nppb and Myh7. The expression level of Tcea3 was downregulated during cardiac remodeling both in vivo and in vitro. Knockdown of Tcea3 aggravated cardiomyocyte hypertrophy induced by PE in NRVMs. GSEA and online tool ARCHS4 predict Tcea3 involved in fatty acid oxidation (FAO). Subsequently, RT-PCR results showed that knockdown of Tcea3 up-regulated Ces1d and Pla2g5 mRNA expression levels. In PE induced cardiomyocyte hypertrophy, Tcea3 silencing results in decreased fatty acid utilization, decreased ATP synthesis and increased mitochondrial oxidative stress. Conclusion: Our study identifies Tcea3 as a novel anti-cardiac remodeling target by regulating FAO and governing mitochondrial oxidative stress.

Enhanced charge transfer and photocatalytic carbon dioxide reduction of copper sulphide@cerium dioxide p-n heterojunction hollow cubes.

Hollow structure hybrids have gained considerable attention for their ability to reduce CO2 owing to their rich active sites, high gas adsorption ability, and excellent light utilization capacity. Herein, a template-engaged strategy was provided to fabricate copper sulphide@cerium dioxide (CuS@CeO2) p-n heterojunction hollow cube photocatalysts using Cu2O cubes as a sacrificial template. The sequential steps of loading of CeO2 nanolayer, sulfidation, and etching reaction facilitate the formation of CuS@CeO2 p-n heterojunction hollow cubes. Compared with the single CuS, CeO2, and their physical mixture, the CuS@CeO2 p-n heterojunction hollow cube photocatalyst expresses a higher performance toward photocatalytic CO2 reduction under solid-gas reaction conditions due to the faster separation of photogenerated charges. The further enhanced performance of CuS@CeO2 p-n heterojunction hollow cubes was achieved by decorating pt nanoparticles due to the fact that Pt nanoparticles had a high electron affinity and CO2 adsorption capacity, and the highest CO and CH4 yields of the optimized hybrid reached 195.8 µmol g-1 h-1 and 19.96 µmol g-1 h-1, respectively. This work might provide a strategy for designing and synthesizing efficient hollow heterostructured photocatalysts for solar energy conversion and utilization.

Effects of Follicular Fluid on Physiological Characteristics and Differentiation of Fallopian Tube Epithelial Cells Implicating for Ovarian Cancer Pathogenesis.

The fallopian tube (FT) is an important reproductive organ in females. Ample evidence suggests that the distal end of FT is the original site of high-grade serous ovarian carcinoma (HGSC). FT may suffer from repeated injury and repair stimulated by follicular fluid (FF); however, this hypothesis has not been examined. In fact, the molecular mechanism of homeostasis, differentiation, and the transformation of fallopian tube epithelial cells (FTECs) resulting from the stimulation of FF are still enigmatic. In this study, we examined the effects of FF along with factors present in the FF on a variety of FTEC models, including primary cell culture, ALI (air-liquid interface) culture, and 3D organ spheroid culture. We found that FF plays a similar role to estrogen in promoting cell differentiation and organoid formation. Moreover, FF significantly promotes cell proliferation and induces cell injury and apoptosis in high concentrations. These observations may help us to investigate the mechanisms of the initiation of HGSC.

Gut Microbiota and Aging: Traditional Chinese Medicine and Modern Medicine.

The changing composition of gut microbiota, much like aging, accompanies people throughout their lives, and the inextricable relationship between both has recently attracted extensive attention as well. Modern medical research has revealed that a series of changes in gut microbiota are involved in the aging process of organisms, which may be because gut microbiota modulates aging-related changes related to innate immunity and cognitive function. At present, there is no definite and effective method to delay aging. However, Nobel laureate Tu Youyou's research on artemisinin has inspired researchers to study the importance of Traditional Chinese Medicine (TCM). TCM, as an ancient alternative medicine, has unique advantages in preventive health care and in treating diseases as it already has formed an independent understanding of the aging system. TCM practitioners believe that the mechanism of aging is mainly deficiency, and pathological states such as blood stasis, qi stagnation and phlegm coagulation can exacerbate the process of aging, which involves a series of organs, including the brain, kidney, heart, liver and spleen. Our current understanding of aging has led us to realise that TCM can indeed make some beneficial changes, such as the improvement of cognitive impairment. However, due to the multi-component and multi-target nature of TCM, the exploration of its mechanism of action has become extremely complex. While analysing the relationship between gut microbiota and aging, this review explores the similarities and differences in treatment methods and mechanisms between TCM and Modern Medicine, in order to explore a new approach that combines TCM and Modern Medicine to regulate gut microbiota, improve immunity and delay aging.

Thermal preconditioning can reduce the incidence of intraoperatively acquired pressure injuries.

Intraoperatively acquired pressure injuries (IAPIs) occur frequently among patients who undergo surgical procedures that last longer than 3 h. Several studies indicated that heat shock proteins (HSPs) play an important role in the protection of stress-induced damages in skin tissues. Hence, the aim of this study was to investigate the potential preventive effect of thermal preconditioning (TPC) on IAPIs in surgical patients and rats and to identify the differentially expressed HSP genes in response to the above treatment. TPC was performed on one group of hairless rats before the model of pressure injuries was established. Subsequently, the size of skin lesions was measured and the expression levels of mRNA and protein of HSPs of the pressured skin were detected by real-time polymerase chain reaction (RT-PCR), western blot, and immunohistochemical staining. For human studies, 118 surgical patients were randomly divided into the TPC group (n = 59) and the control group (n = 59), respectively. The temperature and pressure of sacral skin, as well as the incidence of pressure injury (PI) were detected and compared. In animal studies, TPC significantly reduced both the size and incidence of PI in rats on the second, third and fourth days post treatment. In addition, the expression levels of both mRNA and protein of HSP27 were increased in the TPC group, compared with the control group. Immunohistochemical staining showed that HSP27 was distributed in various types of dermal cells and increased in basal cells. In human studies, a significant reduction (75%) of IAPIs was observed among the patients in the TPC group. TPC can reduce the incidence of PI in rats and humans, and the upregulation of HSP27 may play an important role in this biological progress. Further studies are warranted to explore the molecular mechanism of the preventive effect in PI mediated by HSP27.

A Simple Telemetry Sensor System for Monitoring Body Temperature in Rabbits-A Brief Report.

Continuous body temperature measurement is an important means of studying inflammation and metabolic changes using experimental animals. Although expensive telemetry equipment for collecting multiple parameters is available for small animals, readily used devices for mediate- or large-sized animals are rather limited. In this study, we developed a new telemetry sensor system that can continuously monitor rabbit body temperature. The telemetry sensor was easily implanted subcutaneously in rabbits housed in the animal facility while temperature changes were continuously recorded by a personal computer. Temperature data obtained by the telemetry was consistent with the rectal temperature measured by a digital device. Analysis of body temperature changes of unstrained rabbits, either under the normal condition or fever induced by endotoxin confirms the reliability and usefulness of this system.