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Abstract Tigecycline is a last-resort antibiotic to treat complicated infections caused by multidrug-resistant pathogens, while the emergence of plasmid-mediated tet(X) family severely compromises its clinical efficacy. Novel antimicrobial strategies not limited to new antibiotics in pharmaceutical pipeline are urgently needed. Herein, we reveal the metabolic disparities between tet(X)-negative and -positive E. coli, including distinct energy demand patterns under tigecycline exposure. In particular, the cysteine and methionine metabolism pathway is remarkably downregulated in tet(X)-positive bacteria. More importantly, we find that the addition of exogenous L-methionine (Met) effectively resensitizes tet(X)-positive pathogens to tigecycline. Our mechanistic analysis demonstrates that exogenous Met promotes intracellular tigecycline accumulation by upregulating bacterial proton motive force. Moreover, Met accelerates the conversion to S-adenosyl-L-methionine, an essential methyl donor, thereby enhancing 5mC methylation modification in the promoter region of tet(X4) gene and reducing its expression. Consistently, the potentiation of Met to tigecycline is abolished in tet(X4)-carrying E. coli Δdcm but restored in dcm-complementary bacteria, which encodes DNA-cytosine methyltransferase. In multiple animal models of infection, Met markedly potentiates the effectiveness of tigecycline against pathogenic E. coli and K. pneumoniae. Overall, this work highlights the therapeutic potential of Met in overcoming plasmid-mediated high-level tigecycline resistance, and provides a new paradigm to enhance antibiotic efficacy by harnessing cellular metabolic networks as well as epigenetic modifications.

Study of niche characteristics, species interactions and community connectivity along elevation gradients contributes to our understandings on species' spatial interactions and vicarious distribution pattern, and helps reveal congeneric species coexistence and formation mechanisms of species distribution boundaries. In this study, we conducted a field survey on five types of Quercus communities across six elevation belts ranging from 900 to 2300 m (a.s.l) on the north and south slopes of Qinling Mountains, where the north subtropical and warm temperate zones divide. We analyzed the importance values, niche widths, niche overlaps, competition, interspecific associations of the three dominant Quercus species, as well as community connectivity. The richness of tree layer in the vicarious distribution of Quercus communities was relatively low, with Pinus (Pinus armandii and Pinus tabuliformis) being the main associate species. The χ² test and Spearman analysis demonstrated a significant negative correlation between Pinus and Quercus. The nich widths of all three studied Quercus species were found to be wider in their core communities compared to their edge communities, pariticularly on the south slopes. The niche overlap of dominant species on the both slopes were at a relatively low level, while higher niche overlap observed on the north slopes compared to the south slopes. The elevation trend in niche overlap among dominant species was consistent with interspecific competition intensity. Compared to the core and upper edge areas, the Quercus communities in the lower edge area exhibited greater niche overlap and a higher proportion of interspecific competition. The resutlts of variance ratio (VR) and W statistic values indicated that the Quercus communities on the both slopes primarily exhibited a non-significant negative correlation. The associations among dominant species were weak, resulting in a relatively loose community structure. Overall, the communities were in a relatively stable stage of middle-late succession. For the conservation and restoration process of Quercus forests, appropriate artificial interventions should be implemented to adjust interspecific relationships and enhance the strength of interspecific connections.

Oncolytic viruses have emerged as a highly promising modality for cancer treatment due to their ability to replicate specifically within tumors, carry therapeutic genes, and modulate the immunosuppressive tumor microenvironment through various mechanisms. Additionally, they show potential synergy with immune checkpoint inhibitors. A study report indicates that from 2000 to 2020, 49.5% of oncolytic viruses were administered intratumorally and 35% intravenously during clinical trials. However, both administration methods face significant challenges, particularly with intravenous delivery, which encounters issues such as non-specific tissue uptake, neutralizing antibody responses, and antiviral effects mediated by various immune cells. Despite extensive research into the antiviral roles of CD8+ T cells and NK cells in oncolytic virus therapy, neutrophils—constituting approximately 50% to 70% of human peripheral blood leukocytes—have received relatively little attention. Neutrophils are the most abundant leukocyte subset in peripheral circulation, known for their phagocytic activity. Beyond their traditional roles in bacterial and fungal infections, emerging literature suggests that neutrophils also play a critical role in the body’s antiviral responses. Given the gaps in understanding the role of neutrophils in oncolytic virus therapy, this article reviews current literature on this topic. It aims to provide a theoretical foundation for developing oncolytic virus-based cancer therapies and enhancing their anti-tumor efficacy in future clinical treatments.

Abstract Creep is the macroscopic manifestation of the process of generation, expansion, and penetration of microscopic cracks in a rock body. In this study, the GDEM continuous–discontinuous numerical simulation software was used to model a rock body containing X-fractured for the purposes of exploring creep crack expansion and rupture in the rock body, analyzing the effects of various factors on X-fractured the rock body under the rule of change of the creep curve, and assessing the influences of the intersection angle of the fracture and other factors on the non-parallel fractured rock body on the creep rupture process. The results show that an X-fractured rock body exhibits a mixed tensile–shear damage mode, with tensile damage being the main type of damage. In the isotropic creep stage of a rock body with X-fractured , the steady-state creep rate initially increases and then decreases as the sub- fracture length increases, with the change of the fracture angle of the creep rate of the w-type; the sub-fracture length of h is 14 mm, the rock body is the first to enter into the accelerated creep stage, for the different fracture intersection angle of the rock body For the rock mass with different fracture angles, the time sequence of entering the accelerated creep stage is consistent with the creep rate; when the fracture intersection angle is 45°, and the sub-fracture length is 12 mm, the rock mass has the largest degree of fragmentation, which has a significant impact on the creep damage; after using a single variable processing, it is found that the fracture intersection angle, the sub-fracture length and other factors compared to the fracture intersection angle has a greater impact on the creep damage of the X-fractured rock body. This paper can provide theoretical basis and reference for the study of rock engineering creep damage law and mechanical properties of X-fractured rock body.

PurposeThis study aims to optimize neoadjuvant radiotherapy target area for locally advanced rectal cancer (LARC) patients undergoing total neoadjuvant therapy (TNT) by examining local recurrence patterns.Methods and materialsWe retrospectively analyzed the clinical data of rectal cancer patients who undergone local recurrence after surgery. Recurrence sites were categorized and compared with initial diagnosis imaging, focusing on visible and suspicious lesions.ResultsOf the 126 patients who met our criteria, 186 lesions were analyzed. Within these, 75.40% of cases (95/126) and 83.33% of lesions (155/186) were located within the pelvic cavity. Conversely, 3.97% of cases (5/126) and 3.33% of lesions (6/186) occurred outside the pelvic cavity. Additionally, 20.63% of cases (26/126) and 13.44% of lesions (25/186) were found in both regions. Recurrences were predominantly observed in mesenteric regions (MR) (40.86%, 76/186) and presacral regions (PR) (32.26%, 60/186). In addition, 86.51% of patients (109/126) had recurrent lesions in HRA and the suspected lesions areas. Further analysis showed that initial CEA levels and adjuvant therapy types were identified as independent predictors for recurrence in MR/PR and initially suspected lesions. 86.51% of patients had recurrent lesions in HRA and the suspected lesions areasConclusionThe MR, PR, and areas of initial suspicious lesions are high-risk zones for post-surgical recurrence of LARC. Exploratory study of involved-field irradiation (IFI) can be carried out in the context of TNT in LARC.

Summary: Preparation of perovskite solar cells (PSCs) with long-lasting passivation effectiveness is challenging. Here, we present a protocol for fabricating efficient and stable passivated perovskite solar cells. We describe steps for preparing the electron transporting layer (ETL) via chemical bath deposition and perovskite film. We then detail procedures for passivating the surface defects with excess terpyridine ligands and stability characterization. This protocol features a passivator-terpyridine whose passivation effect is independent of concentration, which greatly improves the durability of the passivation.For complete details on the use and execution of this protocol, please refer to Wang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

China has recently launched extensive marine ranching projects, highlighting the need for scientific evaluation of ecosystem structure and function to guide their development. This study established two energy flow models and an evaluation index system to assess the structure, function, carrying capacity, and ecological status of both a marine ranching ecosystem and a nearby control site in the Beibu Gulf. The results show that the ranching ecosystem outperformed the control ecosystem in terms of food chain length, system size, and ecological carrying capacity of economically important species. The ranching ecosystem was classified as “relatively good”, while the control ecosystem was deemed “relatively poor”, which may confirm the success of the ranching efforts. Mussels, large crabs, and scorpaenidae were identified as key species for stock enhancement based on their biomass potential. Scenario simulations using Ecosim, driven by biomass and fishing factors, indicate that stock enhancement strategies targeting MOB (mussels, oysters, and barnacles) significantly improved the ranching ecosystem, raising its status to “good”. However, the simulations also revealed that stock enhancement had limited effects on optimizing food web structure, system organization, and energy transfer efficiency, suggesting that a combination of strategies is necessary for further improvement.

Abrus cantoniensis Hance (ACH) is an ancient Chinese medicine herb known for its therapeutic effects. This study investigated the potential protective effect of ACH against carbon tetrachloride (CCl4)-induced liver damage in mice. Fifty (n= 50) ICR mice were grouped into five groups. CCl4 was intraperitoneally injected into different mice groups: AM (CCl4 induced), AD (ACH-treated with 25 mg/kg), AZ (ACH-treated with 50 mg/kg), and AG (ACH-treated with100mg/kg) after every three days for a total of 31 days. The control group was denoted as AC. Additionally, groups AD, AZ, and AG received daily doses of ACH via gavage throughout the study period. According to our findings, ACH administration prominently mitigated liver pathological lesions and the increased liver index induced by CCl4 in mice (p < 0.05). Treatment with ACH resulted in a dose-dependent recovery of GSH-px, SOD, and CAT activities (p < 0.001). Moreover, the levels of TNF-α, MDA, and ALT showed significanlty decreasing trends with various doses of ACH (p < 0.001). Furthermore, 16 S rRNA gene sequencing demonstrated that ACH increased the abundance of beneficial genera of Comoclathris, Aureobasidium, and Kazachstania while decreased the presence of pathogenic genera such as Sporobolomyces and Filobasidium. Additionally, ACH treatment ameliorated the changes in liver metabolism due to CCl4 and enhanced the beneficial liver metabolites. In conclusion, ACH shows potential in protecting the liver against oxidative stress and inflammation caused by CCl4 exposure, possibly through its effects on gut microbiota and liver metabolism. Therefore, the use of ACH may offer an effective approach for alleviating CCl4-induced liver injury.

Abstract Background Neural stem cells (NSCs), especially human NSCs, undergo cellular senescence characterized by an irreversible proliferation arrest and loss of stemness after prolonged culture. While compelling correlative data have been generated to support the oxidative stress theory as one of the primary determinants of cellular senescence of NSCs, a direct cause-and-effect relationship between the accumulation of oxidation-mediated damage and cellular senescence of NSCs has yet to be firmly established. Human SOD1 (hSOD1) is susceptible to oxidation. Once oxidized, it undergoes aberrant misfolding and gains toxic properties associated with age-related neurodegenerative disorders. The present study aims to examine the role of oxidized hSOD1 in the senescence of NSCs. Methods NSCs prepared from transgenic mice expressing the wild-type hSOD1 gene were maintained in culture through repeated passages. Extracellular vesicles (EVs) were isolated from culture media at each passage. To selectively knock down oxidized SOD1 in NSCs and EVs, we used a peptide-directed chaperone-mediated protein degradation system named CT4 that we developed recently. Results In NSCs expressing the hSOD1 from passage 5, we detected a significant increase of oxidized hSOD1 and an increased expression of biomarkers of cellular senescence, including upregulation of P53 and SA-β-Gal and cytoplasmic translocation of HMGB1. The removal of oxidized SOD1 remarkably increased the proliferation and stemness of the NSCs. Meanwhile, EVs derived from senescent NSCs carrying the wild-type hSOD1 contained high levels of oxidized hSOD1, which could accelerate the senescence of young NSCs and induce the death of cultured neurons. The removal of oxidized hSOD1 from the EVs abolished their senescence-inducing activity. Blocking oxidized SOD1 on EVs with the SOD1 binding domain of the CT4 peptide mitigated its toxicity to neurons. Conclusion Oxidized hSOD1 is a causal factor in the cellular senescence of NSCs. The removal of oxidized hSOD1 is a strategy to rejuvenate NSCs and to improve the quality of EVs derived from senescent cells.

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms. This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms. Ferroptosis is a classic regulatory mode of cell death. Extensive studies of regulatory cell death in Alzheimer's disease have yielded increasing evidence that ferroptosis is closely related to the occurrence, development, and prognosis of Alzheimer's disease. This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferroptosis in Alzheimer's disease. Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer's disease.

The accelerating spread of antibiotic resistance has significantly weakened the clinical efficacy of existing antibiotics, posing a severe threat to public health. There is an urgent need to develop novel antimicrobial alternatives that can bypass the mechanisms of antibiotic resistance and effectively kill multidrug-resistant (MDR) pathogens. Antimicrobial peptides (AMPs) are one of the most promising candidates to treat MDR pathogenic infections since they display broad-spectrum antimicrobial activities and are less prone to achieve drug resistance. In this study, we investigated the antibacterial capability and mechanisms of two machine learning-driven linear peptide compounds termed YI12 and FK13. We reveal that YI12 and FK13 exhibit broad-spectrum antibacterial properties against clinically significant bacterial pathogens, inducing no or minimal hemolysis in mammalian red blood cells. We further ascertain that YI12 and FK13 are resilient to heat and acid-base conditions, and exhibit susceptibility to hydrolytic enzymes and divalent cations under physiological conditions. Initial mechanistic investigations reveal that YI12 and FK13 compromise bacterial membrane integrity, leading to membrane potential dissipation and excessive reactive oxygen species (ROS) generation. Collectively, our findings highlight the prospective utility of these two cationic amphiphilic peptides as broad-spectrum antibacterial agents.

Edible mushroom products, encompassing both cultivated and wild varieties, are highly favored by consumers due to their rich nutritional profiles, including significant levels of proteins and amino acids. These mushrooms have extensive applications across the food, pharmaceutical, and cosmetic industries, making the edible mushroom industry a vital component of global poverty alleviation efforts. Taking China as an example, the country produces over 45 million tons of edible mushrooms annually, accounting for 94.01% of the world’s total production, thereby establishing itself as the leading global producer of edible mushrooms. However, alongside the rapid expansion of this industry, concerns have emerged regarding counterfeit products and incidents of poisoning resulting from the consumption of toxic wild mushrooms. As follows, to advance the development and integrity of the mushroom production and processing industry: (1) This study presents the situation of counterfeit edible mushrooms and elucidates the factors contributing to the production of fraudulent products from both subjective and non-subjective perspectives. (2) We provide a detailed introduction to 22 varieties of freshly cultivated edible mushrooms and commonly encountered wild edible mushrooms in the Chinese consumer market, proposing the application of DNA barcoding, environmental DNA analysis, and other technologies for the future authentication of counterfeit mushroom products. (3) Concurrently, we present an overview of mushroom poisoning incidents in China from 2010 to 2023, emphasizing the challenges in mitigating the risks associated with wild mushroom consumption and preventing food poisoning, thereby necessitating heightened consumer caution. (4) Finally, we offer four recommendations aimed at ensuring the healthy, stable, and sustainable growth of the edible mushroom industry.

Background: Meniere Disease is a clinical condition defined by hearing loss, tinnitus, and aural fullness symptoms, there are currently no any medications approved for its treatment. Objective: To determine whether taVNS as an adjunctive therapy could relieve symptoms and improve the quality of life in patients with Meniere disease. Methods: In this Single-center, single blind, randomized trial, participants were assigned to transcutaneous auricular vagus nerve stimulation (taVNS) group and sham taVNS group. The primary outcome measures comprised Tinnitus Handicap Inventory, Dizziness Handicap Inventory, Pure Tone Auditory, Visual analogue scale of aural fullness. Secondary outcome measures comprised the 36-Item Short Form Health Survey, video head impulse test, and the caloric test. Results: After 12 weeks, the THI (−11.00, 95%CI, −14.87 to −7.13; P < 0.001), DHI (−47.26, 95%CI, −50.23 to −44.29; P < 0.001), VAS of aural fullness (−2.22, 95%CI, −2.95 to −1.49; P

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C–X–C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE–DTX) as an anti-metastasis agent to treat breast cancer. CTCE–DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE–DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide–drug conjugates with synergistic anti-tumor efficacy.

The glutinous rice starch (GRS) regeneration process could lead to decreased product quality and shorter shelf life. The purpose of this study was to analyze the effect of an ethanol extract of tea (EET) on the regeneration properties of GRS. The microstructure of starch was determined via scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR) spectroscopy was used to determine the microstructure of starch-polyphenol molecular groups, an X-ray diffraction (XRD) instrument was used to determine the starch crystal structure, a differential scanning calorimeter (DSC) was used to determine the thermodynamic properties of starch, and the inhibitory effect of EET on GRS regeneration was comprehensively evaluated. The effect of EET on the in vitro digestion properties of GRS was also determined. The results showed that the addition of EET in GRS resulted in an increase in solubility and swelling power and a decrease in crystallinity and ΔHr. Compared to the control group, when retrograded for 10 days, the ΔHr of GRS with 1%, 2.5%, 5%, and 10% addition of EET decreased by 34.61%, 44.53%, 52.93%, and 66.79%, respectively. Furthermore, the addition of EET resulted in a decrease in the content of RDS and an increase in the content of SDS and RS in GRS. It was shown that the addition of EET could significantly inhibit the retrogradation of GRS, improve the processability, and prolong the shelf life of GRS products.

The ε4 allele of the lipoprotein E gene (APOE4) is the strongest genetic risk factor associated with sporadic Alzheimer's disease (sAD). While the neuronal cell type-specific function of APOE4 in connection with AD pathology remains understudied. Therefore, we generated an induced pluripotent stem cells (iPSCs) line from a 77-year-old female donor with ApoE4 genetic background. We reprogrammed peripheral blood mononuclear cells (PBMCs) with non-integrative Sendai viral vectors containing reprogramming factors. Established iPSCs showed the capability of pluripotency, three-germ differentiation in vitro with normal karyotype. Hence, the generated iPSC could be a powerful tool to conduct further studies of AD mechanisms.

Abstract Introduction Women living with HIV (WLWH) are more likely to develop cervical cancer. Screening and available healthcare can effectively reduce its incidence and mortality rates. We aimed to summarize the lifetime prevalence and adherence rate of cervical cancer screening among WLWH across low‐ and middle‐income countries (LMICs), and high‐income countries (HICs). Methods We systematically searched PubMed, Web of Science and Embase for studies published between database inception and 2 September 2022, without language or geographical restrictions. Those reporting the lifetime prevalence and/or adherence rate of cervical cancer screening among WLWH were included. Pooled estimates across LMICs and HICs were obtained using DerSimonian–Laird random‐effects models. When the number of eligible studies was greater than 10, we further conducted stratified analyses by the World Health Organization (WHO) region, setting (rural vs. urban), investigation year, screening method, type of cervical cancer screening programme, age and education level. Results Among the 63 included articles, 26 provided data on lifetime prevalence, 24 on adherence rate and 13 on both. The pooled lifetime prevalence in LMICs was 30.2% (95% confidence interval [CI]: 21.0–41.3), compared to 92.4% in HICs (95% CI: 89.6–94.6). The pooled adherence rate was 20.1% in LMICs (95% CI: 16.4–24.3) and 59.5% in HICs (95% CI: 51.2–67.2). Discussion There was a large gap in cervical cancer screening among WLWH between LMICs and HICs. Further analysis found that those in LMICs had higher lifetime prevalence in subgroups with urban settings, with older age and with higher education levels; and those in HICs had higher adherence in subgroups with younger age and with higher education levels. Conclusions Cervical cancer screening among WLWH falls considerably short of the WHO's goal. There should be continuous efforts to further increase screening among these women, especially those residing in the rural areas of LMICs and with lower education levels.

Abstract Gut microbiota‐mediated colonization resistance (CR) is crucial in protecting the host from intestinal infections. Sleep deprivation (SD) is an important contributor in the disturbances of intestinal homeostasis. However, whether and how SD affects host CR remains largely unknown. Here, it is shown that SD impairs intestinal CR in mice, whereas nicotinamide mononucleotide (NMN) supplementation restores it. Microbial diversity and metabolomic analyses suggest that gut microbiota and metabolite profiles in SD‐treated mice are highly shaped, whereas NMN reprograms these differences. Specifically, the altered gut microbiota in SD mice further incurs the disorder of secondary bile acids pool accompanied by a decrease in deoxycholic acid (DCA). Conversely, NMN supplementation retakes the potential benefits of DCA, which is associated with specific gut microbiota involved in primary bile acids metabolic flux. In animal models of infection, DCA is effective in preventing and treating bacterial infections when used alone or in combination with antibiotics. Mechanistically, DCA alone disrupts membrane permeability and aggravates oxidative damage, thereby reducing intestinal pathogen burden. Meanwhile, exogenous DCA promotes antibiotic accumulation and destroys oxidant–antioxidant system, thus potentiating antibiotic efficacy. Overall, this work highlights the important roles of gut microbiota and bile acid metabolism in the maintenance of intestinal CR.

Objective(s): This study was designed to investigate whether HBx-induced podocyte injury is related to the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and the specific mechanism of the oxidative stress pathway in hepatitis B virus-associated glomerulonephritis (HBV-GN).Materials and Methods: The HBx gene was overexpressed in renal podocytes to mimic HBV-GN. Podocyte morphology was observed under a scanning electron microscope. Reactive oxygen species (ROS) generation was detected by dichlorodihydrofluorescein diacetate (DCFH-DA) assay. The podocytes in each group were treated with Hoechst 33342 and subjected to immunofluorescence staining. Caspase-1 activity and LDH levels were assessed with a Caspase-1 Activity Assay Kit and an LDH ELISA Kit, respectively. The expression of all pyroptosis-related proteins was examined by Western blot analysis.Results: Pyroptosis-related proteins, including NLRP3, apoptosis-associated speck-like protein containing card (ASC), caspase-1, IL-1β, and IL-18 (P

Many algae respond to the CO2 limitation in seawater by inducing a CO2 concentrating mechanism (CCM) to obtain sufficient inorganic carbon to meet their photosynthetic needs, and Ulva sp. is a model population suitable for studying the ecological adaptability of macroalgae. As the dominant species of green tide disaster, Ulva sp. often faces strong inorganic carbon restriction due to its rapid growth and high population density and must have evolved a variety of carbon acquisition strategies, such as CCM, to overcome these limitations. This paper briefly summarizes the position and function of the important components of CCM (inorganic carbon transporters, carbonic anhydrase, Rubisco, and pyrenoid) and introduces several indexes suitable for evaluating the relative function of CCMs in macroalgae from the aspects of affinity between photosynthesis and Rubisco for CO2, and carbonic anhydrase inhibitor. The methods of judging the carbon sequestration pathway of Ulva sp., the CCM responses of diversity under different carbon sources, and the related genes that may be involved in the operation of CCMs were summarized. This work could provide a reference for revealing the CCMs of macroalgae and lay a foundation for further research on the inorganic carbon utilization strategy of the Ulva sp.

The blood–brain barrier (BBB) is of vital importance to the progression and prognosis of subarachnoid hemorrhage (SAH). The construction of a simple, sensitive, and accurate detection assay for measuring the biomarkers associated with BBB injury is still an urgent need owing to the complex pathogenesis of SAH and low expression levels of pathological molecules. Herein, we introduced surface-enhanced Raman scattering (SERS) label-embedded Fe3O4@Au core-shell nanoparticles as ideal SERS sensors for quantitative double detection of MMP-9 and occludin in SAH patients. Meanwhile, utilizing the SERS signals to dynamically estimate MMP-9 and occludin concentration in the rat SAH model is the first application in exploring the relationship of pathological MMP-9 and occludin molecular levels with neurobehavioral score. This method warrants reliable detection toward MMP-9 and occludin with a wide recognition range and a low detection limit in blood samples. Furthermore, the results monitored by the SERS assay exactly matched with those obtained through a traditional enzyme-linked immunosorbent assay (ELISA). The aforementioned results demonstrated this novel biosensor strategy has extensive application prospects in the quantitative measurement of multiple types of biomolecules in body fluid samples.

This study draws on the social identity approach (SIA), to examine how political elites (i.e., members of the 116 th United States Congress) communicated norms about mask-wearing on social media during the COVID-19 pandemic. Using Twitter data collected in 2020, we found that Republican members of Congress were significantly less likely to promote mask-wearing than Democratic members. We also observed some variations in norm-conforming behaviors among the members of each party. For Republicans, increased loyalty to the Trump leadership was significantly associated with a lower level of mask promotion. For Democrats, we found some evidence that loyalty to the party predicted higher levels of mask promotion. On the other hand, interactions with out-group members decreased adherence to party norms for both Republican and Democratic members of Congress. These findings allow us to better understand the social–psychological effects of party membership among political elites as well as the importance of leader–follower relationships and intergroup interactions.

Small heat shock proteins (sHSPs) are ubiquitous proteins present in all organisms. The sHSPs are not only upregulated under heat shock as well as other stresses but also are expressed in unstressed cells, indicating quite diverse functions of sHSPs. However, there is little known about the role of sHSPs in nodulation and nitrogen fixation in soybean. In this study, we cloned a candidate protein of sHSP, GmHSP17.1, from proteome of nodule and analyzed its function in soybean nodulation. We found that GmHSP17.1 was a cytosolic protein and preferentially expressed during nodule development. An overexpression of GmHSP17.1 in composite transgenic plants showed increases in nodule number, fresh weight, nodule size, area of infection cells, and nitrogenase activity, and subsequently promoted the content of nitrogen and growth of soybean plants. While GmHSP17.1 RNA interference (RNAi) lines showed significantly impaired nodule development and nitrogen fixation efficiency. Through liquid chromatography-tandem mass spectrometry (LC-MS/MS), GmRIP1 was identified as the first potential target of GmHSP17.1, and was shown to be specifically expressed in soybean nodules. The interaction between GmHSP17.1 and GmRIP1 was further confirmed by yeast-two hybrid (Y2H), bimolecular fluorescence complementation (BiFC) in vivo and pull-down assay in vitro. Furthermore, peroxidase activity was markedly increased in GmHSP17.1 overexpressed nodules and decreased in RNAi lines. As a result, the reactive oxygen species (ROS) content greatly decreased in GmHSP17.1 overexpression lines and increased in suppression lines. Taken together, we conclude that GmHSP17.1 plays an important role in soybean nodulation through interacting with GmRIP1. Our results provide foundation for studying the mechanism of nitrogen fixation and for the genetics improvement of legume plants.

This paper presents a coil-based liquid lens (CLL) with a mature and simple fabrication process. A tunable focal length is achieved by changing the liquid–liquid interface curvature using electrowetting on dielectric (EWOD). The lens cavity is a coil wound or stacked by a particular structure named EWOD wire, which is made by coating a soft insulating dielectric layer on a flexible conductive core. As a result, requirements for different lens designs can be achieved, and coating an insulating dielectric layer in complex cavities is not required. The optical performance of the CLL is measured with a clear aperture of 8 mm, which shows that the tunable range for the focal length is (−∞, −35 mm] ∪ [78 mm, +∞) at a voltage of 0–235 V, and the response time is less than 40 ms.

Wool is the critical textile raw material which is produced by the hair follicle of sheep. Therefore, it has important implications to investigate the molecular mechanism governing hair follicle development. Due to high cellular heterogeneity as well as the insufficient cellular, molecular, and spatial characterization of hair follicles on sheep, the molecular mechanisms involved in hair follicle development and wool curvature of sheep remains largely unknown. Single-cell RNA sequencing (scRNA-seq) technologies have made it possible to comprehensively dissect the cellular composition of complex skin tissues and unveil the differentiation and spatial signatures of epidermal and hair follicle development. However, such studies are lacking so far in sheep. Here, single-cell suspensions from the curly wool and straight wool lambskins were prepared for unbiased scRNA-seq. Based on UAMP dimension reduction analysis, we identified 19 distinct cell populations from 15,830 single-cell transcriptomes and characterized their cellular identity according to specific gene expression profiles. Furthermore, novel marker gene was applied in identifying dermal papilla cells isolated in vitro. By using pseudotime ordering analysis, we constructed the matrix cell lineage differentiation trajectory and revealed the dynamic gene expression profiles of matrix progenitors' commitment to the hair shaft and inner root sheath (IRS) cells. Meanwhile, intercellular communication between mesenchymal and epithelial cells was inferred based on CellChat and the prior knowledge of ligand–receptor pairs. As a result, strong intercellular communication and associated signaling pathways were revealed. Besides, to clarify the molecular mechanism of wool curvature, differentially expressed genes in specific cells between straight wool and curly wool were identified and analyzed. Our findings here provided an unbiased and systematic view of the molecular anatomy of sheep hair follicle comprising 19 clusters; revealed the differentiation, spatial signatures, and intercellular communication underlying sheep hair follicle development; and at the same time revealed the potential molecular mechanism of wool curvature, which will give important new insights into the biology of the sheep hair follicle and has implications for sheep breeding.

The accessibility of mountain tourist attractions is a prerequisite to enhancing the attractiveness of tourist attractions and driving the well-being of local residential areas, which increases people’s prosperity and the sustainable development of tourist attractions, and achieves the UN’s Sustainable Development Goals (SDGs). This paper focuses on the accessibility of typical mountainous areas in the Qinghai–Tibet Plateau, and uses the cost distance and OD distance methods under the guidance of core-edge theory to explore the changes of accessibility of traffic nodes, tourist attractions, and residents with the future enrichment of the traffic road network. The results show that: (1) The change in accessibility will highlight the location advantages of some tourist attractions, which can be prioritized in the context of similar tourist attractions; (2) Regional accessibility improvements require a combination of traffic modes to maximize impact; (3) Residents of different multi-core circles could choose various industrial development patterns based on the accessibility of tourist attractions and residential areas; (4) Group development according to the spatial location and accessibility of tourist attractions can facilitate the virtuous drive among tourist attractions, which achieves the goal of integrated tourism.

Diarrhea is one of the most commonly reported diseases in young farm animals. Escherichia coli (E. coli) F17 is one of the major pathogenic bacteria responsible for diarrhea. However, the pathogenicity of diarrhea in lambs involving E. coli F17 strains and how E. coli F17 infection modifies lambs’ intestinal microbiota are largely unknown. To evaluate diarrhea in newborn lambs with an infection of E. coli F17, 50 lambs were selected for challenge experiments and divided into four groups, namely, a high-dose challenge group, low-dose challenge group, positive control group, and negative control group. The E. coli F17 challenge experiments caused diarrhea and increased mortality in the experimental lamb population, with a higher prevalence (90%), mortality (35%), and rapid onset time (4–12 h) being observed in the high-dose challenge group than the results observed in the low-dose challenge group (75%, 10%, 6–24 h, respectively). After the challenge experiment, healthy lambs in the high-dose challenge group and severely diarrheic lamb in the low-dose challenge group were identified as lambs sensitive/resistant to E. coli F17 (E. coli F17 -resistant/-sensitive candidate, AN/SE) according to the histopathological detection. Results of intestinal contents bacteria plate counting revealed that the number of bacteria in the intestinal contents of SE lambs was 102~3-fold greater than that of the AN lambs, especially in the jejunum. Then, 16S rRNA sequencing was conducted to profile the intestinal microbiota using the jejunal contents, and the results showed that SE lambs had higher Lactococcus and a lower Bacteroidetes:Firmicutes ratio and intestinal microbiota diversity in the jejunum than AN lambs. Notably, high abundance of Megasphaera elsdenii was revealed in AN lambs, which indicated that Megasphaera elsdenii may serve as a potential probiotic for E. coli F17 infection. Our study provides an alternative challenge model for the identification of E. coli F17-sensitive/-resistant lambs and contributes to the basic understandings of intestinal microbiota in lambs with different susceptibilities to E. coli F17.

Background Nowadays, both customers and producers prefer thin-tailed fat sheep. To effectively breed for this phenotype, it is important to identify candidate genes and uncover the genetic mechanism related to tail fat deposition in sheep. Accumulating evidence suggesting that post-transcriptional modification events of precursor-messenger RNA (pre-mRNA), including alternative splicing (AS) and alternative polyadenylation (APA), may regulate tail fat deposition in sheep. Differentially expressed transcripts (DETs) analysis is a way to identify candidate genes related to tail fat deposition. However, due to the technological limitation, post-transcriptional modification events in the tail fat of sheep and DETs between thin-tailed and fat-tailed sheep remains unclear. Methods In the present study, we applied pooled PacBio isoform sequencing (Iso-Seq) to generate transcriptomic data of tail fat tissue from six sheep (three thin-tailed sheep and three fat-tailed sheep). By comparing with reference genome, potential gene loci and novel transcripts were identified. Post-transcriptional modification events, including AS and APA, and lncRNA in sheep tail fat were uncovered using pooled Iso-Seq data. Combining Iso-Seq data with six RNA-sequencing (RNA-Seq) data, DETs between thin- and fat-tailed sheep were identified. Protein protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were implemented to investigate the potential functions of DETs. Results In the present study, we revealed the transcriptomic complexity of the tail fat of sheep, result in 9,001 potential novel gene loci, 17,834 AS events, 5,791 APA events, and 3,764 lncRNAs. Combining Iso-Seq data with RNA-Seq data, we identified hundreds of DETs between thin- and fat-tailed sheep. Among them, 21 differentially expressed lncRNAs, such as ENSOART00020036299, ENSOART00020033641, ENSOART00020024562, ENSOART00020003848 and 9.53.1 may regulate tail fat deposition. Many novel transcripts were identified as DETs, including 15.527.13 (DGAT2), 13.624.23 (ACSS2), 11.689.28 (ACLY), 11.689.18 (ACLY), 11.689.14 (ACLY), 11.660.12 (ACLY), 22.289.6 (SCD), 22.289.3 (SCD) and 22.289.14 (SCD). Most of the identified DETs have been enriched in GO and KEGG pathways related to extracellular matrix (ECM). Our result revealed the transcriptome complexity and identified many candidate transcripts in tail fat, which could enhance the understanding of molecular mechanisms behind tail fat deposition.

Abstract Background IL-17A directly induces epithelial-mesenchymal transition (EMT) in alveolar epithelial cells. It could coordinate with cigarette smoke extract (CSE) to promote proliferation of bronchial epithelial cells. In this study, we aim to explore the direct effect of IL-17A and CSE on EMT in bronchial epithelial cells. Methods Bronchial epithelial cells were isolated from C57BL/6 mice, and cocultured with CSE or/and IL-17A. E-cadherin and Vimentin expressions in cells were detected using immunofluorescence staining. IL-17R expression was detected using immunohistochemistry staining. NF-κB expression was assessed using western blotting. When NF-κB was inhibited by BAY 11–7821, expressions of NF-κB, E-cadherin and Vimentin were measured. Results The protein expression of E-cadherin in bronchial epithelial cells was lowest in CSE + IL-17A group, followed by CSE group. In contrast, the protein expression of Vimentin was highest in CSE + IL-17A group, followed by CSE group. Similarly, IL-17R and NF-κB expressions were highest in CSE + IL-17A group, followed by CSE group and IL-17A group. NF-κB inhibitor could inhibit the expressions of E-cadherin and Vimentin. Conclusions Cigarette and IL-17A could synergistically induce EMT in bronchial epithelial cells through activating IL17R/NF-κB signaling. Our findings contribute to a better understanding in airway EMT and pathogenesis of respiratory diseases, which are involved IL-17A and cigarette smoking. Those will provide novel avenues in the immunotherapy of lung diseases.

Emodin (EMO) possesses extensive pharmacological activities, which has been proven to exert the protective impact in diverse nervous system diseases. Nonetheless, whether EMO emerges a neuro-protective activity in hypoxic-evoked ischemic brain injury is still further probed. The intention of the research is to disclose whether EMO emerges neuro-protective activity in hypoxic-evoked ischemic brain injury. PC-12 received hypoxia administration, and then cell viability, apoptosis and autophagy were estimated. After EMO disposition, the above-involved cellular processes were evaluated again. MiR-25 functions in EMO-affected cells were also estimated. The interrelation between miR-25 and neurofilament light-chain polypeptide gene (NEFL) and the conceivable roles of NEFL in hypoxia-disposed cells were investigated. The latent mechanism was uncovered by mTOR and Notch pathways determination. Hypoxia triumphantly triggered apoptosis and autophagy, but EMO repressed these functions in PC-12 cells. Increased miR-25 was induced by EMO, and inhibited miR-25 abated the impacts of EMO on hypoxia-disposed PC-12 cells. NEFL as a neoteric target gene of miR-25 was predicated, and overexpressed NEFL annulled the functions of EMO in hypoxia-injured cells. EMO activated mTOR and Notch pathways through repressing NEFL. The investigations corroborated that EMO weakened hypoxia-triggered injury via elevating miR-25 by targeting NEFL in PC-12 cells.

Our study examines Facebook posts containing nine prominent COVID-19 vaccine misinformation topics that circulated on the platform between March 1, 2020, and March 1, 2021. We first identify misinformation spreaders and fact checkers, further dividing the latter group into those who repeat misinformation to debunk the false claim and those who share correct information without repeating the misinformation. Our analysis shows that, on Facebook, there are almost as many fact checkers as misinformation spreaders. In particular, fact checkers’ posts that repeat the original misinformation received significantly more comments than posts from misinformation spreaders. However, we found that misinformation spreaders were far more likely to take on central positions in the misinformation URL co-sharing network than fact checkers. This demonstrates the remarkable ability of misinformation spreaders to coordinate communication strategies across topics.

A hybrid-clustering model is presented for the probabilistic characterization of ship traffic and anomaly detection. A hybrid clustering model was proposed to increase the efficiency of trajectory clustering in the port area and analyze the maritime traffic patterns in port. The model identified dissimilarities between trajectories based on characteristics, using K-Means and the density-based spatial clustering of applications with noise algorithm (DBSCAN). Firstly, the ship’s trajectory characteristics are constructed based on real ship trajectories considering static characteristics and dynamic characteristics of ship trajectories to calculate the characteristic dissimilarity between trajectories. Simultaneously, the spatial dissimilarity could be quantified using the Hausdorff algorithm. Then, the ship trajectory is clustered initially based on the departure and destination characteristics using K-Means algorithms to obtain various sub-trajectories. However, there are still different types of trajectories in each sub-trajectory. Thus, the DBSCAN algorithm is adopted to cluster the sub-trajectory based on the analysis of the different trajectory characteristics. Finally, the proposed model is applied to the characterization of the Zhanjiang Port, and the results show that the hybrid-clustering method can effectively cluster ship trajectory and present probabilistic characterization of ship traffic and anomaly detection. This lays a solid theoretical foundation for the supervision and risk control of intelligent ships.

This paper focuses on multi-target parameter estimation of multiple-input multiple-output (MIMO) radar with widely separated antennas on moving platforms. Aiming at the superimposed signals caused by multi-targets, the well-known expectation maximization (EM) is used in this paper. Target’s radar cross-section (RCS) spatial variations, different path losses and spatially-non-white noise appear because of the widely separated antennas. These variables are collectively referred to as signal-to-noise ratio (SNR) fluctuations. To estimate the echo delay/Doppler shift and SNR, the Q function of EM algorithm is extended. In addition, to reduce the computational complexity of EM algorithm, the gradient descent is used in M-step of EM algorithm. The modified EM algorithm is called generalized adaptive EM (GAEM) algorithm. Then, a weighted iterative least squares (WILS) algorithm is used to jointly estimate the target positions and velocities based on the results of GAEM algorithm. This paper also derives the Cramér-Rao bound (CRB) in such a non-ideal environment. Finally, extensive numerical simulations are carried out to validate the effectiveness of the proposed algorithm.

In this study, powdered activated carbon (PAC) was added to replace the silica in a cementitious microfiltration membrane (CM) to solve the problems of the low mechanical strength and short lifetime of CMs. The carbon-cementitious microfiltration membrane (CCM) was fabricated by the dry pressing method and cured at room temperature. The bending strength of CCM was 12.69 MPa, which was about three times more than that of CM. The average pore size was 0.129 μm, and was reduced by about 80% compared to that of CM. The addition of PAC did not reduce the degradation efficiency of membrane catalytic ozonation. Because of the strong alkaline buffering ability of CCM, the CCM–ozone coupling process could eliminate the effect of the pH value of the solution. The strong alkaline environment inside the membrane pores effectively accelerated the ozone decomposition and produced oxidizing radicals, which accelerated the reaction rate and improved the utilization rate of ozone. The CCM–catalytic ozonation reaction of organic compounds occurred within the pores and membrane surface, resulting in the pH of the solution belonging to the neutral range. The addition of PAC accelerated the mass transfer and made the pollutants and oxidant react in the membrane pores and on the membrane surface. The reuse experiments of the CCM–ozone coupling process for removing nitrobenzene demonstrated that CCM has good catalytic activity and reuse stability. It broadens the application scope of CCM in the field of drinking water and provides theoretical support for the practical application of CCM.

In this study, a low-cost cementitious microfiltration membrane (CM) with a catalytic ozone oxidation function for the removal of organic pollutants was fabricated by using cementitious and C-10 μm silica powders at a certain silica–cementitious particle ratio (s/c). The effect of the s/c on the pore size distribution and mechanical strength of the membrane was investigated. The membrane pore size showed a bimodal distribution, and the higher the s/c, the closer the second peak was to the accumulated average particle size of silica. The increase in the s/c led to a decrease in the bending strength of the membrane. The cross-sectional morphology by SEM and crystal structure by XRD of CMs confirmed that a calcium silicate hydrate gel was generated around the silica powder to improve the mechanical strength of the CM. Considering the bending strength and pore size distribution of CMs, s/c = 0.5 was selected as the optimal membrane fabrication condition. The FT-IR results characterizing the surface functional groups of CMs were rich in surface hydroxyl groups with the ability to catalyze ozone oxidation for organic pollutant removal. Six small molecule organic pollutants were selected as model compounds for the efficiency experiments via a CM–ozone coupling process to prove the catalytic property of the CM. The CM has an alkaline buffering effect and can stabilize the initial pH of the solution in the catalytic ozonation process. The reuse experiments of the CM–ozone coupling process demonstrated the broad spectrum of the CM catalytic performance and self-cleaning properties. The results of this study provide the basis and experimental support to expand the practical application of CMs.

For polarized remote sensors, the polarization images of ground objects acquired at different spatial scales will be different due to the spatial heterogeneity of the ground object targets and the limitation of imaging resolution. In this paper, the quantitative inversion problem of a typical polarized remote sensor at different spatial scales was studied. Firstly, the surface roughness of coatings was inversed based on the polarized bidirectional reflectance distribution function (pBRDF) model according to their polarization images at different distances. A linear-mixed pixel model was used to make a preliminary correction of the spatial scale effect. Secondly, the super-resolution image reconstruction of the polarization imager was realized based on the projection onto convex sets (POCS) method. Then, images with different resolutions at a fixed distance were obtained by utilizing this super-resolution image reconstruction method and the optimal spatial scale under the scene can be acquired by using information entropy as an evaluation indicator. Finally, the experimental results showed that the roughness inversion of coatings has the highest accuracy in the optimal spatial scale. It has been proved that our proposed method can provide a reliable way to reduce the spatial effect of the polarized remote sensor and to improve the inversion accuracy.

Influenza is active during the winter and spring in the city of Beijing, which has a typical temperate climate with four clear distinct seasons. The clinical and laboratory surveillance data for influenza have been used to construct critical indicators for influenza activities in the community, and previous studies have reported varying degrees of association between laboratory-confirmed influenza specimens and outpatient consultation rates of influenza-like illness in subtropical cities. However, few studies have reported on this issue for cities in temperate regions, especially in developing countries. Furthermore, the mechanism behind age-specific seasonal epidemics remains unresolved, although it has been widely discussed. We utilized a wavelet analysis method to monitor the coherence of weekly percentage of laboratory-confirmed influenza specimens with the weekly outpatient consultation rates of influenza-like illness in Beijing, China. We first examined the seasonal pattern of laboratory-confirmed cases of influenza A (subtyped into seasonal A(H1N1) and A(H3N2) and pandemic virus A(H1N1) pdm09) and influenza B separately within the period from 2008-2015; then, we detected the coherence of clinical and laboratory surveillance data in this district, specially examining weekly time series of age-specific epidemics of influenza-like illnesses in the whole study period for three age categories (age 0-5, 5-15 and 25-60). We found that influenza A and B were both active in winter but were not always seasonally synchronous in Beijing. Synchronization between age ranges was found in most epidemic peaks from 2008-2015. Our findings suggested that peaks of influenza-like illness in individuals aged 0-5 and 5-15 years consistently appeared ahead of those of adults, implying the possibility that schoolchildren may lead epidemic fluctuations.

OBJECTIVE: To investigate the feasibility of gadolinium (Gd) contrast-enhanced magnetic resonance lymphangiography (MRL) in breast cancer patients within a typical clinical setting, and to establish a Gd-MRL protocol and identify potential MRL biomarkers for differentiating metastatic from non-metastatic lymph nodes. MATERIALS AND METHODS: 32 patients with unilateral breast cancer were enrolled and divided into 4 groups of 8 patients. Groups I, II, and III received 1.0, 0.5, and 0.3 ml of intradermal contrast; group IV received two 0.5 ml doses of intradermal contrast. MRL images were acquired on a 3.0 T system and evaluated independently by two radiologists for the number and size of enhancing lymph nodes, lymph node contrast uptake kinetics, lymph vessel size, and contrast enhancement patterns within lymph nodes. RESULTS: Group III patients had a statistically significant decrease in the total number of enhancing axillary lymph nodes and lymphatic vessels compared to all other groups. While group IV patients had a statistically significant faster time to reach the maximum peak enhancement over group I and II (by 3 minutes), there was no other statistically significant difference between imaging results between groups I, II, and IV. 27 out of 128 lymphatic vessels (21%) showed dilatation, and all patients with dilated lymphatic vessels were pathologically proven to have metastases. Using the pattern of enhancement defects as the sole criterion for identifying metastatic lymph nodes during Gd-MRL interpretation, and using histopathology as the gold standard, the sensitivity and specificity were estimated to be 86% and 95%, respectively. CONCLUSION: Gd-MRL can adequately depict the lymphatic system, can define sentinel lymph nodes, and has the potential to differentiate between metastatic and non-metastatic lymph nodes in breast cancer patients.