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Abstract Background The mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer’s Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity. Methods This is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography–functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization. Results A total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus. Conclusion Effects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS. Trial registration ClinicalTrials.gov, NCT 03920826; Registration Date: 2019-04-19.

IntroductionFerroptosis is a crucial process contributing to neuronal damage following intracerebral hemorrhage (ICH). Didang Tang (DDT), a traditional therapeutic, has been used clinically to manage ICH for many years, yet the molecular mechanisms by which by DDT protects neurons from ferroptosis after ICH remain elusive.MethodsThis study utilized high-performance liquid chromatography-based fingerprint analysis to characterize DDT’s chemical composition. An ICH rat model and hemin and erastin-induced PC12 cell ferroptosis models were developed to investigate DDT’s neuroprotective mechanisms. Histological assessments of brain tissue morphology and iron deposition were performed using hematoxylin-eosin, Nissl, and Perl’s blue staining. Neurological function was evaluated using Longa and Berderson scores, while lipid peroxidation was measured using biochemical assays and flow cytometry. Protein expression levels of ferroptosis- and endoplasmic reticulum stress (ERS)-related markers were analyzed via Western blotting and immunofluorescence.ResultsOur results demonstrated that DDT reduced hematoma volume, decreased iron deposition, lowered malondialdehyde (MDA) levels, and upregulated glutathione peroxidase (GPX4) and SLC7A11 expression in affected brain regions. Furthermore, DDT downregulated GRP78 expression and inhibited the PERK/eIF2α/ATF4/CHOP/GPX4 pathway, exerting strong neuroprotective effects. The fluorescence staining results of MAP2/GPX4 and MAP2/CHOP suggested that DDT may regulate neuronal ferroptosis and ERs to exert the protective effect. In vitro experiments using hemin- and erastin-induced neuron-derived PC12 cells as neuronal ferroptosis models developed in our laboratory corroborated these in vivo findings, showing increased survival and reduced lipid peroxidation in DDT-treated cells, along with similar inhibitory effects on ferroptosis and ERS. Molecular docking suggested that DDT components, such as sennoside B, amygdalin, rhein, and emodin, interact favorably with PERK/eIF2α/ATF4/CHOP signaling pathway proteins, highlighting their potential role in DDT’s anti-ferroptosis effects.ConclusionDDT alleviates neuronal ferroptosis after ICH by modulating the PERK/eIF2α/ATF4/CHOP/GPX4 signaling pathway. Overall, this study provides novel insights into DDT’s protective mechanisms against ICH-induced neuronal injury by modulating ferroptosis and ERS pathways, underscoring its potential as an effective therapeutic strategy.

Titanium dioxide nanoparticles (TiO2-NPs) released into the environment is becoming more prevalent due to their increased usage, marine TiO2-NPs contamination is escalating concerns in coastal areas. To understand the potential impact of TiO2-NPs on transcript changes in pearl oyster (Pinctada fucata martensii), transcriptome analysis on the gill tissues of pearl oysters was conducted after 14-day TiO2-NPs exposure and 7-day brief recovery. A total of 911 differentially expressed genes (DEGs) were identified between the control group (TC) and the experimental group (TE) exposed to 14-day TiO2-NPs. Gene ontology (GO) analyses of the DEGs demonstrated their substantial enrichments in functions related to “hydrolase activity”, “oxidoreductase activity”, and “DNA integration”. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses of the DEGs indicated enrichment in several pathways, including “ubiquitin-mediated protein hydrolysis”, “ECM-receptor interactions”, “NOD-like receptor signaling pathway”, “Toll-like receptor”, and “FOXO signaling pathway”. This suggests that exposure to TiO2-NPs intensifies oxidative stress and apoptosis in pearls oysters, leading to negative effects such as disrupted protein homeostasis, decreased biomineralization activity, reduced neuronal excitability, weakened immune response, and reduced cellular metabolism. Transcriptome analysis identified 844 DEGs between the TE and recovery group (TR), which underwent a 7-day brief recovery period. GO analyses of the DEGs demonstrated their substantial enrichments in functions related to “DNA integration”, “obsolete oxidation-reduction process”, and “proteolysis”. KEGG pathways analyses of the DEGs indicated enrichment in several pathways, including “lysine degradation”, “glycine, serine, and threonine metabolism”, and “NOD-like receptor signaling pathway”. The findings indicated that although pearl oysters showed only slight relief after 7 days of brief recovery, they continued to experience negative effects from TiO2-NP exposure. Our findings shed light on the complex responses of pearl oysters to TiO2-NPs stress and offer valuable theoretical insights into the toxicological impact of TiO2-NPs on pearl oysters.

The incidence of chronic wound healing is promoted by the growing trend of elderly population, obesity, and type II diabetes. Although numerous wound dressings have been studied over the years, it is still challenging for many wound dressings to perfectly adapt to the healing process due to the dynamic and complicated wound microenvironment. Aiming at an optimal reproduction of the physiological environment, multifunctional electrospinning nanofibrous membranes (ENMs) have emerged as a promising platform for the wound treatment owing to their resemblance to extracellular matrix (ECM), adjustable preparation processes, porousness, and good conformability to the wound site. Moreover, profiting from the booming development of human-machine interaction and artificial intelligence, a next generation of intelligent electrospinning nanofibrous membranes (iENMs) based wound dressing substrates that could realize the real-time monitoring of wound proceeding and individual-based wound therapy has evoked a surge of interest. In this regard, general wound-related biomarkers and process are overviewed firstly and representative iENMs stimuli-responsive materials are briefly summarized. Subsequently, the emergent applications of iENMs for the wound healing are highlighted. Finally, the opportunities and challenges for the development of next-generation iENMs as well as translating iENMs into clinical practice are evaluated.

Objective: This study aimed to estimate the effects of the volume of preperitoneal balloon (PPB) on arterial and venous hemorrhage in a swine pelvic fracture model.Methods: Twenty-four swine were randomized into 0-mL, 500-mL, 800-mL, and 1000-mL intra-hematoma PPB groups. They were subjected to open-book pelvic fracture and reproducible injuries in the external iliac artery and vein. The pelvic binder and IH-PPBs with different volumes of fluid were applied to control the active hemorrhage after arterial and venous injuries. The survival time and rate during 60-min observation and digital subtraction angiography (DSA) images were the primary endpoints in this study. Secondary endpoints included survival rate within 70 min, peritoneal pressure, hemodynamics, blood loss, infusion fluid, blood pH, and lactate concentration.Results: Our results indicated that the 800-mL and 1000-mL groups had a higher survival rate (0%, 50%, 100% and 100% for 0, 500, 800, and 1000-mL groups respectively; p < 0.0001) and longer survival time (13.83 ± 2.64, 24.50 ± 6.29, 55.00 ± 6.33, and 60.00 ± 0.00 min for 0, 500, 800, and 1,000 groups respectively; p < 0.0005) than the 0-mL or 500-mL groups during the 60 min observation. Contrastingly, survival rate and time were comparable between 800-mL and 1000-mL groups during the 60-min observation. The IH-PPB volume was associated with an increase in the pressure of the balloon and the preperitoneal pressure but had no effect on the bladder pressure. Lastly, the 1000-mL group had a higher mean arterial pressure and systemic vascular resistance than the 800-mL group.Conclusion: IH-PPB volume-dependently controls vascular bleeding after pelvic fracture in the swine model. IH-PPB with a volume of 800 mL and 1000 mL efficiently managed pelvic fracture-associated arterial and venous hemorrhage and enhanced survival time and rate in the swine model without evidences of visceral injury.

Cancer and diabetes are significant diseases that pose a threat to human health. Their interconnection is complex, particularly when they coexist, often necessitating multiple therapeutic approaches to attain remission. Sodium-glucose cotransporter protein two inhibitors (SGLT-2i) emerged as a treatment for hyperglycemia, but subsequently exhibited noteworthy extra-glycemic properties, such as being registered for the treatment of heart failure and chronic kidney disease, especially with co-existing albuminuria, prompting its assessment as a potential treatment for various non-metabolic diseases. Considering its overall tolerability and established use in diabetes management, SGLT-2i may be a promising candidate for cancer therapy and as a supplementary component to conventional treatments. This narrative review aimed to examine the potential roles and mechanisms of SGLT-2i in the management of diverse types of cancer. Future investigations should focus on elucidating the antitumor efficacy of individual SGLT-2i in different cancer types and exploring the underlying mechanisms. Additionally, clinical trials to evaluate the safety and feasibility of incorporating SGLT-2i into the treatment regimen of specific cancer patients and determining appropriate dosage combinations with established antitumor agents would be of significant interest.

BackgroundPatients with age-related hearing loss (ARHL) often struggle with tracking and locating sound sources, but the neural signature associated with these impairments remains unclear.Materials and methodsUsing a passive listening task with stimuli from five different horizontal directions in functional magnetic resonance imaging, we defined functional regions of interest (ROIs) of the auditory “where” pathway based on the data of previous literatures and young normal hearing listeners (n = 20). Then, we investigated associations of the demographic, cognitive, and behavioral features of sound localization with task-based activation and connectivity of the ROIs in ARHL patients (n = 22).ResultsWe found that the increased high-level region activation, such as the premotor cortex and inferior parietal lobule, was associated with increased localization accuracy and cognitive function. Moreover, increased connectivity between the left planum temporale and left superior frontal gyrus was associated with increased localization accuracy in ARHL. Increased connectivity between right primary auditory cortex and right middle temporal gyrus, right premotor cortex and left anterior cingulate cortex, and right planum temporale and left lingual gyrus in ARHL was associated with decreased localization accuracy. Among the ARHL patients, the task-dependent brain activation and connectivity of certain ROIs were associated with education, hearing loss duration, and cognitive function.ConclusionConsistent with the sensory deprivation hypothesis, in ARHL, sound source identification, which requires advanced processing in the high-level cortex, is impaired, whereas the right–left discrimination, which relies on the primary sensory cortex, is compensated with a tendency to recruit more resources concerning cognition and attention to the auditory sensory cortex. Overall, this study expanded our understanding of the neural mechanisms contributing to sound localization deficits associated with ARHL and may serve as a potential imaging biomarker for investigating and predicting anomalous sound localization.

Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer (P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaric acid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effects of P. ginseng phenolic acid monomers on melanin production were assessed. Methods: In vitro and in vivo impact of phenolic acid monomers were assessed. Results: SA, PA, p-CA and VA inhibited tyrosinase (TYR) to reduce melanin production, whereas CA had the opposite effects. SA, PA, p-CA and VA significantly downregulated the melanocortin 1 receptor (MC1R), cycle AMP (cAMP), protein kinase A (PKA), cycle AMP-response element-binding protein (CREB), microphthalmia-associated transcription factor (MITF) pathway, reducing mRNA and protein levels of TYR, tyrosinase-related protein 1 (TYRP1), and TYRP2. Moreover, CA treatment enhanced the cAMP, PKA, and CREB pathways to promote MITF mRNA level and phosphorylation. It also alleviated MITF protein level in α-MSH-stimulated B16F10 cells, comparable to untreated B16F10, increasing the expression of phosphorylation glycogen synthase kinase 3β (p-GSK3β), β-catenin, p-ERK/ERK, and p-p38/p38. Furthermore, the GSK3β inhibitor promoted p-GSK3β and p-MITF expression, as observed in CA-treated cells. Moreover, p38 and ERK inhibitors inhibited CA-stimulated p-p38/p38, p-ERK/ERK, and p-MITF increase, which had negative binding energies with MC1R, as depicted by molecular docking. Conclusion: P. ginseng roots' phenolic acid monomers can safely inhibit melanin production by bidirectionally regulating melanin synthase transcription. Furthermore, they reduced MITF expression via MC1R/cAMP/PKA signaling pathway and enhanced MITF post-translational modification via Wnt/mitogen-activated protein kinase signaling pathway.

Owing to the presence of drugs targeting adrenergic receptors in aquatic ecosystems, considerable attention has been directed towards their environmental distribution and fate in recent decades. However, their potential impacts on non-target aquatic organisms, particularly fish, have received relatively limited investigation. In this study, moxisylyte (MOX) and propranolol (PRO) were selected as representatives of α- or β-adrenergic receptor antagonist, respectively, and we assessed their effects on the early life stages of zebrafish, especially on the nervous and cardiovascular systems. Although both compounds exhibited marginal effects on zebrafish survival, hatching and gross abnormality following exposure to concentrations ranging from 1 to 625 μg/L, they adversely affected the development of cardiovascular and nervous systems, but through different mechanisms of action, as evidenced by variations in gene transcriptional responses and enzyme activities. Notably, cardiovascular responses appear promising for use as potential biomarkers for exposure to drugs targeting adrenergic receptors. This study enhances our understanding of the ecotoxicological risks posed by α- and β-blockers in fish. Nonetheless, further investigation is needed to elucidate the precise mechanisms underlying the impacts of drugs targeting adrenergic receptors due to our limited knowledge of the physiological functions of the adrenergic system in fish.

This paper focuses on the selection and application of scale inhibitor by studying the problem of pipeline scaling in geothermal well development. Adding scale inhibitor can effectively reduce the treatment cost and achieve a good scale resistance effect, but the commonly used polyaspartic acid scale inhibitor has problems such as poor scale inhibition effect and large use limitations. Therefore, a new modified polyaspartic acid scale inhibitor (His-Tyr-SA-PASP) was prepared using polysuccinimide (PSI) as the raw material and histidine (His), tyrosine (Tyr), and sulfonic acid (SA) as the modification reagent. When the dosage of His-Tyr-SA-PASP was 8 mg/L, the scale inhibition rate of CaCO3 was 94.40%. In addition, the scale inhibition effect of His-Tyr-SA-PASP on CaCO3 was better than that of PASP. At the same time, under the condition of a static experiment at 75 °C, according to the ion concentration of water samples in different scale zones, this paper also identified the ratio of four composite scale inhibitors. When the dosage of compound scale inhibitor was 100 mg/L, Sodium of Polyaspartic Acid–Diethylene Triamine Penta (Methylene Phosphonic Acid)–2-Phosphonobutane-1,2,4-Tricarboxylic Acid–Amino Trimethylene Phosphonic Acid–Copolymer of Maleic and Acrylic Acid = (10:10:5:1:9), (15:10:5:2.5:2.5), (12.5:5:10:1:6.5), and (15:5:10:4:1) and the scale inhibition rate was more than 95%. Under the condition of a dynamic experiment, the optimized composite scale inhibitor still showed a scale inhibition rate of more than 90%. It provides a useful reference for the practical application of water treatment in geothermal wells and has the prospect of industrial application.

Enhanced denitrification has been reported under weak electric fields. However, it is difficult to investigate the mechanism of enhanced denitrification due to the complex interspecific interactions of mixed-culture systems. In this study, Pseudomonas stutzeri, capable of denitrification under anaerobic conditions, was selected for treating low COD/N (2.0, ratio between concentration of chemical oxygen demand and NO3−-N) artificial wastewater under constant external voltages of 0.2, 0.4, and 0.6 V. The results revealed that P. stutzeri exhibited the highest efficiency in nitrate reduction at 0.2 V. Moreover, the maximum nitrate removal rate was 15.96 mg/(L·h) among the closed-circuit groups, 19.39% higher than that under the open-circuit group. Additionally, a notable reduction in nitrite accumulation was observed under weak electric fields. Enzyme activity analysis showed that the nitrate reductase activities were significantly increased among the closed-circuit groups, while nitrite reductase activities were inhibited. Transcriptomic analysis indicated that amino acid metabolism, carbohydrate metabolism, and energy metabolism were increased, enhancing the resistance of P. stutzeri to environmental stress and the efficiency of carbon source utilization for denitrification. The current study examined the impacts of weak electric fields on enzyme activities and microbial metabolic pathways and offers valuable insights into the mechanism by which denitrification is enhanced by weak electric fields.

Abstract Cerebral ischemic stroke is a high-risk disease and imposes heavy burdens on patients in china. Acupuncture has been used for thousands of years to treat motor dysfunction, cognitive disorder and language barrier caused by cerebral ischemic stroke. Acupoint lines, vertex middle line and anterior oblique line of vertex temple, are always employed to treat cerebral ischemic stroke. However, the mechanism of the two acupoint lines in relieving cerebral ischemic stroke needs further exploration. In the present study, scalp acupuncture treatment alleviated the motor dysfunction, brain damage, and cell death induced by middle cerebral artery occlusion (MCAO) in rats. Proteomics analysis and ultrastructure observation indicated that endoplasmic reticulum and lysosomes might involve in the mechanism of the scalp acupuncture treatment in suppressing MCAO-triggered neural deficits. Effect of the scalp acupuncture treatment on ER stress was then investigated and found that the activation of ER stress mediators, including PERK, IRE1, and ATF6, was downregulated after the scalp acupuncture treatment. Co-localisation analysis of KDEL and CD63 showed that the engulfment of ER fragments by lysosomes was accelerated by the scalp acupuncture treatment. Moreover, expression of pro-apoptotic protein CHOP, phosphorylated-JNK, cleaved capases-3 and -9 also decreased after the scalp acupuncture. In conclusion, the present study showed that scalp acupuncture of vertex middle line and anterior oblique line of vertex temple may alleviate cerebral ischemic stroke by inhibiting ER stress-accelerated apoptosis.

The world is rich in coalbed methane (CBM) resources and has broad exploration and development prospects. In this paper, first, the technical difficulties of drilling and completion in deep shale formations in the Sichuan and Chongqing region is systematically summarized. Second, a systematic evaluation was conducted on the optimization of temperature resistance performance and trajectory control technology of the rotary guidance system. Third, evaluation and economic analysis were conducted on the experimental effects of different technologies. Results show that: (a) the optimization technology for temperature resistance performance of integrated high-temperature resistant guide head and surface cooling equipment has been formed, which can effectively reduce the circulation cooling time and improve drilling efficiency. (b) Real time measurement of underground engineering parameters and monitoring and evaluation of wellbore cleanliness can reduce drilling risks, while achieving quantitative evaluation of drilling fluid gas content. (c) Assisted by real-time optimization technology of mechanical drilling speed based on underground surface engineering parameters, the acceleration effect has been significantly improved.

Ferroptosis is a type of controlled cell death caused by lipid peroxidation, which results in the rupture of the cell membrane. ferroptosis has been repeatedly demonstrated over the past ten years to be a significant factor in a number of diseases. The liver is a significant iron storage organ, thus ferroptosis will have great potential in the treatment of liver diseases. Ferroptosis is particularly prevalent in HCC. In the opening section of this article, we give a general summary of the pertinent molecular mechanisms, signaling pathways, and associated characteristics of ferroptosis. The primary regulating mechanisms during ferroptosis are then briefly discussed, and we conclude by summarizing the development of a number of novel therapeutic strategies used to treat HCC in recent years. Ferroptosis is a crucial strategy for the treatment of HCC and offers new perspectives on the treatment of liver cancer.

Background: Ischemic stroke (IS) is a leading cause of long-term disability and even mortality, threatening people's lives. Yinao Fujian (YNFJ) formula is a Traditional Chinese Medicine formula that has been widely used to treat patients with IS. However, the molecular mechanism of YNFJ for the treatment of IS is still elusive. Our study aimed to explore the potential protective effect and the underlying mechanisms of YNFJ on IS using a network pharmacology approach coupled with experimental validation. Materials and methods: Effective compounds of YNFJ were collected from BATMAN-TCM and TCMSP databases, while IS targets were obtained from GeneCards, OMIM, TTD and DrugBank databases. The protein-protein interaction (PPI) network was constructed to further screen the hub targets of YNFJ in IS treatment. GO and KEGG enrichment analyses were used to identify the critical biological processes and signaling pathways of YNFJ for IS. Moreover, Nissl staining, HE, TTC staining and Tunel staining were used in the MCAO model to prove the neuroprotective effect of YNFJ. Oxidative damage, inflammatory factor release and related pathways were tested in MCAO rat model and hypoxia-induced BV2 cell model, respectively. Results: We found that YNFJ treatment significantly alleviated MCAO-induced nerve damage and apoptosis. Then, network pharmacology screening combined with literature research revealed IL6, TNF, PTGS2, NFKBIA and NFE2L2 as the critical targets in a PPI network. Moreover, the top 20 signaling pathways and biological processes associated with the protective effects of YNFJ on IS were enriched through GO and KEGG analyses. Further analysis indicated that NF-κB and Nrf2/HO-1 signaling pathways might be highly involved in the protective effects of YNFJ on IS. Finally, in vitro and in vivo experiments confirmed that YNFJ inhibited the release of inflammatory factors (IL-6 and TNF-α) and MDA content, and increased the activity of SOD. In terms of the mechanism, YNFJ inhibited the release of inflammatory factors by suppressing the NF-κB pathway and decreased the expression of iNOS and COX-2 to protect microglia from inflammation damage. In addition, YNFJ initiated the dissociation of Keap-1 and Nrf2, and activated the downstream protein HO-1, NQO1, thus decreasing oxidative stress. Conclusion: Taken together, the findings in our research showed that the protective effects of YNFJ on IS were mainly achieved by regulating the NF-κB and Nrf2/HO-1 signaling pathways to inhibit oxidative stress damage and inflammatory damage of microglia.

Objective: The spread of the novel SARS-Cov-2 variant Omicron created a challenging public health situation in a number of countries. In March 2022, Omicron emerged in Changchun, China, and the number of patients infected rapidly increased. The prevalence of Omicron infection symptoms differs from that of Delta, with more upper airway clinical symptoms apparent. This study aimed to investigate the clinical and upper airway characteristics of the Omicron variant. Materials and methods: In this retrospective study, we collected data from participants in Changchun who had tested positive for Omicron with quantitative polymerase chain reaction between 10 March and 30 May 2022 using telephone interviews. The questionnaire was designed by the research team based on the number of upper airway symptoms using the visual analogue scale. We also considered age, sex, vaccination status, general symptoms, and cure period. Results: A total of 3715 patients (2056 males and 1659 females) with mild COVID-19 from the Omicron variant were included. The patients had a mean age of 38.63 ( ± 13.97) years (range 2–86 years). The vaccine uptake rate was 91.33 % (8.66 %, 4.58 %, 65.33 %, and 21.43 % had received zero, one, two, and three doses, respectively). The incidence of upper airway symptoms, including throat and nasal symptoms, was 54.21 %. Throat symptoms were the most common during Omicron infection (49.12 %). Nasal symptoms were also common (20.08 %). The incidence of lower airway symptoms was 25.60 %, and gastrointestinal symptoms was 10.87 %. The incidence of general symptoms was 55.26 %. The cure period ranged from three to 37 days, with a mean of 10.24 ± 4.69 days. We compared the upper airway symptom severity for Omicron among different vaccination statuses and found no differences. Conclusions: The main clinical characteristics of the SARS-Cov-2 Omicron variant are upper airway symptoms and general symptoms. Fever remains the most common symptom, followed by mild dry cough. There was no association between Omicron infection and COVID-19 vaccines, and the vaccination status might have been ineffective against upper airway symptom severity by Omicron.

Abstract Methane seepage, generated from natural processes or gas hydrate dissociation, drives the development of cold seep ecosystems and leads to atmosphere methane emission, thereby influencing climate change. Uncovering the intrinsic interactions among methane seepage intensities, biogeochemical processes in the sediment, and benthic community characteristics at the seafloor is essential to clarify and predict the ultimate fate of methane leakage from the deep sea. Here, we conducted a systematic investigation of methane intensity, pore fluid migration characteristics, sediment mineral fraction features, and the evolution of biological communities in areas with different methane intensities. Furthermore, analyses of high‐resolution images, pore fluid geochemical feature, and lithologic characteristics of the sediment in the Haima cold seep were also carried out in this study. The results showed that, in areas with different methane intensities, organic matter sulfate reduction and anaerobic oxidation of methane were heterogeneous. The heterogeneity led to the methane transformation zones at different depths, which changed the mineral composition of the sediment and biological communities in the seabed. In addition, a hypothesis of successional sequence of biomes in cold seep was established. This study revealed that the methane seepage intensity was a key factor in determining the biogeochemical process in the sediment of cold seep. The coupling effects of biogeochemical processes and methane seepage intensities dominated the community succession of cold seep. These findings could provide important implications for understanding the dynamic deep marine methane cycle mechanism and the contribution of deep‐sea methane released to climate change.

Alzheimer's disease (AD) is a neurological condition that progresses with age. Amyloid-β (Aβ) aggregation has been suggested to be a key pathogenic process in Alzheimer's disease. Ginseng polysaccharides (GP), the main biologically active components isolated from Panax ginseng C. A. Meyer (ginseng), may act as neuroprotective agents with potential benefits for AD patients. However, GP effects on Aβ pathology and AD symptoms are still unclear. Here, a 4.7-kDa GP termed GP4 was purified and subjected to basic physicochemical characterization. The biological effects of GP4 to prevent Aβ aggregation were then assessed with cross-species AD models, including Aftin-5-treated SH-SY5Y cells and cerebral organoids, and transgenic C. elegans overexpressing the full-length human Aβ42 peptide. These analyses ultimately demonstrated that GP4 was capable of inhibiting Aβ accumulation both in vivo and vitro, and with early intervention of GP4 being sufficient to alleviate Aβ42-associated aging phenotypes and memory loss in C. elegans model of AD. Furthermore, neuroinflammation was significantly down-regulated in human cells and cerebral organoids. From a mechanistic perspective, the ability of GP4 to inhibit Aβ aggregation was found to be related to its ability to promote neuronal mitophagic activity. This finding offers a robust theoretical foundation for the further development of GP4 as a candidate drugs with the potential to treat AD.

Allergic rhinitis is a non-infectious chronic inflammatory disease of the nasal mucosa that affects T cells and their cytokines. T cells play significant roles in the development of allergic inflammatory diseases by orchestrating mechanisms underlying innate and adaptive immunity. Although many studies on allergic rhinitis have focused on helper T cells, molecular makeup, and pathogenesis-related transduction pathways, pathological mechanisms have not yet been completely explored. Recent studies have suggested that T cell status may play an important role in the interaction between T cells and the nasal mucosal barrier in allergic rhinitis. This study aimed to explore the interactions between T cells and nasal mucosal barriers in allergic rhinitis and to review the therapeutic modalities of pertinent biological agents involving T cells.

Chlorpyrifos is a widely used organophosphorus insecticide because of its high efficiency and overall effectiveness, and it is commonly detected in aquatic ecosystems. However, at present, the impact of chlorpyrifos on the aquatic micro-ecological environment is still poorly understood. Here, we established aquatic microcosm systems treated with 0.2 and 2.0 µg/L chlorpyrifos, and employed omics biotechnology, including metagenomics and 16S rRNA gene sequencing, to investigate the effect of chlorpyrifos on the composition and functional potential of the aquatic and zebrafish intestinal microbiomes after 7 d and 14 d chlorpyrifos treatment. After 14 d chlorpyrifos treatment, the aquatic microbial community was adversely affected in terms of its composition, structure, and stability, while its diversity showed only a slight impact. Most functions, especially capacities for environmental information processing and metabolism, were destroyed by chlorpyrifos treatment for 14 d. We observed that chlorpyrifos increased the number of risky antibiotic resistance genes and aggravated the growth of human pathogens. Although no clear effects on the structure of the zebrafish intestinal microbial community were observed, chlorpyrifos treatment did alter the metabolic capacity of the zebrafish. Our study highlights the ecological risk of chlorpyrifos to the aquatic environment and provides a theoretical basis for the rational use of pesticides in agricultural production.

Context Jiedutongluotiaogan formula (JTTF), a traditional Chinese medicine (TCM), could promote islet function. However, the potential effect of JTTF on endoplasmic reticulum stress (ERS) and autophagy have not been reported.Objective This study explores the potential effect of JTTF on ERS and autophagy in the pancreas.Materials and methods The Zucker diabetic fatty (ZDF) rats were randomised into five groups, control, model, JTTF (1, 3, 5 g/kg/day for 12 weeks). LPS induced pancreatic β-cells were treated with JTTF (50, 100, 200 μg/mL). LPS was used to induce pancreatic β-cell injury, with cell viability and insulin secretion evaluated using MTT, glucose-stimulated insulin secretion (GSIS) assays, and PCR. Intracellular Ca2+ concentration was measured using flow cytometry, while ERS and autophagy levels were monitored via Western blotting and/or immunostaining.Results Compared with the model group, body weight, FGB, HbA1c, IPGTT, FINs, and HOMA-IR in JTTF treatment groups were significantly reduced. In islets cells treated with JTTF, the pancreatic islet cells in the JTTF group were increased, lipid droplets were reduced, and there was a decrease in Ca2+ (16.67%). After JTTF intervention, PERK, p-PERK, IRE1α, p- IRE1α, ATF6, eIF2α, GRP78, p-ULK1, LC3 and p62 expression decreased, whereas Beclin1and p-mTOR expression increased. In addition, the expression of proteins related to apoptosis in the JTTF groups were lower than those in the control group.Discussion and conclusions JTTF may alleviate pancreatic β-cell injury by inhibiting ER stress and excessive autophagy in diabetic rats. This provides a new direction for treating diabetes and restoring pancreatic dysfunction by TCM.

Background: Aerobic cellular respiration provides chemical energy, adenosine triphosphate (ATP), to maintain multiple cellular functions. Sirtuin 1 (SIRT1) can deacetylate peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) to promote mitochondrial biosynthesis. Targeting energy metabolism is a potential strategy for the prevention and treatment of various diseases, such as cardiac and neurological disorders. Ginsenosides, one of the major bioactive constituents of Panax ginseng, have been extensively used due to their diverse beneficial effects on healthy subjects and patients with different diseases. However, the underlying molecular mechanisms of total ginsenosides (GS) on energy metabolism remain unclear. Methods: In this study, oxygen consumption rate, ATP production, mitochondrial biosynthesis, glucose metabolism, and SIRT1-PGC-1α pathways in untreated and GS-treated different cells, fly, and mouse models were investigated. Results: GS pretreatment enhanced mitochondrial respiration capacity and ATP production in aerobic respiration-dominated cardiomyocytes and neurons, and promoted tricarboxylic acid metabolism in cardiomyocytes. Moreover, GS clearly enhanced NAD+-dependent SIRT1 activation to increase mitochondrial biosynthesis in cardiomyocytes and neurons, which was completely abrogated by nicotinamide. Importantly, ginsenoside monomers, such as Rg1, Re, Rf, Rb1, Rc, Rh1, Rb2, and Rb3, were found to activate SIRT1 and promote energy metabolism. Conclusion: This study may provide new insights into the extensive application of ginseng for cardiac and neurological protection in healthy subjects and patients.

ABSTRACT Benefiting from the rapid developments and wide applications of high-throughput sequencing, great advancements have been made in investigating microbiota, which are highly diverse and play key roles in both element cycling and the energy flow of ecosystems. There have been inherent limitations of amplicon sequencing that could introduce uncertainty and raise concerns about the accuracy and reproducibility of this technology. However, studies focusing on the reproducibility of amplicon sequencing are limited, especially in characterizing microbial communities in deep-sea sediments. To evaluate reproducibility, 118 deep-sea sediment samples were used for 16S rRNA gene sequencing in technical replicates (repeated measurements of the same sample) that demonstrate the variability of amplicon sequencing. The average occurrence-based overlaps were 35.98% and 27.02% between two and among three technical replicates, respectively, whereas their abundance-based overlaps reached 84.88% and 83.16%, respectively. Although variations of alpha and beta diversity indices were found between/among technical replicates, alpha diversity indices were similar across samples, and the average beta diversity indices were much smaller for technical replicates than among samples. Moreover, clustering methods (i.e., operational taxonomic units [OTUs] and amplicon sequence variants [ASVs]) were shown to have little impact on the alpha and beta diversity patterns of microbial communities. Taken together, although there are variations between/among technical replicates, amplicon sequencing is still a powerful tool with which to reveal diversity patterns of microbiota in deep-sea sediments. IMPORTANCE The reproducibility of amplicon sequencing is vital for whether the diversities of microbial communities could be accurately estimated. Thus, reproducibility influences the drawing of sound ecological conclusions. Nevertheless, few studies have focused on the reproducibility of microbial communities that are characterized by amplicon sequencing, and studies focusing on microbiota in deep-sea sediments have been especially lacking. In this study, we evaluated the reproducibility of amplicon sequencing targeting microbiota in deep-sea sediments of cold seep. Our results revealed that there were variations between/among technical replicates and that amplicon sequencing was still a powerful tool with which to characterize the diversities of microbial communities in deep-sea sediments. This study provides valuable guidelines for the reproducibility evaluation of future work in experimental design and interpretation.

ABSTRACT To understand the molecular evolution of human parainfluenza virus type 2 (HPIV2), 21 Hemagglutinin-Neuraminidase (HN) gene sequences covering seven Chinese provinces in 2011 and 2017 to 2021 were combined with 90 published HN sequences worldwide for phylogenetic analysis. The result showed that global HPIV2 could be classified into two distinct clusters (I and II), five lineages (IA to IIE), and four sublineages (IB1 and 2, and IIE1 and 2). The minimum genetic distances between different clusters and lineages were 0.049 and 0.014, respectively. In the last decade, one lineage (IID) and three sublineages (IB1, IB2, and IIE1) have been cocirculating in China, with the sublineages IB2 and IIE1 dominating, while sublineages IB1 and IIE1 are dominant globally. In addition, the spread of HPIV2 had relative spatial clustering, and sublineage IB2 has only been detected in China thus far. The overall evolution rate of HPIV2 was relatively low, on the order of 10−4 substitutions/site/year, except for sublineage IB2 at 10−3 substitutions/site/year. Furthermore, human–animal transmission was observed, suggesting that the HPIV2 might have jumped out of animal reservoirs in approximately 1922, the predicted time of a common ancestor. The entire HN protein was under purifying/negative selection, and the specific amino acid changes and two novel N-glycosylation sites (N316 and N517) in sublineages IB1, IB2, and IIE1 were mostly located in the globular head region of the HN protein. In this study, preliminary evolutionary characteristics of HPIV2 based on the HN gene were obtained, increasing the recognition of the evolution and adaptation of HPIV2. IMPORTANCE The phylogenetic analysis showed that global HPIV2 could be classified into two distinct clusters (I and II) and five lineages (IA to IIE) with at least 0.049 and 0.014 genetic distances between clusters and lineages, respectively. Furthermore, lineages IB and IIE could be further divided into two sublineages (IB1-2 and IIE1-2). All China sequences belong to one lineage and three sublineages (IB1, IB2, IID, and IIE1), among which sublineages IB2 and IIE1 are predominant and cocirculating in China, while sublineages IB1 and IIE1 are dominant globally. The overall evolution rate of HPIV2 is on the order of 10−4 substitutions/site/year, with the highest rate of 2.18 × 10−3 for sublineage IB2. The entire HN protein is under purifying/negative selection, and the specific amino acid substitutions and two novel N-glycosylation sites (N316 and N517) in sublineages IB1, IB2, and IIE1 are mostly located in the globular head region of the HN protein.

Several per- and polyfluoroalkyl substances (PFAS) have been linked to metabolic disorders in organisms. However, few studies have considered their combined effects, which would be more representative of PFAS occurring in the environment. In this study, zebrafish embryos were exposed to a mixture of 18 PFAS at three environmentally relevant concentrations for 5 days to assess their bioconcentration and metabolic consequences. The burdens of ∑PFAS in zebrafish larvae were 0.12, 1.58, and 9.63 mg/kg in the 0.5, 5, and 50 μg/L treatment groups, respectively. Exposure to the PFAS mixture accelerated hatching and larval heart rates, increased energy expenditure, and reduced ATP levels and glucose contents due to decreased feed intake and glucose uptake. Metabolomic analysis revealed that exposure to the PFAS mixture enhanced glycolysis but inhibited phospholipid synthesis, and significantly increased the expression of lipid metabolism related genes (srebf1, acox, and pparα), which indicated enhanced β-oxidation. The significant changes in mitochondrial membrane potential, mitochondrial content, and the transcription of genes involved in the mitochondrial respiratory chain (mfn2, ndufs1, atp5fa1, and mt-nd1) and mitochondrial DNA replication and transcription (18rs-rrn, and polg1) suggested that exposure to the PFAS mixture could cause mitochondrial dysfunction and further disrupt glucose and lipid metabolic pathways, ultimately causing metabolic disorders in zebrafish larvae. These findings demonstrate the importance of assessing the metabolic effects of PFAS mixtures on early development in wildlife and humans.

Abstract Microplastic (MP) pollution is one of the greatest threats to marine ecosystems. Cold seeps are characterized by methane‐rich fluid seepage fueling one of the richest ecosystems on the seafloor, and there are approximately more than 900 cold seeps globally. While the long‐term evolution of MPs in cold seeps remains unclear. Here, how MPs have been deposited in the Haima cold seep since the invention of plastics is demonstrated. It is found that the burial rates of MPs in the non‐seepage areas significantly increased since the massive global use of plastics in the 1930s, nevertheless, the burial rates and abundance of MPs in the methane seepage areas are much lower than the non‐seepage area of the cold seep, suggesting the degradation potential of MPs in cold seeps. More MP‐degrading microorganism populations and functional genes are discovered in methane seepage areas to support this discovery. It is further investigated that the upwelling fluid seepage facilitated the fragmentation and degradation behaviors of MPs. Risk assessment indicated that long‐term transport and transformation of MPs in the deeper sediments can reduce the potential environmental and ecological risks. The findings illuminated the need to determine fundamental strategies for sustainable marine plastic pollution mitigation in the natural deep‐sea environments.

We conducted a study on the Trobriand Islands of Papua New Guinea (PNG) in 2018 to verify the safety and efficacy of the artemisinin-piperaquine (AP) mass drug administration (MDA) campaign in regions with moderate to high mixed malaria transmission. Based on the natural topography of the Trobriand Islands, 44,855 residents from 92 villages on the islands were enrolled and divided into the main and outer islands. Three rounds of MDA were conducted using grid-based management. The primary endpoint was the coverage rate. Adverse reactions, parasitemia, and malaria morbidity were the secondary endpoints. There were 36,716 people living in 75 villages on the main island, and the MDA coverage rate was 92.58–95.68%. Furthermore, 8,139 people living in 17 villages on the outer islands had a coverage rate of 94.93–96.11%. The adverse reactions were mild in both groups, and parasitemia decreased by 87.2% after one year of surveillance. The average annual malaria morbidity has decreased by 89.3% after the program for four years. High compliance and mild adverse reactions indicated that the MDA campaign with AP was safe. The short-term effect is relatively ideal, but the evidence for long-term effect evaluation is insufficient.

Poly(lactic acid) (PLA) and Poly(butylene succinate) (PBS) were chosen as raw materials and melt blended by a twin screw extruder and pelletized; then, the pellets were extruded into filaments; after that, various PBS/PLA blending samples were prepared by Fused Deposition Molding (FDM) 3D printing technology using the filaments obtained and the effect of the dosage of PBS on technological properties of 3D-printed specimens was investigated. For comparison, the PLA specimen was also prepared by FDM printing. The tensile strength, tensile modulus, thermal stability, and hydrophilicity became poorer with increasing the dosage of PBS, while the flexural strength, flexural modulus, impact strength, and crystallinity increased first and then decreased. The blend containing 10% PBS (10% PBS/PLA) had the greatest flexural strength of 60.12 MPa, tensile modulus of 2360.04 MPa, impact strength of 89.39 kJ/m2, and crystallinity of 7.4%, which were increased by 54.65%, 61.04%, 14.78%, and 51.02% compared to those of printed PLA, respectively; this blend also absorbed the least water than any other specimen when immersed in water. Different from the transparent PLA filament, 10% PBS/PLA filament presented a milky white appearance. The printed 10% PBS/PLA specimen had a smooth surface, while the surface of the printed PLA was rough. All the results indicated that the printed 10% PBS/PLA specimen had good comprehensive properties, including improved mechanical properties, crystallization performance, and surface quality than PLA, as well as proper wettability and water absorption. The prominent conclusion achieved in this work was that 10% PBS/PLA should be an ideal candidate for biodegradable feedstock among all the PBS/PLA blends for FDM 3D printing.

A disease, known as citrus greening, is a major threat to the citrus industry. The objective of this study was to investigate the feasibility of rapid detection and improving the identification accuracy of citrus greening with visible and near-infrared spectra under spectral fusion. After we obtained the spectra of the collected citrus leaves and used the polymerase chain reaction for part of them, five types of samples were sorted out: slight, moderate, serious, nutrient deficiency, and normal. This study of spectral fusion was conducted on three levels as spectral data, characteristic, and model decision, and the identification capacity was tested using prediction samples. It was found that the effect of a least squares support vector machine model for feature-level fusion based on principal component analysis presented the best performance, while in the Lin_Kernel function; the accuracy was 100%, penalty coefficient γ was 0.09, and operation time was 0.66 s. It is better than the single spectral discriminant model. The results showed that the fusion of visible and near-infrared spectra was feasible for the nondestructive detection of citrus greening disease. This method is of great significance for the healthy development of the citrus industry, and provides important reference value for the application of spectral fusion in other fields.

Wood flour–poly(butylene succinate)–poly(lactic acid) biocomposite samples were prepared by fused-deposition-molding 3D-printing technology, and modifications with glycerol and a silane coupling agent (KH550) were carried out. The samples were then hydrothermally aged. Modification with glycerol and KH550 enhanced the hydrophilicity of the samples and increased their tensile strength. Hydrothermal aging clearly whitened the surfaces of all the samples and made them more hydrophobic. Meanwhile, their tensile properties and thermal stability became poor; a higher hydrothermal aging temperature affected the mechanical properties more negatively. The modified samples turned out to be more resistant to the hydrothermal aging, and modification with KH550 could improve the anti-hydrothermal aging properties of the samples better than that with glycerol, where the tensile properties and the cross-sectional morphologies of the fractured specimens were concerned. Generally, the effects of hydrothermal aging temperature on the physico-mechanical properties of the printed specimens were greater than those by hydrothermal aging time.

To overcome the interference of noise on the exploration effectiveness of the controlled-source electromagnetic method (CSEM), we improved the deep learning algorithm by combining the denoising convolutional neural network (DnCNN) with the residual network (ResNet), and propose a method based on the residual denoising convolutional neural network (ResDnCNN) and shift-invariant sparse coding (SISC) for denoising CSEM data. Firstly, a sample library was constructed by adding simulated noises of different types and amplitudes to high-quality CSEM data collected. Then, the sample library was used for model training in the ResDnCNN, resulting in a network model specifically designed for denoising CSEM data. Subsequently, the trained model was employed to denoise the measured data, generating preliminary denoised data. Finally, the preliminary denoised data was processed using SISC to obtain the final denoised high-quality data. Comparative experiments with the ResNet, DnCNN, U-Net, and long short-term memory (LSTM) networks demonstrated the significant advantages of our proposed method. It effectively removed strong noise such as Gaussian, impulse, and square wave, resulting in an improvement of the signal-to-noise ratio by nearly 20 dB. Testing on CSEM data from Sichuan Province, China, showed that the apparent resistivity curves plotted using our method were smoother and more credible.

Background: Ginsenosides (GS) have potential value as cosmetic additives for prevention of skin photoaging. However, their protective mechanisms against skin barrier damage and their active monomeric constituents are unknown. Methods: GS monomer types and their relative proportions were identified. A UVB-irradiated BALB/c hairless mouse model was used to assess protective effects of GS components on skin epidermal thickness and transepidermal water loss (TEWL). Skin barrier function, reflected by filaggrin (FLG), involucrin (IVL), claudin-1 (Cldn-1), and aquaporin 3 (AQP3) levels and MAPK phosphorylation patterns, were analyzed in UVB-irradiated hairless mice or HaCaT cells. Results: Total GS monomeric content detected by UPLC was 85.45% and was largely attributed to 17 main monomers that included Re (16.73%), Rd (13.36%), and Rg1 (13.38%). In hairless mice, GS ameliorated UVB-induced epidermal barrier dysfunction manifesting as increased epidermal thickness, increased TEWL, and decreased stratum corneum water content without weight change. Furthermore, GS treatment of UVB-irradiated mice restored protein expression levels and epidermal tissue distributions of FLG, IVL, Cldn-1, and AQP3, with consistent mRNA and protein expression results obtained in UVB-irradiated HaCaT cells (except for unchanging Cldn-1 expression). Mechanistically, GS inhibited JNK, p38, and ERK phosphorylation in UVB-irradiated HaCaT cells, with a mixture of Rg2, Rg3, Rk3, F2, Rd, and Rb3 providing the same protective MAPK pathway inhibition-associated upregulation of IVL and AQP3 expression as provided by intact GS treatment. Conclusion: GS protection against UVB-irradiated skin barrier damage depends on activities of six ginsenoside monomeric constituents that inhibit the MAPK signaling pathway.

Floating offshore wind power, an emerging technology in the offshore wind industry, has attracted increasing attention for its potential to cooperate with other renewable energies to decarbonize energy systems. The environmental effects of the floating offshore wind farm in deep-sea areas should be considered, and methods to enhance the low-carbon effect should be devised. There have been a few studies assessing the environmental effects of the floating offshore wind farm, but the scales of these studies were relatively small. This study evaluated the environmental impacts of a floating wind farm with 100 wind turbines of 6.7 MW using life cycle assessment (LCA) method, based on the Chinese core life cycle database. Results showed that the carbon footprint of the wind farm was 25.76 g CO2-eq/kWh, which was relatively low in terms of global warming potential. Additionally, the floating offshore wind farm contributed most to eutrophication potential. A ± 20% variation in steel resulted in a ±3% to ±15% variation in the indicator score of each environmental category, indicating that the environmental performance of the wind farm was mainly influenced by this parameter. Moreover, scenario analysis showed that electric arc furnace routes can reduce the cumulative greenhouse gas emissions from upstream process of the floating offshore wind farm by 1.75 Mt CO2-eq by 2030. Emission reduction of the steel industry will further reduce the carbon footprint of the floating offshore wind farm. In the future, more baseline data need to be collected to improve the reliability of LCA. The effects of the floating offshore wind farm on marine ecology and atmospheric physical characteristics remain to be investigated in depth.

The fracturing and filling technology is expected to meet the dual needs of production stimulation and sand control of unconsolidated sandstone reservoirs, but there is no clear guiding method for the optimization of construction parameters, which hinders its efficient development. In order to study the optimization technology of high-efficiency fracturing and packing parameters in loose sandstone, this paper takes a loose sandstone reservoir in Liaohe Oilfield as the research object and firstly studies the fracture initiation and extension laws of loose sandstone fracturing based on really well and formation data and takes this as a physical. The model explores the migration law of proppant under different working conditions. Research shows that (a) the layered fracturing is more likely to form a fracture shape that meets the dual needs of filling and production enhancement. (b) Increasing the viscosity of the sand-carrying fluid is conducive to the migration of proppant to the far end, and increasing the sand ratio will make the proppant more easily suspended in the fracture, but it is not conducive to remote migration. (c) Taking “increasing viscosity + increasing sand ratio in a small range” as the optimization idea, the ideal filling parameters are preferably 85 mPa∙s sand−carrying fluid viscosity+15%sand ratio. The field application results show that the daily oil production of three wells after adopting this optimization method is 2.5-3.4 times higher than that of the adjacent wells at the initial stage of production and after stable production.

Rhodiola crenulata (RC) and Rhodiola fastigiata (RF) are representative species of Rhodiola with well-accepted health benefits; the roots are the medicinal part. However, prior to this study, the differences in phytochemicals between these two species and different parts of the same species remained unclear. Using LC-ESI-MS/MS, HS-SPME-GC–MS, chemical and sensory analyses, volatile compounds and non-volatile compounds, and antioxidant activities of the roots of Rhodiola crenulata and Rhodiola fastigiata and four parts (roots, leaves, flowers, and above-ground stems) of RC were investigated. The volatile compounds and non-volatile compounds of RC roots exhibited upregulation overall compared to those of RF roots, and the odorousness, phenolic content, and antioxidant activity were more pronounced in the RC roots. The phenolic content and antioxidant activity of roots and leaves, alongside the odorousness of roots and flowers, were more significant among the four parts of RC, and the RC roots and RC flowers exhibited similar odorousness. Comparison of non-volatile differential metabolites between RC roots and RC leaves showed upregulations of saccharides and phospholipids, and minor upregulations of flavonoids and phenylpropanoids in the roots; in addition, amino acids, organic acids, and vitamins were upregulated in the leaves. These results revealed the following: 1) RC roots are superior to RF roots regarding volatile compounds and non-volatile compounds, and antioxidant activity; 2) it is more favorable to select RC roots for exploiting volatile compounds compared with RC flowers in consideration of the biomass available; 3) in terms of non-volatile compounds, and antioxidant ability, RC leaves are also of great value in addition to RC roots, though these two parts show distinct characteristics.

With the widespread use of abamectin in agriculture, there is increasing urgency to assess the effects of abamectin on soil microorganisms. Here, we treated plant–soil microcosms with abamectin at concentrations of 0.1 and 1.0 mg/kg and quantified the impacts of abamectin on bulk and rhizosphere soil microbial communities by shotgun metagenomics after 7 and 21 days of exposure. Although abamectin was reported to be easily degradable, it altered the composition of the soil microbial communities, disrupted microbial interactions, and decreased community complexity and stability after 7 days of exposure. After treatment with abamectin at a concentration of 1.0 mg/kg, some opportunistic human diseases, and soil-borne pathogens like Ralstonia were enriched in the soil. However, most ecological functions in soil, particularly the metabolic capacities of microorganisms, recovered within 21 days after abamectin treatment. The horizontal and vertical gene transfer under abamectin treatments increased the levels of antibiotic resistance genes dissemination. Overall, our findings demonstrated the negative effects of abamectin on soil ecosystems in the short-term and highlight a possible long-term risk to public and soil ecosystem health associated with antibiotic resistance genes dissemination.

Floral thermogenesis is coupled with odor emission in known thermogenic plants. It is widely accepted that elevation in floral temperature can help release of volatile organic compounds (VOCs). However, no information is available about whether floral thermogenesis is associated with VOC biosynthesis. Here, we used RNA-Sequencing (RNA-Seq) to draw a gene expression atlas of floral thermogenesis in Magnolia denudata and captured an upregulation of Alternative Oxidase (AOX) during floral thermogenesis. Western blot analyses also suggested upregulation of AOX during floral thermogenesis. Moreover, oxygen consumption analyses revealed increased activity of the AOX respiration pathway during floral thermogenesis. Using HPLC analyses, we further found that increased AOX respiration substantially promoted production of citric acid by 1.35 folds, which provided fundamental metabolite skeletons for biosynthesis of VOCs. RNA-Seq also showed upregulation of genes regulating lignin catabolism, which was in agreement with in situ Raman chemical imaging of lignin. Taken together, our results suggest the central role of AOX by coupling heat production and VOC biosynthesis in floral thermogenesis of M. denudata.

Drug-eluting bead transarterial chemoembolization (DEB-TACE) has been widely used in the treatment of liver cancer; however, the utilization rate of chemotherapeutic drugs after embolization is low. Chemotherapy resistance mediated by high nuclear factor E2-related factor 2 (NRF2) expression limits DEB-TACE efficacy. Camptothecin (CPT), an NRF2 inhibitor, exerts chemosensitizing effects. We designed a controlled experiment to determine the efficacy and feasibility of DEB-TACE combined with CPT for the treatment of rabbit VX2 hepatoma. DEB-TACE activated NRF2 expression in the tumor region. NRF2 activation could be inhibited by the combined use of CPT. After DEB-TACE alone, the tumor necrosis was incomplete, there were still highly active tumor residues, and the apparent diffusion coefficient (ADC) value, which was negatively correlated with tumor activity observed by magnetic resonance imaging, remained low. After DEB-TACE combined with CPT, the relative necrosis of the tumor was more complete, the ADC value was higher, and the ADC change was greater. The single application of CPT did not result in evident liver function and physical burden to the rabbits. The combined use of CPT and DEB-TACE did not significantly increase DEB-TACE imaging of liver function and body. In conclusion, CPT can also inhibit high NRF2 expression after DEB-TACE treatment. Combining CPT with DEB-TACE can improve the sensitivity of DEB-TACE in the treatment of VX2 tumors, improve the therapeutic effect, and has no evident toxic and side effects. This study explored the methods for enhancing the efficacy of DEB-TACE in liver cancer from a new perspective and performed model experiments, which provided a theoretical basis for future clinical treatment.

Lenvatinib plus transarterial chemoembolization (TACE)have become the first choice for patients with hepatocellular carcinoma (HCC) that are unsuitable for TACE. Sorafenib plus TACE therapy for patients with portal vein tumor thrombus (PVTT) achieved positive results. However, Lenvatinib plus TACE appeared to achieve a more advantageous result for these patients based on the phase 3 REFLECT trial. Both TACE and lenvatinib therapy have immune-stimulating effects, so would lenvatinib plus TACE and immune checkpoint inhibitors be an advantageous therapy for unresectable HCC (uHCC)? Thirteen articles from PubMed were explored to determine the efficacy and safety of lenvatinib plus TACE with or without PD-1 inhibitors therapy. Most of the adverse events (AEs) were manageable. Lenvatinib plus TACE therapy was superior to lenvatinib monotherapy with intermediate stage HCC especially beyond up-to-seven criterion and was superior to TACE monotherapy in patients with uHCC or sorafenib plus TACE therapy in patients with PVTT. Objective response rates (ORRs) of 53.1%–75%, median progression free survival (PFS) of 6.15–11.6 months, and median overall survival (OS) of 14.5–18.97 months were achieved in the lenvatinib plus TACE group. Levatinib plus TACE and PD-1 inhibitors achieved ORRs of 46.7% –80.6%, median PFS of 7.3–13.3 months, and median OS of 16.9–24 months. Control studies also confirmed the triple therapy was superior to lenvatinib plus TACE in patients with uHCC. Overall, the triple therapy is a promising treatment for patients with uHCC, including main PVTT and extrahepatic metastasis. Lenvatinib plus TACE therapy was also preferable for intermediate stage HCC beyond up-to-seven criterion and for patients with PVTT.

Allergy is considered a hyperreactive immune response. Oligosaccharide ingredients are often incorporated in dietary supplements to modulate immunity, with oligosaccharides in ginseng thought to exert beneficial immunoregulatory effects. Here, efficacy and mechanism of action of ginseng oligosaccharide extract (GSO) for alleviating allergy were explored. GSO reduced secretion of β-HEX, HIS and inflammatory factor after C48/80 stimulation, while also reducing foot swelling and Evans blue exudation. Moreover, GSO treatment reduced PLCβ1 expression, intracellular calcium concentration, and calmodulin kinase (CaMK) phosphorylation that inhibited phosphorylation of PKC, leading to reduced MAPKs and p-c-Fos phosphorylation levels without affecting p-c-Jun levels. Notably, GSO inhibited allergy-like responses both in vivo and in vitro to reduce synthesis of inflammatory factors through the PKC/MAPK/c-Fos signaling pathway and inhibit PLC/Ca2+/CaMK pathway activity to reduce release of inflammatory factors and histamine and prevent allergy-associated degranulation effects. Thus, GSO holds promise as a clinical treatment for use in alleviating allergic disorders.

Leaf senescence is a natural phenomenon that occurs during the aging process of plants and is influenced by various internal and external factors. These factors encompass plant hormones, as well as environmental pressures such as inadequate nutrients, drought, darkness, high salinity, and extreme temperatures. Abiotic stresses accelerate leaf senescence, resulting in reduced photosynthetic efficiency, yield, and quality. Gaining a comprehensive understanding of the molecular mechanisms underlying leaf senescence in response to abiotic stresses is imperative to enhance the resilience and productivity of crops in unfavorable environments. In recent years, substantial advancements have been made in the study of leaf senescence, particularly regarding the identification of pivotal genes and transcription factors involved in this process. Nevertheless, challenges remain, including the necessity for further exploration of the intricate regulatory network governing leaf senescence and the development of effective strategies for manipulating genes in crops. This manuscript provides an overview of the molecular mechanisms that trigger leaf senescence under abiotic stresses, along with strategies to enhance stress tolerance and improve crop yield and quality by delaying leaf senescence. Furthermore, this review also highlighted the challenges associated with leaf senescence research and proposes potential solutions.

Background: This study aims to describe clinical and diagnostic phenotype and identify pathogenic variants of a female with unknown causes of infertility.Methods: Clinical assessment was performed for the phenotype diagnosis. Whole-exome sequencing (WES) and the followed cDNA-PCR sequencing were applied to identify the pathogenic variant and investigate the potentially aberrant mRNA splicing event. The pathogenicity of the variant was analysed using multiple in silico prediction tools, including the 3D protein remodelling. Quantitative RT-PCR (qRT-PCR) was performed to measure PATL2 mRNA expression in the peripheral blood leukocytes of the proband and controls.Results: The proband was diagnosed with the female infertility due to oocyte germinal vesicle (GV) arrest. A novel homozygous splice site variant of PATL2 (NM_001145112.2, c.871-1G>A), inherited from her asymptomatic heterozygous parents, was detected by WES. Sequencing of cDNA amplification products demonstrated that this variant resulted in the exon 10 skipping and in-frame loss of 54 nucleotides in the PATL2 transcript. Quantitative RT-PCR suggested that the mutant transcript escape the mRNA degradation.Conclusion: We identified a novel pathogenic homozygous splice site of PATL2 (c.871-1G>A) underlying the oocyte GV arrest phenotype and elucidated its molecular mechanism. This study expands the variant spectrum of PATL2 and benefits our understanding of its genotype-phenotype correlations.

Aging ovaries caused diminished fertility and depleted steroid hormone level. Ginsenosides, the active ingredient in ginseng, had estrogen-like hormonal effects. Although ginsenosides were well known for their ability to alleviate many age-related degenerative diseases, the effect of ginsenosides on the decline in reproductive capability caused by aging, as well as the mechanism, are unknown. We found that ginsenosides improved the quantity and quality of the offspring, prolonged life and restored muscle ability in aged female Drosophila. In addition, ginsenosides inhibited ovarian atrophy and maintained steroid hormone 20-Hydroxyecdysone (20E) and juvenile-preserving hormone (JH)) levels. Ginsenosides activated ecdysteroid receptor (ECR) and increased the expression of the early transcription genes E74 and Broad (Br), which triggered steroid signaling pathway. Meanwhile, ginsenosides promoted JH biosynthesis by increasing the expression of Hydroxyl-methylglutaryl-CoA reductase (HMGR) and juvenile hormone acid O-methyltransferase (JHAMT). Subsequently, JH was bound to Methoprene Tolerant (Met) and activated the transcription of the responsive gene Kruppel Homolog 1 (Kr-h1), which coordinated with 20E signaling to promote the reproduction of aged female Drosophila. The reproductive capacity and steroid hormone levels were not improved and the steroid signaling pathway was not activated in ginsenoside-treated ECR knockout Drosophila. This suggested that ginsenosides played a role dependent on targeted ECR. Furthermore, 17 kinds of ginsenoside monomers were identified from the total ginsenosides. Among them, Rg1, Re and Rb1 improved the reproductive capacity and steroid hormone levels of aged female Drosophila, which has similar effects to the total ginsenoside. These results indicated that ginsenosides could enhance the reproductive capacity of aged female Drosophila by activating steroid signals dependent on nuclear receptor ECR. In addition, ginsenoside monomers Rg1, Rb1 and Re are the main active components of total ginsenosides to improve reproductive ability. This will provide strong evidence that ginsenosides had the potential to alleviate age-induced reproductive degradation.

Cleft lip and palate (CLP) is one of the most common craniofacial malformations. Overall, 40–80% of CLP patients have varying degrees of articulation problems after palatoplasty. Previous studies revealed abnormal articulation-related brain function in CLP patients. However, the association between articulation disorders and cortical structure development in CLP patients remains unclear. Twenty-six CLP adolescents (aged 5–14 years; mean 8.88 years; female/male 8/18), twenty-three CLP adults (aged 18–35 years; mean 23.35 years; female/male 6/17), thirty-seven healthy adolescents (aged 5–16 years; mean 9.89 years; female/male 5/16), and twenty-two healthy adults (aged 19–37 years; mean 24.41 years; female/male 19/37) took part in the experiment. The current study aims to investigate developmental changes in cortical structures in CLP patients with articulation disorders using both structural and functional magnetic resonance imaging (MRI). Our results reveal the distinct distribution of abnormal cortical structures in adolescent and adult CLP patients. We also found that the developmental pattern of cortical structures in CLP patients differed from the pattern in healthy controls (delayed cortical development in the left lingual gyrus (t = 4.02, cluster-wise p < 0.05), inferior temporal cortex (z = −4.36, cluster-wise p < 0.05) and right precentral cortex (t = 4.19, cluster-wise p < 0.05)). Mediation analysis identified the cortical thickness of the left pericalcarine cortex as the mediator between age and articulation function (partial mediation effect (a*b = −0.48), 95% confident interval (−0.75, −0.26)). In conclusion, our results demonstrate an abnormal developmental pattern of cortical structures in CLP patients, which is directly related to their articulation disorders.

Esketamine showed more potency, more rapid recovery from anesthesia, and less psychotomimetic side effects when compared with ketamine. However, the patients still experience psychotomimetic side effects of esketamine. In order to investigate whether midazolam can attenuate the esketamine-induced overactive behaviors and neuronal hyperactivities, midazolam 0, 40, 80, and 120 mg/kg combined with esketamine 50 mg/kg were administrated on Kunming mice to assess the behaviors changes during anesthesia. The indicators, including action time, duration of agitation before the sedation, duration of sedation, duration of loss of pedal withdrawal reaction (PWR), duration of loss of righting reaction (RR), duration of agitation during the recovery, and recovery time, were monitored for up to 3–4 h after intraperitoneal administration. The results demonstrated that midazolam 40, 80, and 120 mg/kg efficiently decreased the esketamine-induced overactive behaviors including ataxia, excitation, and catalepsy before sedation. Midazolam and esketamine synergically improved the anesthesia quality assessed by PWR and RR. However, even high doses of midazolam were not able to suppress the esketamine-induced psychotomimetic effects during the recovery.

Meckel syndrome (MKS), also known as the Meckel–Gruber syndrome, is a severe pleiotropic autosomal recessive developmental disorder caused by dysfunction of the primary cilia during early embryogenesis. The diagnostic criteria are based on clinical variability and genetic heterogeneity. Mutations in the MKS1 gene constitute approximately 7% of all MKS cases. Herein, we present a non-consanguineous couple with three abnormal pregnancies as the fetuses showed MKS-related phenotypes of the central nervous system malformation and postaxial polydactyly. Whole-exome sequencing identified two novel heterozygous mutations of MKS1: c.350C>A and c.1408-14A>G. The nonsense mutation c.350C>A produced a premature stop codon and induced the truncation of the MKS1 protein (p.S117*). Reverse-transcription polymerase chain reaction (RT-PCR) showed that c.1408-14A>G skipped exon 16 and encoded the mutant MKS1 p.E471Lfs*92. Functional studies showed that these two mutations disrupted the B9–C2 domain of the MKS1 protein and attenuated the interactions with B9D2, the essential component of the ciliary transition zone. The couple finally got a healthy baby through preimplantation genetic testing for monogenic disorder (PGT-M) with haplotype linkage analysis. Thus, this study expanded the mutation spectrum of MKS1 and elucidated the genetic heterogeneity of MKS1 in clinical cases.

The temperature state of outer space devices is influenced by the heat flow outside the space. Although traditional numerical simulation analysis methods are highly accurate, they are time-consuming and not conducive for researchers to quickly assess the effects of external heat flow variations and are difficult to apply to program optimization codes that require large-scale iterative calculations or to codes for on-board temperature control chips. This paper presents an analytical algorithm for heat transfer problems: The transfer function method is applied to the thermal control analysis of outer space equipment with a small computational effort and a simple and straightforward computational procedure. Although this analytical approach only considers a limited set of influencing parameters and the precision of the calculation cannot be compared with numerical methods, it can be applied to the early prediction of internal temperature changes caused by heat flow changes outside the modification of outer space devices, embedded in the optimization code of a design solution, or integrated into the code of an on-board temperature control chip with minimum computational effort. In general, the transfer function method is not suitable for solving the radiation term, whereas this paper excludes the radiation term from the time delay calculation based on the small time scale of the radiation term and solves the time delay of the internal temperature relative to the external surface temperature directly, whereas the amplitude decay of the internal temperature change relative to the external surface temperature fluctuation is solved by the steady-state method based on the long period of the external heat flow change. The practicality of the transfer function method in the design of thermal control of external space devices is evidenced by comparing the computational results with those of commercial software and experimental results.

Abstract In the vehicle turbocharger operating process, the diffusor walls are susceptible to oil droplet deposition. This deposition may cause deterioration in the diffusor flow performance, consequently resulting in the deterioration of compressor performance. In this paper, a three‐dimensional steady computational fluid dynamic (CFD) numerical investigation was performed to study droplet deposition on the walls of a centrifugal compressor diffusor. Firstly, the theoretical basis of oil droplet distribution and formation on the diffusor were presented. On the basis of these, the distribution rules of the capture efficiency and particle concentration for the diffusor were investigated considering six different droplet diameters (0.25 μm, 0.5 μm, 0.75 μm, 1.00 μm, 1.25 μm, 1.5 μm). The results indicate that the particle mass concentration on the hub side increased gradually, and the concentration on the shroud side decreased inversely. Furthermore, the area of high particle mass concentration focused on the small radius area of the hub side or at the downstream of the channel in the direction of the streamline. And the particle mass concentration on the shroud is equally distributed. Finally, the combination of turbulent diffusion and inertial theory was proposed to analyze the mentioned phenomenon, and the droplet deposition mechanisms on the centrifugal compressor diffusor were summarized.