Dual-modal biosensor for mercuric ion detection based on Cu2O@Cu2S/D-TA COF heterojunction with excellent catalase-like, electrochemical and photoelectrochemical properties.

In this study, a dual-mode biosensor based on the heterojunction of Cu2O@Cu2S/D-TA COF was constructed for ultra-sensitive detection of Hg2+ using both photoelectrochemical and electrochemical approaches. Briefly, a 2D ultra-thin covalent organic framework film (D-TA COF film) with excellent photoelectrochemical signals was prepared on ITO surfaces through an in situ growth method. Subsequently, the probe H1 was immobilized onto the biosensor via Au-S bonds. In the presence of Hg2+, the formation of T-Hg2+-T complexes triggered hybridization chain reactions (HCR), leading to the attachment of abundant Cu2O@Cu2S probes onto the biosensor. As a p-type semiconductor, Cu2O@Cu2S could form a heterojunction with the underlying D-TA COF films. Meanwhile, it exhibited catalase-like activity, and the O2 produced by its catalytic decomposition of H2O2 can interact with the D-TA COF films, thus achieving double amplification of the photocurrent signal. Benefiting from the excellent and inherent Cu2+/Cu+ redox pairs of Cu2O@Cu2S, satisfactory differential pulse voltammetry (DPV) signals were obtained. As expected, the dual-mode biosensor was realized with wider linear ranges and low detection limits. Additionally, the analytical performance for Hg2+ in real water samples was excellent. Briefly, this suggested approach offers a facile and highly efficient modality for monitoring heavy metal ions in aquatic environments.

Continuous positive airway pressure combined with small-tidal-volume ventilation on arterial oxygenation and pulmonary shunt during one-lung ventilation in patients undergoing video-assisted thoracoscopic lobectomy: A randomized, controlled study.

BACKGROUND: One-lung ventilation (OLV) is frequently applied during video-assisted thoracoscopic surgery (VATS) airway management to collapse and isolate the nondependent lung (NL). OLV can give rise to hypoxemia as a result of the pulmonary shunting produced. Our study aimed to assess the influence of continuous positive airway pressure (CPAP) combined with small-tidal-volume ventilation on improving arterial oxygenation and decreasing pulmonary shunt rate (QS/QT) without compromising surgical field exposure during OLV. METHODS: Forty-eight patients undergoing scheduled VATS lobectomy were enrolled in this research and allocated into three groups at random: C group (conventional ventilation, no NL ventilation intervention was performed), LP group (NL was ventilated with lower CPAP [2 cmH2O] and a 40-60 mL tidal volume [TV]), and HP group (NL was ventilated with higher CPAP [5 cmH2O] and a 60-80 mL TV). Record the blood gas analysis data and calculate the QS/QT at the following time: at the beginning of the OLV (T0), 30 min after OLV (T1), and 60 min after OLV (T2). Surgeons blinded to ventilation techniques were invited to evaluate the surgical fields. RESULTS: The demography data of the three groups were consistent with the surgical data. At T1, PaO2 in the HP group was substantially higher compared to the C group (P < 0.05), while there was no significant difference in the LP group (P > 0.05). At T1-T2, PaCO2 in the LP and HP groups was significantly less than that in the C group (P < 0.05). At T1, the QS/QT values of groups C, LP, and HP were 29.54 ± 6.89%, 22.66 ± 2.08%, and 19.64 ± 5.76%, respectively, and the QS/QT values in the LP and HP groups markedly reduced (P < 0.01). The surgical field's evaluation by the surgeon among the three groups was not notable (P > 0.05). CONCLUSION: CPAP combined with small-tidal-volume ventilation effectively improved arterial oxygenation and reduced QS/QT and PaCO2 without compromising surgical field exposure during OLV. Among them, 5 cmH2O CPAP + 60-80 ml TV ventilation had a better effect on improving oxygenation.

Navigating the B vitamins: Dietary diversity, microbial synthesis, and human health.

B vitamins are intricately involved in various physiological processes vital for health. Their significance is complicated by the heterogeneous landscape of B vitamin distribution in diets and the contributions of the gut microbiota. Here, we delve into the impact of these factors on B vitamins and introduce strategies, with a focus on microbiota-based therapeutic options, to enhance their availability for improved well-being. Additionally, we provide an ecological and evolutionary perspective on the importance of B vitamins to human-microbiota interactions. In the dynamic realms of nutrition and microbiome science, these essential micronutrients continue to play a fundamental role in our understanding of disease development.

Grassland health assessment based on indicators monitored by UAVs: a case study at a household scale.

Grassland health assessment (GHA) is a bridge of study and management of grassland ecosystem. However, there is no standardized quantitative indicators and long-term monitor methods for GHA at a large scale, which may hinder theoretical study and practical application of GHA. In this study, along with previous concept and practices (i.e., CVOR, the integrated indexes of condition, vigor, organization and resilience), we proposed an assessment system based on the indicators monitored by unmanned aerial vehicles (UAVs)-UAVCVOR, and tested the feasibility of UAVCVOR at typical household pastures on the Qinghai-Tibetan Plateau, China. Our findings show that: (1) the key indicators of GHA could be measured directly or represented by the relative counterpart indicators that monitored by UAVs, (2) there was a significantly linear relationship between CVOR estimated by field- and UAV-based data, and (3) the CVOR decreased along with the increasing grazing intensity nonlinearly, and there are similar tendencies of CVOR that estimated by the two methods. These findings suggest that UAVs is suitable for GHA efficiently and correctly, which will be useful for the protection and sustainable management of grasslands.

UAV Assisted Livestock Distribution Monitoring and Quantification: A Low-Cost and High-Precision Solution.

Grazing management is one of the most widely practiced land uses globally. Quantifying the spatiotemporal distribution of livestock is critical for effective management of livestock-grassland grazing ecosystem. However, to date, there are few convincing solutions for livestock dynamic monitor and key parameters quantification under actual grazing situations. In this study, we proposed a pragmatic method for quantifying the grazing density (GD) and herding proximities (HP) based on unmanned aerial vehicles (UAVs). We further tested its feasibility at three typical household pastures on the Qinghai-Tibetan Plateau, China. We found that: (1) yak herds grazing followed a rotational grazing pattern spontaneously within the pastures, (2) Dispersion Index of yak herds varied as an M-shaped curve within one day, and it was the lowest in July and August, and (3) the average distance between the yak herd and the campsites in the cold season was significantly shorter than that in the warm season. In this study, we developed a method to characterize the dynamic GD and HP of yak herds precisely and effectively. This method is ideal for studying animal behavior and determining the correlation between the distribution of pastoral livestock and resource usability, delivering critical information for the development of grassland ecosystem and the implementation of sustainable grassland management.

Anlotinib combined with TAS-102 as the third-line treatment for a patient with metastatic colon cancer: A case report.

Chemotherapy combined with targeted therapy is a first-line and second-line treatment for metastatic colorectal cancer(mCRC), which has brought survival benefits to mCRC patients, however, disease progression is inevitable. More than 60% of patients still needed third-line treatment after the progress of second-line treatment. After the failure of second-line chemotherapy, treatment compliance and the physical tolerance of patients both decrease. Therefore, choosing an appropriate third-line treatment regimen is key to prolonging survival and improving quality of life. As a novel cytotoxic antitumor drug, trifluridine/tipiracil (TAS-102) is composed of trifluridine (FTD) and tipiracil hydrochloride (TPI). FTD can directly bind to the DNA of cancer cells to cause DNA dysfunction, thereby exerting antitumor effects. TPI can inhibit the degradation of FTD, thereby increasing its cytotoxicity. The few side effects of TAS-102 has become an important reason why clinicians present it as a treatment option to the patient for consideration, clinical trial data for progression free survival are lacking. The exploration of third-line treatment regimens with drug combinations has attracted much attention. This article reports a case of metastatic colon cancer (RAS/BRAF wild type, pMMR/Non-MSI-H), after failure of first-line and second-line therapies, the patient was eventually treated with anlotinib combined with TAS-102 as the third-line treatment. The treatment has shown good efficacy, with a long PFS benefit for more than 20 months and mild adverse reactions. This case reports demonstrates that anlotinib combined with TAS-102 is a promising third-line treatment regimen for refractory mCRC, and provides proof-of-concept for the clinical exploration of optimal third-line combination treatment regimens.

The m6A demethylase ALKBH5-mediated upregulation of DDIT4-AS1 maintains pancreatic cancer stemness and suppresses chemosensitivity by activating the mTOR pathway.

BACKGROUND: Chemoresistance is a major factor contributing to the poor prognosis of patients with pancreatic cancer, and cancer stemness is one of the most crucial factors associated with chemoresistance and a very promising direction for cancer treatment. However, the exact molecular mechanisms of cancer stemness have not been completely elucidated. METHODS: m6A-RNA immunoprecipitation and sequencing were used to screen m6A-related mRNAs and lncRNAs. qRT-PCR and FISH were utilized to analyse DDIT4-AS1 expression. Spheroid formation, colony formation, Western blot and flow cytometry assays were performed to analyse the cancer stemness and chemosensitivity of PDAC cells. Xenograft experiments were conducted to analyse the tumour formation ratio and growth in vivo. RNA sequencing, Western blot and bioinformatics analyses were used to identify the downstream pathway of DDIT4-AS1. IP, RIP and RNA pulldown assays were performed to test the interaction between DDIT4-AS1, DDIT4 and UPF1. Patient-derived xenograft (PDX) mouse models were generated to evaluate chemosensitivities to GEM. RESULTS: DDIT4-AS1 was identified as one of the downstream targets of ALKBH5, and recruitment of HuR onto m6A-modified sites is essential for DDIT4-AS1 stabilization. DDIT4-AS1 was upregulated in PDAC and positively correlated with a poor prognosis. DDIT4-AS1 silencing inhibited stemness and enhanced chemosensitivity to GEM (Gemcitabine). Mechanistically, DDIT4-AS1 promoted the phosphorylation of UPF1 by preventing the binding of SMG5 and PP2A to UPF1, which decreased the stability of the DDIT4 mRNA and activated the mTOR pathway. Furthermore, suppression of DDIT4-AS1 in a PDX-derived model enhanced the antitumour effects of GEM on PDAC. CONCLUSIONS: The ALKBH5-mediated m6A modification led to DDIT4-AS1 overexpression in PDAC, and DDIT-AS1 increased cancer stemness and suppressed chemosensitivity to GEM by destabilizing DDIT4 and activating the mTOR pathway. Approaches targeting DDIT4-AS1 and its pathway may be an effective strategy for the treatment of chemoresistance in PDAC.

Schisantherin D from Schisandra chinensis (Turcz.) Baill. exhibits anti-liver fibrosis capacity via modulating ETBR involved signaling, an in vitro and in vivo study.

Excess levels of chemical hepatotoxicants (alcohol, aflatoxin B1), oxidative drugs (acetaminophen) and some cytokines (ET-1, TGF-ß1) can induce chronic or acute liver injury. After these, the severe hepatic disease, especially the liver fibrosis (LF) occurs without taking measures, which brings threat to human health. The dibenzocyclooctadiene lignans of S. chinensis (SCDLs) were found to act as the hepatoprotective components via blocking endothelin B receptor (ETBR). While study on its anti-LF mechanisms especially for its refined compound of schisantherin D (SC-D) is still a lack. So this study aims to investigate the anti-fibrosis effect of SC-D with in vitro and in vivo assays. Bioinformatics analysis revealed the close relations of ETBR to Smad2, Smad3, Nrf2, etc. in LF-related signaling pathways (such as TGF-ß/Smad and Nrf2/ARE). Histopathological staining on livers showed the recovery trend in SC-D treated LF mice. SC-D also modulated expressions of ETBR and fibrosis or anti-oxidative related proteins (such as TIMP1, p-Smad2/3, Nrf2, Smad7, etc.) in LF mice livers. Serum levels of TNF-α, COLI, ALT, AST and LDH in SC-D treated mice were also downregulated compared with LF mice, and upregulated expression of GSH. In vitro studies, SC-D also modulated expressions of LF-related proteins to the normal tendency in LX-2 cell, while weakened its anti- LX-2 proliferation effect by transfections of si-Smad7 or si-Nrf2. Accordingly the anti-LF approach of SC-D showed relations with modulating ETBR linked fibrosis and anti-oxidative related signaling. Also, Smad7 and Nrf2 might be the key factors for SC-D mediated anti-LF effect.

Advances in the human skin microbiota and its roles in cutaneous diseases.

Skin is the largest organ in the human body, and the interplay between the environment factors and human skin leads to some skin diseases, such as acne, psoriasis, and atopic dermatitis. As the first line of human immune defense, skin plays significant roles in human health via preventing the invasion of pathogens that is heavily influenced by the skin microbiota. Despite being a challenging niche for microbes, human skin is colonized by diverse commensal microorganisms that shape the skin environment. The skin microbiota can affect human health, and its imbalance and dysbiosis contribute to the skin diseases. This review focuses on the advances in our understanding of skin microbiota and its interaction with human skin. Moreover, the potential roles of microbiota in skin health and diseases are described, and some key species are highlighted. The prevention, diagnosis and treatment strategies for microbe-related skin diseases, such as healthy diets, lifestyles, probiotics and prebiotics, are discussed. Strategies for modulation of skin microbiota using synthetic biology are discussed as an interesting venue for optimization of the skin-microbiota interactions. In summary, this review provides insights into human skin microbiota recovery, the interactions between human skin microbiota and diseases, and the strategies for engineering/rebuilding human skin microbiota.

Research Progress in Immunotherapy of NSCLC With EGFR-Sensitive Mutations.

Lung cancer is a malignant tumor with high incidence and mortality across the world. The use of immune checkpoint inhibitors for lung cancer has improved the prognosis of some lung cancer patients to a greater extent and provided a new direction for the clinical treatment of lung cancer. Immunotherapy still has limitations in terms of its appropriate population and adverse reactions. Particularly for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation, there has been no major breakthrough in current immunotherapy. Whether immunotherapy can bring new benefits after drug resistance is induced by tyrosine kinase inhibitor-targeted therapy and whether the combination of immunotherapy with other treatments can improve the prognosis remain to be studied in depth. In this article, we provide a detailed review of the relevant characteristics of the tumor microenvironment of NSCLC with EGFR mutation and the current research on immunotherapy for NSCLC with EGFR mutation.

Bi-layered nanofibrous membrane with osteogenic and antibacterial functions for periodontal tissue regeneration.

Guided tissue regeneration (GTR) membranes have great potential to promote periodontal tissue regeneration and reestablishment. However, the regeneration potential and microbial infection resistance of current GTR membranes still need to be improved. Here, a bi-layered nanofibrous membrane on the basis of poly (lactic-co-glycolic acid) (PLGA)/gelatin with osteogenic and antibacterial functions was fabricated for periodontal tissue regeneration. The antimicrobial layer (AL) of the bi-layered nanofibrous membrane was composed of nanofibrous PLGA/gelatin nanofibers loaded with nano-silver (nAg), while the osteoconductive layer (OL) of the nanofibrous membrane consisted of PLGA/gelatin nanofibers loaded with nano-hydroxyapatite (nHA). The bi-layered nanofibrous membrane was examined by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectrometry (XPS) and X-ray diffractometry (XRD). The results showed that nHA and nAg particles were well evenly loaded or embedded in PLGA/gelatin nanofibers. The cell culture experiments suggested that the bi-layered nanofibrous membrane possessed good cytocompatibility and the OL of the bi-layered nanofibrous membrane possessed an enhanced osteogenic capacity for human osteoblast-like cells (MG63), which was verified by the good cell viability and the increased alkaline phosphatase (ALP) activity, respectively. The results of in vitro antimicrobial study displayed that the AL of the bi-layered nanofibrous membrane possessed an effective antibacterial capability. In conclusion, the prepared bi-layered nanofibrous membrane with osteogenic and antibacterial functions may have great potential for periodontal tissue regeneration and reestablishment.[Formula: see text].

Advances in the Relationships Between Cow's Milk Protein Allergy and Gut Microbiota in Infants.

Cow's milk protein allergy (CMPA) is an immune response to cow's milk proteins, which is one of the most common food allergies in infants and young children. It is estimated that 2-3% of infants and young children have CMPA. The diet, gut microbiota, and their interactions are believed to be involved in the alterations of mucosal immune tolerance, which might lead to the development of CMPA and other food allergies. In this review, the potential molecular mechanisms of CMPA, including omics technologies used for analyzing microbiota, impacts of early microbial exposures on CMPA development, and microbiota-host interactions, are summarized. The probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and other modulation strategies for gut microbiota and the potential application of microbiota-based design of diets for the CMPA treatment are also discussed. This review not only summarizes the current studies about the interactions of CMPA with gut microbiota but also gives insights into the possible CMPA treatment strategies by modulating gut microbiota, which might help in improving the life quality of CMPA patients in the future.

Exploring Gut Microbiota in Patients with Colorectal Disease Based on 16S rRNA Gene Amplicon and Shallow Metagenomic Sequencing.

The gastrointestinal tract, the largest human microbial reservoir, is highly dynamic. The gut microbes play essential roles in causing colorectal diseases. In the present study, we explored potential keystone taxa during the development of colorectal diseases in central China. Fecal samples of some patients were collected and were allocated to the adenoma (Group A), colorectal cancer (Group C), and hemorrhoid (Group H) groups. The 16S rRNA amplicon and shallow metagenomic sequencing (SMS) strategies were used to recover the gut microbiota. Microbial diversities obtained from 16S rRNA amplicon and SMS data were similar. Group C had the highest diversity, although no significant difference in diversity was observed among the groups. The most dominant phyla in the gut microbiota of patients with colorectal diseases were Bacteroidetes, Firmicutes, and Proteobacteria, accounting for >95% of microbes in the samples. The most abundant genera in the samples were Bacteroides, Prevotella, and Escherichia/Shigella, and further species-level and network analyses identified certain potential keystone taxa in each group. Some of the dominant species, such as Prevotella copri, Bacteroides dorei, and Bacteroides vulgatus, could be responsible for causing colorectal diseases. The SMS data recovered diverse antibiotic resistance genes of tetracycline, macrolide, and beta-lactam, which could be a result of antibiotic overuse. This study explored the gut microbiota of patients with three different types of colorectal diseases, and the microbial diversity results obtained from 16S rRNA amplicon sequencing and SMS data were found to be similar. However, the findings of this study are based on a limited sample size, which warrants further large-scale studies. The recovery of gut microbiota profiles in patients with colorectal diseases could be beneficial for future diagnosis and treatment with modulation of the gut microbiota. Moreover, SMS data can provide accurate species- and gene-level information, and it is economical. It can therefore be widely applied in future clinical metagenomic studies.