A novel electrochemical sensor with NiSx@MoS2 composite for efficient NO2- sensing.

Excess nitrites are potentially threatening to human health, so it is urgent to develop accurate and sensitive methods. The development of sensors can provide early warning of possible hazards and alert people to protect public health. This work presents an NiSx@MoS2-composite with excellent electrochemical activity, representing a key finding for highly sensitive NO2- detection and sensor development. With the assistance of NiSx@MoS2, this electrochemical sensor has excellent quantitative detection performance. It has a wide detection range (0.0001-0.0020 mg/mL) and a low detection limit (1.863*10-5 mg/mL) for NO2-. This electrochemical sensor maintains excellent specificity among numerous interferences, and it completes the accurate detection of different real food samples. Pleasingly, the electrochemical sensor has satisfactory repeatability stability, and potential for practical applications. It would demonstrate tremendous potential in scientific dietary guidance, food safety detection and other fields.

Diosmetin-7-O-ß-D-glucopyranoside from Pogostemonis Herba alleviated SARS-CoV-2-induced pneumonia by reshaping macrophage polarization and limiting viral replication.

ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY: To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS: The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by Western blot assay. RESULTS: Diosmetin-7-O-ß-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 0.625-2.5 µM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS: DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.

Extract from Falcaria vulgaris loaded with exosomes for the treatment of hypertension in pregnant mice: In vitro and In vivo investigations.

BACKGROUND: Hypertensive disorders during pregnancy pose significant risks to both maternal and fetal health, necessitating safe and effective therapeutic interventions. OBJECTIVE: This study aimed to investigate the potential of an extract derived from Falcaria vulgaris (FV), loaded with exosomes to form the Exo/FV complex, as a novel therapeutic agent for the management of hypertension in pregnant mice: antioxidants, antimicrobials, and phenolic compounds present in FV lower blood pressure. METHODS: The isolation of exosomes was done by ultracentrifugation methods and the FV was loaded into the exosomes by electroporation method. RESULTS: The Exo/FV was found to be spherical with diameter ranges from 20 to 30 nm and they were tested for biocompatibility in NHI 3T3 cell lines and found to be effective. This research investigated in vivo hypertension in mice induced by L-NAME and treated with FV and Exo/FV and found that AChE and MAO determine mice's redox state tends to reduce blood pressure. Increased non-protein thiol (NP-SH) and decreased lipid peroxidation were also found, and PDE-5, ACE, Arginase, and MDA activity has also been tested. CONCLUSION: This analysis showed that Exo/FV effectively treated hypertension during pregnancy.

Exploring the role and mechanisms of environmental serious games in promoting pro-environmental decision-making: a focused literature review and future research agenda.

Environmental serious games aim to heighten players' awareness and comprehension of environmental issues, thus fostering pro-environmental decision-making. Research to date has affirmed these games' effectiveness in enhancing environmental knowledge and abilities, elevating consciousness regarding environmental matters, and promoting pro-environmental behavioral intentions and actions. Nonetheless, a detailed exploration into the precise mechanisms facilitating these impacts remains scarce. Leveraging theories of motivation, cognition, affect, and behavior, this paper outlines four hypothesized mechanisms of influence and introduces an Embodied-Enactive Cognition Model as a novel perspective. It suggests that future research should expand its inquiry into the multifaceted factors that influence pro-environmental decision-making, deepen the comprehension of the intrinsic mechanisms at play, pioneer novel research methodologies, and diversify the array of categories and contextual applications of environmental serious games.

Frequency aware high-quality computer-generated holography via multilevel wavelet learning and channel attention.

Deep learning-based computer-generated holography offers significant advantages for real-time holographic displays. Most existing methods typically utilize convolutional neural networks (CNNs) as the basic framework for encoding phase-only holograms (POHs). However, recent studies have shown that CNNs suffer from spectral bias, resulting in insufficient learning of high-frequency components. Here, we propose a novel, to our knowledge, frequency aware network for generating high-quality POHs. A multilevel wavelet-based channel attention network (MW-CANet) is designed to address spectral bias. By employing multi-scale wavelet transformations, MW-CANet effectively captures both low- and high-frequency features independently, thus facilitating an enhanced representation of high-frequency information crucial for accurate phase inference. Furthermore, MW-CANet utilizes an attention mechanism to discern and allocate additional focus to critical high-frequency components. Simulations and optical experiments confirm the validity and feasibility of our method.

Eating for immunity: how diet shapes our defenses.

Emerging studies on the diet-immune axis have uncovered novel dietary immune regulators and identified crucial targets and pathways mediating the crosstalk between specific dietary components and diverse immune cell populations. Here, we discuss the recent discovery and mechanisms by which diet-derived components, such as vitamins, amino acids, fatty acids, and antioxidants, could impact immune cell metabolism, alter signaling pathways, and reprogram the overall cellular responses. We also note crucial considerations that need to be tackled to make these findings clinically relevant, acknowledging that our current understanding often relies on simplified models that may not adequately represent the intricate network of factors influencing the diet-immune axis at the whole organism level. Overall, our growing understanding of how diet shapes our defenses underscores the importance of lifestyle choices and illuminates the potential to fine-tune immune responses through targeted nutritional strategies, thereby fortifying the immune system and bolstering our defenses against diseases.

An integrative strategy used by the aphid Uroleucon formosanum to counter host sesquiterpene lactone defense: Insights from combined genomic and transcriptomic analysis.

Insect herbivores adapt and develop strategies to counteract plant chemical defenses. The aphid Uroleucon formosanum is a serious sap-sucking pest that infests lettuces containing toxic sesquiterpene lactones (STLs). Herein, we employed a combination of genome sequencing and RNA-seq transcriptome profiling to understand the mechanisms underlying phytotoxin tolerance in U. formosanum. We generated the first chromosome-level genome assembly for U. formosanum, with a total size of 453.26 Mb and a scaffold N50 of 33.22 Mb. Comparative genomic analyses revealed an enrichment of signals for positive selection and gene family expansion in immune-related pathways. Specifically, the expanded set of heat shock protein 70 (HSP70) genes showed upregulation after treatment with lactucin, suggesting that they may play a role in the immune response against STLs. The expression of takeout-like genes and cuticle-associated genes was also significantly increased in the lactucin-treated samples. Additionally, 53 cytochrome P450 monooxygenase, 30 carboxylesterase, 19 glutathione S-transferase, 32 uridine diphosphate glycosyltransferase and 63 ATP-binding cassette (ABC) transporter genes were identified in the U. formosanum genome. CYP4C1, CYP6A13 and 7 ABC genes were strongly upregulated in response to lactucin treatment, indicating the involvement of detoxifying enzymes in the tolerance of U. formosanum to STLs. Our findings suggest that the cuticle barrier, immune response and enzyme-mediated metabolic detoxification jointly enhance the tolerance of U. formosanum to phytotoxins and promote its adaptation to host plants. This study presents a valuable genomic resource and provides insights into insect adaptation to plant chemical challenges and future technological developments for pest management.

PEDOT:PSS-Based Wearable Flexible Temperature Sensor and Integrated Sensing Matrix for Human Body Monitoring.

Flexible temperature sensors have been widely used in electronic skins and health monitoring. Body temperature as one of the key physiological signals is crucial for detecting human body's abnormalities, which necessitates high sensitivity, quick responsiveness, and stable monitoring. In this paper, we reported a resistive temperature sensor designed as an ultrathin laminated structure with a serpentine pattern and a bioinspired adhesive layer, which was fabricated with a composite of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)/single-wall carbon nanotubes/reduced graphene oxide (PEDOT:PSS/SWCNTs/rGO) and polydimethylsiloxane (PDMS). The temperature sensor exhibited a high temperature sensitivity of 0.63% °C-1, coupled with outstanding linearity of 0.98 within 25-45 °C. Furthermore, it showed fast response and recovery speeds of 4.8 and 5.8 s, respectively, between 25 and 36 °C. It also demonstrated exceptional stability when subjected to stress and bending disturbances with the maximum bending interference deviation of 0.03%. Additionally, it displayed good cyclic stability over a broad temperature range from 25 to 85 °C, and the standard deviation at 25 °C is 0.14%. A series of experiments including blowing detection, respiratory monitoring with or without a mask, and during rest or sleep were conducted to show the potential of the flexible temperature sensors in human body monitoring. Furthermore, a 4 × 4 flexible temperature sensor matrix was integrated to detect and map objects such as wrenches and blood vessels through human hand skin. The results were consistent with those of infrared measurements. The flexible temperature sensor is capable of real-time temperature monitoring and has the potential in tracking human respiration, assessing sleep quality, and mapping the temperature of various objects.

Burden of Herpes Zoster in Individuals With Chronic Conditions in the Republic of Korea: A Nationwide Population-Based Database Study.

Background: Chronic conditions (CCs) may increase the risk of herpes zoster (HZ) infection, leading to a greater healthcare burden in these individuals compared to those without CCs. It is therefore clinically important to quantify HZ disease burden in individuals with and without CCs, given the rapidly aging population in the Republic of Korea (ROK). Methods: This retrospective cohort study examines the trends in incidence rates (IRs) and incidence rate ratios (IRRs) in individuals aged ≥18 years with CCs, using the National Health Insurance Service National Sample Cohort (NHIS-NSC) database from 2010 to 2019. These patients were stratified by age group, sex, HZ complications, and CCs. The annual average number of HZ patients, IRs, and IRRs were calculated for individuals with and without CCs. Results: In total, 729 347 patients with HZ were eligible for the study. HZ IRs were highest in patients with diabetes, followed by chronic obstructive pulmonary disease, chronic kidney disease, asthma, and chronic liver disease, with HZ IRRs following a similar trend. Overall, HZ IRs generally increased with age, typically peaking at 60-64 or 65-69 years, and were similar for females and males. HZ IRs were highest among patients without complications, followed by HZ with other, cutaneous, ocular, and neurologic complications across all CCs. For each of the CCs, HZ IRs were consistently higher than those of the non-CC population regardless of sex. Conclusions: The findings of this study reiterate the importance of HZ prevention for healthy aging, especially for CC populations at increased risk of HZ in the ROK.

Identification of a Novel Frameshift variant of the ATRX gene: a Case Report and Review of the genotype-phenotype relationship.

BACKGROUND: X-linked intellectual disability-hypotonic facies syndrome-1 (MRXHF1) and Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome are caused by pathogenic variant in the ATRX gene, a member of the switch/sucrose non-fermentable (SWI-SNF) protein family that exhibits chromatin remodeling activity. These syndromes show a wide spectrum of clinical manifestations, such as distinctive dysmorphic features, mild-to-profound intellectual disability, motor development delay, seizures, urogenital abnormalities, and gastrointestinal disorders. CASE PRESENTATION AND LITERATURE REVIEW: A 3-year-old boy from a Chinese non-consanguineous family was diagnosed with MRXHF1 by whole-exome sequencing. Comprehensive family history information was obtained. The Medline database was searched until 1st Aug 2023 for articles related to ATRX pathogenic variant. Data on gene/protein mutations and clinical symptoms were extracted. The proband showed intellectual disability, motor development delay, typical facial abnormalities, urogenital defect, behavior problems, and optical nerve dysplasia. A novel frameshift mutation c.399_400dup, (p.Leu134Cysfs*2) in the ATRX gene was the primary cause, which occurs right before the ATRXDNMT3-DNMT3L (ADD) domain of ATRX protein. Missense mutation is the most common variation type. The ADD and helicase-like domains are the most frequently affected domains. Epilepsy, congenital heart disease, urogenital defect, acoustic defect, and optical defect are more prevalent in patients with frameshift mutations compared to those with missense mutations. There are more urogenital defects with C-terminal frameshift mutations than with N-terminal frameshift mutations. CONCLUSION: We described a novel frameshift mutation in the ATRX gene in a patient with MRXHF1 syndrome and summarized the genotype-phenotype relationship of ATRX pathogenic variant by variation type and affected protein domain. The regulatory mechanism underlying ATRX variant requires comprehensive analysis in future studies.

Senolytic effect of triterpenoid complex from Ganoderma lucidum on adriamycin-induced senescent human hepatocellular carcinoma cells model in vitro and in vivo.

Background: Ganoderma lucidum (G. lucidum) is a famous medicinal mushroom that has been reported to prevent and treat a variety of diseases. Different extractions from G. lucidum have been used to manage age-related diseases, including cancer. Nevertheless, the senolytic activity of G. lucidum against senescent cancer cells has not been investigated. Although cellular senescence causes tumor growth inhibition, senescent cells promote the growth of the neighboring tumor cells through paracrine effects. Therefore, the elimination of senescent cells is a new strategy for cancer treatment. Methods: In this study, senescence was triggered in HCC cells by the chemotherapeutic agent Adriamycin (ADR), and subsequently, cells were treated with TC to assess its senolytic activity. Results: We found for the first time that the triterpenoid complex (TC) from G. lucidum had senolytic effect, which could selectively eliminate adriamycin (ADR)-induced senescent cells (SCs) of hepatocellular carcinoma (HCC) cells via caspase-dependent and mitochondrial pathways-mediated apoptosis and reduce the levels of senescence markers, thereby inhibiting the progression of cancers caused by SCs. TC could block autophagy at the late stage in SCs, resulting in a significant activation of TC-induced apoptosis. Furthermore, TC inhibited the senescence-associated secretory phenotype (SASP) in SCs through the inhibition of NF-κB, TFEB, P38, ERK, and mTOR signaling pathways and reducing the number of SCs. Sequential administration of ADR and TC in vivo significantly reduced tumor growth and reversed the toxicity of ADR. Conclusion: A triterpenoid complex isolated from G. lucidum may serve as a novel senolytic agent against SCs, and its combination with chemotherapeutic agents may enhance their antitumor efficacy.

Proteome-scale tissue mapping using mass spectrometry based on label-free and multiplexed workflows.

Multiplexed bimolecular profiling of tissue microenvironment, or spatial omics, can provide deep insight into cellular compositions and interactions in healthy and diseased tissues. Proteome-scale tissue mapping, which aims to unbiasedly visualize all the proteins in a whole tissue section or region of interest, has attracted significant interest because it holds great potential to directly reveal diagnostic biomarkers and therapeutic targets. While many approaches are available, however, proteome mapping still exhibits significant technical challenges in both protein coverage and analytical throughput. Since many of these existing challenges are associated with mass spectrometry-based protein identification and quantification, we performed a detailed benchmarking study of three protein quantification methods for spatial proteome mapping, including label-free, TMT-MS2, and TMT-MS3. Our study indicates label-free method provided the deepest coverages of ∼3500 proteins at a spatial resolution of 50 µm and the highest quantification dynamic range, while TMT-MS2 method holds great benefit in mapping throughput at >125 pixels per day. The evaluation also indicates both label-free and TMT-MS2 provide robust protein quantifications in identifying differentially abundant proteins and spatially co-variable clusters. In the study of pancreatic islet microenvironment, we demonstrated deep proteome mapping not only enables the identification of protein markers specific to different cell types, but more importantly, it also reveals unknown or hidden protein patterns by spatial co-expression analysis.

Bisphosphonium cation based metal halide glass scintillators with tunable melting points.

Organic-inorganic metal halide (OIMH) glass offers the advantages of large-scale production, high transparency, and minimal light scattering. However, undesired crystallization in OIMH glass can occur, leading to deteriorated transparency. Herein, a series of bisphosphonium organic cations were designed to construct Mn-based metal halide crystals with a photoluminescence quantum yield (PLQY) near unity, alongside the development of highly thermally stable OIMH glasses. Two strategies were employed to lower the melting point of OIMH: alkyl chain elongation and fluorine substitution. The (Hex-3,4-2F)MnBr4·MeOH (Hex-3,4-2F = hexane-1,6-diylbis((3,4-difluorobenzyl)diphenylphosphonium)) crystal delivers a glass transition temperature of 100 °C and the highest T g/T m ratio (0.82) among OIMHs. The resulting OIMH glass exhibits a PLQY of 47.6%, achieves an impressive resolution of 25 lp mm-1 in X-ray imaging, and remains transparent even after being heated at 90 °C for six weeks. These bisphosphonium-based OIMH glasses present a feasible design for the practical application of OIMH glasses in radiation detection.

A highly reactive soybean oil-based superhydrophobic polyurethane film with long-lasting antifouling and abrasion resistance.

Superhydrophobic polyurethanes offer robust hydrophobicity and corrosion resistance. However, it is essential to consider the durability and environmental constraints associated with these materials. This study prepared a bio-based superhydrophobic polyurethane coating film using epoxidized soybean oil, superhydrophobically modified silica nanoparticles, and OH-PDMS-OH as surface modifiers. The coating film exhibited sustained super-hydrophobicity and an excellent antifouling effect for pu-erh tea and edible oils, among other substances, after 14 days of immersion in solutions with different pH values, 28 days of exposure to air, and 2000 abrasion cycles. This finding can be applied to the development of daily indoor and outdoor antifouling protective coatings and provides a new method for the preparation of green and durable superhydrophobic antifouling coating films.

Evaluation of Efficiency of Liposome-Entrapped Iridium(III) Complexes Inhibiting Tumor Growth In Vitro and In Vivo.

In this paper, three new iridium(III) complexes: [Ir(piq)2(DFIPP)]PF6 (piq = deprotonated 1-phenylisoquinoline, DFIPP = 3,4-difluoro-2-(1H-imidazo[4,5-f][1,10]phenenthrolin-2-yl)phenol, 3a), [Ir(bzq)2(DFIPP)]PF6 (bzq = deprotonated benzo[h]quinoline, 3b), and [Ir(ppy)2(DFIPP)]PF6 (ppy = deprotonated 1-phenylpyridine, 3c), were synthesized and characterized. The complexes were found to be nontoxic to tumor cells via 3-(4,5-dimethylthiazole-2-yl)-diphenyltetrazolium bromide (MTT) assay. Surprisingly, its liposome-entrapped complexes 3alip, 3blip, and 3clip on B16 cells showed strong cytotoxicity (IC50 = 13.6 ± 2.8, 9.6 ± 1.1, and 18.9 ± 2.1 µM). Entry of 3alip, 3blip, and 3clip into B16 cells decreases mitochondrial membrane potential, regulates Bcl-2 family proteins, releases cytochrome c, triggers caspase family cascade reaction, and induces apoptosis. In addition, we also found that 3alip, 3blip, and 3clip triggered ferroptosis and autophagy. In vivo studies demonstrated that 3blip inhibited melanoma growth in C57 mice with a high inhibitory rate of 83.95%, and no organic damage was found in C57 mice.

Genome-wide analysis of UDP-glycosyltransferase family in Citrus sinensis and characterization of a UGT gene encoding flavonoid 1-2 rhamnosyltransferase.

UDP-glycosyltransferases (UGTs) play a crucial role in the glycosylation of secondary metabolites in plants, which is of significant importance for growth and response to biotic or abiotic stress. Despite the wide identification of UGT family members in various species, limited information is available regarding this family in citrus. In this study, we identified 87 UGT genes from the Citrus sinensis genome and classified them into 14 groups. We characterized their gene structures and motif compositions, providing insights into the molecular basis underlying discrepant functions of UGT genes within each evolutionary branch. Tandem duplication events were found to be the main driving force behind UGT gene expansion. Additionally, we identified numerous cis-acting elements in the promoter region of UGT genes, including those responsive to light, growth factors, phytohormones, and stress conditions. Notably, light-responsive elements were found with a frequency of 100 %. We elucidated the expression pattern of UGTs during fruit development in Citrus aurantium using RNA-seq and quantitative real-time PCR (qRT-PCR), revealing that 10 key UGT genes are closely associated with biosynthesis of bitter flavanone neohesperidosides (FNHs). Furthermore, we identified Ca1,2RhaT as a flavonoid 1-2 rhamnosyltransferase (1,2RhaT) involved in FNHs biosynthesis for the first time. Isolation and functional characterization of the gene Ca1,2RhaT from Citrus aurantium in vitro and in vivo indicated that Ca1,2RhaT encoded a citrus 1,2RhaT and possessed rhamnosyl transfer activities. This work provides comprehensive information on the UGT family while offering new insights into understanding molecular mechanisms regulating specific accumulation patterns of FNHs or non-bitter flavanone rutinosides (FRTs) in citrus.

Analysis of Clinical Diagnosis and Treatment Modes for Congenital Branchial Cleft Anomalies.

OBJECTIVE: The objective of this study was to investigate and assess the clinical data of 123 patients diagnosed with congenital branchial cleft anomalies (CBCAs), to summarize pivotal aspects concerning their clinical diagnosis and treatment process. MATERIALS AND METHODS: The authors conducted a retrospective analysis of 123 patients who underwent surgical intervention for CBCAs at our institution between August 2005 and September 2021. The clinical demographic characteristics of the patients, primary symptoms, treatment chronology, preoperative diagnostic assessments, surgical strategies, occurrences of postoperative complications, and rates of recurrence were subjected to statistical analysis. RESULTS: Among the enrolled patients, there were 43 cases (34.9%) of congenital first branchial cleft anomalies (CFBCA), 76 cases (61.8%) of congenital second branchial cleft anomalies (CSBCA), and 4 cases (3.3%) of congenital third branchial cleft anomalies (CTBCA), with no cases of congenital fourth branchial anomalies (CFBA). Notably, among all cases, 43 anomalies were situated in the upper one-third of the sternocleidomastoid muscle, while 80 anomalies were located in the lower one-third. Different surgical approaches were selected for patients based on the specific type of anomaly presented. Following surgery, there was recurrence in 14 cases, with factors such as patient age, clinical categorization, lesion type, and history of preoperative infection and surgical intervention identified as primary risk factors for it. CONCLUSION: CBCAs represent comparatively uncommon disorders affecting the head and cervical regions in clinical practice. Diagnostic modes such as ultrasonography and lipiodol contrast radiography can be used for accurate diagnosis, with surgical intervention serving as the primary therapeutic method.

Petroleum hydrocarbons and colored dissolved organic matter shape marine oil-degrading microbiota in different patterns.

Both petroleum hydrocarbons (PHCs) from oil pollution and colored dissolved organic matter (CDOM) have great influences on the marine microbial community as carbon source factors. However, their combined effects and the specific influence patterns have been kept unclear. This study selected the northeastern South China Sea (NSCS), a typical oil contaminated area, and investigated the characteristics of oil-degrading microbiota in the seawaters by high-throughput sequencing and the relationships with PHCs and CDOM as well as other environmental factors. The results showed the oil pollution had induced the enrichment of oil-degrading bacteria and oil-degrading functional genes, resulting in the core function of oil-degrading microbiota for shaping the microbial community. The Mantel test indicated carbon source factors played the dominant role in shaping the oil-degrading microbiota, compared with geographical distance and other non­carbon source factors. The influence patterns and strength of PHCs and CDOM on oil-degrading microbiota were further comprehensively analyzed. PHCs played a driving role in the differentiation of oil-degrading microbiota, while CDOM played a stabilizing role for the community similarity. The constructed structural equation model confirmed their distinct influence patterns and also explored the mediating effects of bulk organic carbon. This work not only revealed the important impact of oil pollution on marine microbial communities, but also made people realize the self-regulation ability of the marine environment through the endogenous organic matter.

New drug combination regimen based on pharmacokinetic characteristics-Erdafitinib combined with sertraline or duloxetine.

The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors.

Two new mouse alleles of Ocm and Slc26a5.

The genes Ocm (encoding oncomodulin) and Slc26a5 (encoding prestin) are expressed strongly in outer hair cells and both are involved in deafness in mice. However, it is not clear if they influence the expression of each other. In this study, we characterise the auditory phenotype resulting from two new mouse alleles, Ocmtm1e and Slc26a5tm1Cre. Each mutation leads to absence of detectable mRNA transcribed from the mutant allele, but there was no evidence that oncomodulin regulates expression of prestin or vice versa. The two mutants show distinctive patterns of auditory dysfunction. Ocmtm1e homozygotes have normal auditory brainstem response thresholds at 4 weeks old followed by progressive hearing loss starting at high frequencies, while heterozygotes show largely normal thresholds until 6 months of age, when signs of worse thresholds are detected. In contrast, Slc26a5tm1Cre homozygotes have stable but raised thresholds across all frequencies tested, 3 to 42 kHz, at least from 4 to 8 weeks old, while heterozygotes have raised thresholds at high frequencies. Distortion product otoacoustic emissions and cochlear microphonics show deficits similar to auditory brainstem responses in both mutants, suggesting that the origin of hearing impairment is in the outer hair cells. Endocochlear potentials are normal in the two mutants. Scanning electron microscopy revealed normal development of hair cells in Ocmtm1e homozygotes but scattered outer hair cell loss even at 4 weeks old when thresholds appeared normal, indicating that there is not a direct relationship between numbers of outer hair cells present and auditory thresholds.