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•What is the primary question addressed by this study?The present study sought to understand whether the presence of the APOE-ε4 allele results in differential cognitive outcomes following the interacting effects of decreasing in PM2.5levels over time and aging.•What is the main finding of this study?The results showed high levels of PM2.5across all visits were significantly associated with worsening of scores on the overall MMSE.Participants demonstrated cognitive decline with an average MMSE score decline of 1.11 per year. Carriers of ε4/ε4 alleles in APOEhad significantly 3.68-fold risks of MMSE decline.•What is the meaning of the finding?Although the annual PM2.5levels decreased over time, the results still indicated that long-term exposure to PM2.5, was associated with an increased risk of MMSE decline.

A new homogenization kinetics prediction model for wrought superalloys based on the concept of diffusion distance was proposed. The micro-segregation and homogenization kinetics of Ni-based wrought superalloy, GH4141, were systematically studied by using the quantitative electron prob X-ray micro-analyzer (EPMA) analyses. There is a discrepancy between the predicted homogenization kinetics by the residual segregation index model and the experimental measurement. Both the experiments and theoretical analyses reveal that the homogenization kinetics can be reasonably predicted by the diffusion distance model under 1D-diffusion condition, with considering the diffusion-direction factor that is usually ignored. The new model provides a new option for predicting the homogenization kinetics with only necessarily knowing the original dendrite arm spacing and diffusion coefficient.

Esculetin (ESC) is a coumarin-derived phytochemical prevalent in traditional Chinese medicine that exhibits anti-acute ischemic stroke activities. Our previous studies demonstrate that CKLF1 is a potential anti-stroke target for coumarin-derived compound. In this study we investigated whether CKLF1 was involved in the neuroprotective effects of ESC against photothrombotic stroke in mice. The mice were treated with ESC (20, 40 or 80 mg·kg−1·d−1, i.g.) for two weeks. The therapeutic effect of ESC was assessed using MRI, neurological function evaluation, and a range of behavioral tests on D1, 3, 7 and 14 of ESC administration. We showed that oral administration of ESC dose-dependently reduced the cerebral infarction volume within one week after stroke, improved behavioral performance, and alleviated neuropathological damage within two weeks. Functional MRI revealed that ESC significantly enhanced the abnormal low-frequency fluctuation (ALFF) value of the motor cortex and promoted functional connectivity between the supplementary motor area (SMA) and multiple brain regions. We demonstrated that ESC significantly reduced the protein levels of CKLF1 and CCR5, as well as the CKLF1/CCR5 protein complex in the peri-infarcted area. We showed that ESC (0.1–10 μM) dose-dependently blocked CKLF1-induced chemotactic movement of neutrophils in the Transwell assay, reducing the interaction of CKLF1/CCR5 on the surface of neutrophils, thereby reducing neutrophil infiltration, and decreasing the expression of ICAM-1, VCAM-1 and MMP-9 in the peri-infarct tissue. Knockout of CKLF1 reduced brain infarction volume and motor dysfunction after stroke but also negated the anti-stroke efficacy and neutrophil infiltration of ESC. These results suggest that the efficacy of ESC in promoting post-stroke neural repair depends on its inhibition on CKLF1-mediated neutrophil infiltration, which offering novel perspectives for elucidating the therapeutic properties of coumarins.

Herein, by modulating 2DEG concentration ( ${n} _{\mathbf {s}}$ ), a superior GaN RF HEMT with a high-Al-content AlGaN barrier is reported for high power-density ( ${P} _{\text {out}}$ ) X-band applications. Thanks to a high ${n} _{\text {s}}$ of ${1}.{3}\times {10} ^{{13}}$ cm $^{-{2}}$ enabled by the Al $_{{0}.{32}}$ Ga $_{{0}.{68}}$ N barrier, as well as the regrown n+ -GaN ohmic contacts, the device exhibits an output drain current ( ${I} _{\text {D}}$ ) of 1.6 A/mm, an on-resistance ( ${R} _{\text {ON}}$ ) of $1.10\Omega ~\cdot $ mm, and maintain a breakdown electric field ( ${E} _{\text {BC}}$ ) of ~0.8 MV/cm. As a result, at 10 GHz, ${P} _{\text {out}}$ of 10.4 W/mm and power-added efficiency (PAE) of 63.2% are obtained at a moderate drain bias ( ${V} _{\text {D}}$ ) of 28 V. Notably, the results of ${I} _{\mathbf {D}}$ – ${E} _{\text {BC}}$ , ${P} _{\text {out}}$ – ${V} _{\text {D}}$ , and the figure-of-merit ${P} _{\text {out}}$ / ${V} _{D}$ of our device marks one of the best records among X-band GaN HEMTs, showing strong competitiveness of high-Al-content AlGaN/GaN HEMTs for high- ${P} _{\text {out}}$ RF applications.

The tellurite toxicity in Haemophilus influenzaeand H. parainfluenzaeremains unclear. To understand the potential of tellurite as a therapeutic option for these bacteria, we investigated the antimicrobial efficacy of AS101, a tellurium compound, against H. influenzaeand H. parainfluenzaeand the molecular basis of their differences in AS101 susceptibility. Through broth microdilution, we examined the minimum inhibitory concentration (MIC) of AS101 in 51 H. influenzaeand 28 H. parainfluenzaeisolates. Whole-genome sequencing was performed on the H. influenzaeisolates to identify genetic variations associated with AS101 susceptibility. The MICs of AS101 were ≦ 4, 16–32, and ≧ 64 μg/mL in 9 (17.6%), 12 (23.5%), and 30 (58.8%) H. influenzaeisolates, respectively, whereas ≦ 0.5 μg/mL in all H. parainfluenzaeisolates, including multidrug-resistant isolates. Time-killing kinetic assay and scanning electron microscopy revealed the in vitro bactericidal activity of AS101 against H. parainfluenzae. Forty variations in nine tellurite resistance-related genes were associated with AS101 susceptibility. Logistic regression, receiver operator characteristic curve analysis, Venn diagram, and protein sequence alignment indicated that Val195Ile substitution in TerC, Ser93Gly in Gor (glutathione reductase), Pro44Ala/Ala50Pro in NapB (nitrate reductase), Val307Leu in TehA (tellurite resistance protein), Cys105Arg in CysK (cysteine synthase), and Thr364Ser in Csd (Cysteine desulfurase) were strongly associated with reduced AS101 susceptibility, whereas Ser155Pro in TehA with increased AS101 susceptibility. In conclusions, the antimicrobial efficacy of AS101 is high against H. parainfluenzaebut low against H. influenzae. Genetic variations and corresponding protein changes relevant to AS101 non-susceptibility in H. influenzaewere identified.

Development of the cerebellum requires precise regulation of granule neuron progenitor (GNP) proliferation. Although it is known that primary cilia are necessary to support GNP proliferation, the exact molecular mechanism governing primary cilia dynamics within GNPs remains elusive. Here, we establish the pivotal roles for the centrosomal kinase TTBK2 (Tau tubulin kinase-2) and the E3 ubiquitin ligase HUWE1 in GNP proliferation. We show that TTBK2 is highly expressed in proliferating GNPs under Sonic Hedgehog (SHH) signaling, coinciding with active GNP proliferation and the presence of primary cilia. TTBK2 stabilizes primary cilia by inhibiting their disassembly, thereby promoting GNP proliferation in response to SHH. Mechanistically, we identify HUWE1 as a novel centrosomal E3 ligase that facilitates primary cilia disassembly by targeting TTBK2 degradation. Disassembly of primary cilia serves as a trigger for GNP differentiation, allowing their migration from the external granule layer (EGL) of the cerebellum to the internal granule layer (IGL) for subsequent maturation. Moreover, we have established a link between TTBK2 and SHH-type medulloblastoma (SHH-MB), a tumor characterized by uncontrolled GNP proliferation. TTBK2 depletion inhibits SHH-MB proliferation, indicating that TTBK2 may be a potential therapeutic target for this cancer type. In summary, our findings reveal the mechanism governing cerebellar development and highlight a potential anti-cancer strategy for SHH-MB.

In power conversion systems, the power devices often need to block high voltage levels during the OFF-state. The impact of such voltage stress can cause instability for the device. This article presents the investigation of the pulsed ${I}$ – ${V}$ (PIV) OFF-state drain stress test for the etch-free hydrogen plasma-treated p-GaN gate HEMT (H-treated devices). To quantitatively demonstrate the effect of the hydrogen plasma treatment process, the device with conventional p-GaN etching at the access region (etched devices) is monolithically fabricated. Remarkably, the hydrogen treatment could eliminate surface damage from the conventional etching process and provide passivation at the access region. The direct comparison of devices’ threshold voltage ( ${V} _{\text {TH}}$ ) shift and dynamic ON-resistance ( ${R} _{\text {on}}$ ) is obtained. Under a 200-V OFF-state drain stress, the H-treated device has a low ${V} _{\text {TH}}$ shift of 0.18 V, and the dynamic ${R} _{\text {on}}$ could also be efficiently suppressed by 24%. Meanwhile, the H-treated device has only a marginal 5% current reduction compared with 48% for the etched device at 200-V stress. An exploration of the origin of the superior device performances is carried out with the TCAD simulation, activation energy derivation, and capacitance measurement. For the H-treated device, the surface state improvement at the region and the reduction of the peak electric field at the gate edge become major reasons for the improved performance.

The Pencil Beam Scanning (PBS) technique in modern particle therapy offers a highly conformal dose distribution but poses challenges due to the interplay effect, an interaction between respiration-induced organ movement and PBS. This study evaluates the effectiveness of different volumetric rescanning strategies in mitigating this effect in liver cancer proton therapy. We used a Geant4-based Monte Carlo simulation toolkit, ‘TOPAS,’ and an image registration toolbox, ‘Elastix,’ to calculate 4D dose distributions from 5 patients’ four-dimensional computed tomography (4DCT). We analyzed the homogeneity index (HI) value of the Clinical Tumor Volume (CTV) at different rescan numbers and treatment times. Our results indicate that dose homogeneity stabilizes at a low point after a week of treatment, implying that both rescanning and fractionation treatments help mitigate the interplay effect. Notably, an increase in the number of rescans doesn’t significantly reduce the mean dose to normal tissue but effectively prevents high localized doses to tissue adjacent to the CTV. Rescanning techniques, based on statistical averaging, require no extra equipment or patient cooperation, making them widely accessible. However, the number of rescans, tumor location, diaphragm movement, and treatment fractionation significantly influence their effectiveness. Therefore, deciding the number of rescans should involve considering the number of beams, treatment fraction size, and total delivery time to avoid unnecessary treatment extension without significant clinical benefits. The results showed that 2–3 rescans are more clinically suitable for liver cancer patients undergoing proton therapy.

Data-driven damage-detection schemes are usually unsupervised machine-learning models in practice, as these do not require any training. Vibration-based features are commonly used in these schemes but often require several other parameters to accurately correlate with damage, as they may not globally represent the model, making them less sensitive to damage. Modal data, such as frequency response functions (FRFs) and principal component analysis (PCA) reduced FRFs (PCA-FRFs), inherits the dynamic characteristics of the structure, and it changes when damage occurs, thus showing sensitivity to damage. However, noise from the environment or external sources such as wind, operating machines, or the in-service system itself, can reduce the modal data’s sensitivity to damage if not handled properly, which affects damage-detection accuracy. This study proposes a noise-robust operational modal-based structural damage-detection scheme that uses impact-synchronous modal analysis (ISMA) to generate clean, static-like FRFs for damage diagnosis. ISMA allows modal data collection without requiring shutdown conditions, and its denoising feature aids in generating clean, static-like FRFs for damage diagnosis. Our results showed that the FRFs obtained through ISMA under noise conditions have frequency response assurance criterion (FRAC) and cross signature assurance criterion (CSAC) scores greater than 0.9 when compared with FRFs obtained through experimental modal analysis (EMA) under static conditions; this validates the denoising feature of ISMA. When the denoised FRFs are reduced to PCA-FRFs and used in an unsupervised learning-based damage-detection scheme, zero false alarms occur.

Natural products have long been a crucial source of, or provided inspiration for new agrochemical discovery. Naturally occurring 18β-glycyrrhetinic acid shows broad-spectrum bioactivities and is a potential skeleton for novel drug discovery. To extend the utility of 18β-glycyrrhetinic acid for agricultural uses, a series of novel 18β-glycyrrhetinic acid amide derivatives were prepared and evaluated for their antibacterial potency. Notably, compound 5k showed good antibacterial activity in vitroagainst Xanthomonas oryzaepv. oryzae(Xoo, EC50=3.64 mg L–1), and excellent protective activity (54.68%) against Xoo in vivo. Compound 5k induced excessive production and accumulation of reactive oxygen species in the tested pathogens, resulting in damaging the bacterial cell envelope. More interestingly, compound 5k could increase the activities of plant defense enzymes including catalase, superoxide dismutase, peroxidase, and phenylalanine ammonia lyase. Taken together, these enjoyable results suggested that designed compounds derived from 18β-glycyrrhetinic acid showed potential for controlling intractable plant bacterial diseases by disturbing the balance of the phytopathogen’s redox system and activating the plant defense system.

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ABSTRACTKetamine is an anesthetic, which when used wrongly would affect judgment and behavior, increasing risks to individual such as unwanted or risky sexual behavior. This study reports the development of an admittance- and capacitance-spectroscopy-based sensor to detect ketamine in solution, such as whiskey, a popular alcoholic drink. The result confirms the proposed method is capable of detecting the presence of ketamine in whiskey, in concentration as low as 6.25 ng/μL, by using admittance and capacitance measured at 6.75 MHz, as well as quantifying the measured admittance (sensitivity: 300 μΩ−1/Log (ng/μL); limit of detection (LOD): 0.16 ng/μL) or capacitance data (sensitivity: 2 nF/Log (ng/μL); LOD: 0.73 ng/μL) at 18 kHz and 7.69 MHz, respectively.

In the context of sustainable development, research regarding chirality has aroused enormous attention. Concurrently, chiral self-assembly is one of the most important subjects in supramolecular research, which can broaden the applications of chiral materials. This study focuses on the morphology control of amphiphilic rod-coil molecules composed of the rigid hexaphenyl unit and flexible oligoethylene and butoxy groups containing lateral methyl groups, carried out using an enantioseparation application. The methyl side chain being located on different blocks influences the driving force through steric hindrance, which determines the direction and degree of tilted packing during the π–π stacking of the self-assembly process. Interestingly, the amphiphilic rod-coil molecules aggregated into long helical nano-fibers, which further hierarchically aggregated into nano-sheets or nano-tubes upon increasing the concentration of the THF/H2O solution. In particular, the hierarchical-chiral assembly effectively amplified the chirality and was validated by the strong Cotton signals; playing a vital role in the enantioselective nucleophilic substitution reaction. These results provide new insights into the applications of chiral self-assemblies and soft chiral materials.

Recommendation systems have become more important since the widespread use of the Internet. The large amount of information means that it is difficult for users to discover what they really need. However, users’ preferences can change over time because of the age and the impact of social networks. Recommendation systems must capture users’ preferences and recommend suitable items, which is a difficult challenge. This study proposes a novel recommendation system that adapts to the changing preferences of users. By learning and adapting to users’ changing preferences better recommendations are provided. This study uses context factors as additional information to model users’ preferences more accurately. For the proposed recommendation system, the context is based on users’ most recent interaction items. This study proposes two novel attention mechanisms for the recommendation system. The contextual item attention module captures contextual information, changing pattern in users’ preference and the importance of items. The multi-head attention module extends the diversity of users’ preferences and adapts to changing preferences. The recommendation performance is improved using additional item's temporal information to model the contextual item's representation. Experiments compare the proposed algorithm with several state-of-the-art recommendation methods using three real-world datasets. The experimental results demonstrate that the proposed context-aware recommendation model outperforms traditional methods and demonstrate the effectiveness with which contextual information is captured by the attention mechanism.

Osmotic stress significantly hampers plant growth and crop yields, emphasizing the need for a thorough comprehension of the underlying molecular responses. Previous research has demonstrated that osmotic stress rapidly induces calcium influx and signaling, along with the activation of a specific subset of protein kinases, notably the Raf-like protein (RAF)-sucrose nonfermenting-1–related protein kinase 2 (SnRK2) kinase cascades within minutes. However, the intricate interplay between calcium signaling and the activation of RAF-SnRK2 kinase cascades remains elusive. Here, in this study, we discovered that Raf-like protein (RAF) kinases undergo hyperphosphorylation in response to osmotic shocks. Intriguingly, treatment with the calcium chelator EGTA robustly activates RAF-SnRK2 cascades, mirroring the effects of osmotic treatment. Utilizing high-throughput data-independent acquisition–based phosphoproteomics, we unveiled the global impact of EGTA on protein phosphorylation. Beyond the activation of RAFs and SnRK2s, EGTA treatment also activates mitogen-activated protein kinase cascades, Calcium-dependent protein kinases, and receptor-like protein kinases, etc. Through overlapping assays, we identified potential roles of mitogen-activated protein kinase kinase kinase kinases and receptor-like protein kinases in the osmotic stress–induced activation of RAF-SnRK2 cascades. Our findings illuminate the regulation of phosphorylation and cellular events by Ca2+signaling, offering insights into the (exocellular) Ca2+deprivation during early hyperosmolality sensing and signaling.

SARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals1,2. The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic. Here we show that without vaccination, infection with Omicron induces a limited humoral immune response in mice and humans. Sera from mice overexpressing the human ACE2 receptor and infected with Omicron neutralize only Omicron, but not other variants of concern, whereas broader cross-variant neutralization was observed after WA1 and Delta infections. Unlike WA1 and Delta, Omicron replicates to low levels in the lungs and brains of infected animals, leading to mild disease with reduced expression of pro-inflammatory cytokines and diminished activation of lung-resident T cells. Sera from individuals who were unvaccinated and infected with Omicron show the same limited neutralization of only Omicron itself. By contrast, Omicron breakthrough infections induce overall higher neutralization titres against all variants of concern. Our results demonstrate that Omicron infection enhances pre-existing immunity elicited by vaccines but, on its own, may not confer broad protection against non-Omicron variants in unvaccinated individuals.

Plant viral diseases cause the loss of millions of dollars to agriculture around the world annually. Therefore, the development of highly efficient, ultra-low-dosage agrochemicals is desirable for protecting the health of crops and ensuring food security. Herein, a series of 1,3,4-oxadiazole derivatives bearing an isopropanol amine moiety was prepared, and the inhibitory activity against tobacco mosaic virus (TMV) was assessed. Notably, compound A14exhibited excellent anti-TMV protective activity with an EC50value of 137.7 mg L–1, which was superior to that of ribavirin (590.0 mg L–1) and ningnanmycin (248.2 mg L–1). Moreover, the anti-TMV activity of some compounds could be further enhanced (by up to 5–30%) through supplementation with 0.1% auxiliaries. Biochemical assays suggested that compound A14could suppress the biosynthesis of TMV and induce the plant’s defense response. Given these merits, designed compounds had outstanding bioactivities and unusual action mechanisms and were promising candidates for controlling plant viral diseases.

A safe, biocompatible, and stimuli-responsive cucurbit[7]uril-mediated supramolecular bactericidal nanoparticle was fabricated by encapsulating a highly bioactive carbazole-decorated imidazolium salt (A1, EC50= 0.647 μg/mL against phytopathogen Xanthomonas oryzaepv oryzae) into the host cucurbit[7]uril (CB[7]), thereby leading to self-assembled topographies from microsheets (A1) to nanospheroidal architectures (A1@CB[7]). The assembly behaviors were elucidated by acquired single-crystal structures, 1H NMR, ITC, and X-ray powder diffraction experiments. Complex A1@CB[7] displayed lower phytotoxicity and could efficiently switch on its potent antibacterial ability via introducing a simple competitor 1-adamantanamine hydrochloride (AD). In vivoantibacterial trials against rice bacterial blight revealed that A1@CB[7] could relieve the disease symptoms after being triggered by AD and provide a workable control efficiency of 42.6% at 100 μg/mL, which was superior to bismerthiazol (33.4%). These materials can provide a viable platform for fabricating diverse stimuli-responsive supramolecular bactericides for managing bacterial infections with improved safety.

Bacterial biofilms are the root cause of persistent and chronic phytopathogenic bacterial infections. Therefore, developing novel agrochemicals that target the biofilm of phytopathogenic bacteria has been regarded as an innovative tactic to suppress their invasive infection or decrease bacterial drug resistance. In this study, a series of natural pterostilbene (PTE) derivatives were designed, and their antibacterial potency and antibiofilm ability were assessed. Notably, compound C1displayed excellent antibacterial potency in vitro, affording an EC50value of 0.88 μg mL–1against Xoo(Xanthomonas oryzaepv. oryzae). C1could significantly reduce biofilm formation and extracellular polysaccharides (EPS). Furthermore, C1also possessed remarkable inhibitory activity against bacterial extracellular enzymes, pathogenicity, and other virulence factors. Subsequently, pathogenicity experiments were further conducted to verify the above primary outcomes. More importantly, C1with pesticide additives displayed excellent control efficiency. Given these promising profiles, these pterostilbene derivatives can serve as novel antibiofilm agents to suppress plant pathogenic bacteria.

ABSTRACTBackgroundGO-Y078, a new synthetic analogue of curcumin (CUR), has higher oral bioavailability and anticancer activity than CUR, but the oncostatic effect of GO-Y078 on oral squamous cell carcinoma (OSCC) is largely unknown.Research design and methodsIn the present study, we examined the oncostatic properties and possible mechanisms of GO-Y078 on human SCC-9 and HSC-3 OSCC cells.ResultsOur results indicated that GO-Y078 showed a cytostatic effect against OSCC cells, and this antiproliferative phenomenon stemmed from a mechanism involving multiple levels of cooperation, including cell-cycle G2/M arrest and apoptosis induction. Mechanistically, GO-Y078 treatment induced caspase-mediated apoptosis via upregulating two apoptosis-modulating proteins, SMAC/DIABLO and heme oxygenase (HO)-1. GO-Y078 transcriptionally induced upregulation of the HO-1 gene by increasing the AP-1 DNA-binding activity, which was initiated by activation of the p38 /JNK1/2 pathways. In the clinic, patients with head and neck cancers expressed lower HO-1 and SMAC/DIABLO levels in primary cancer tissues compared to normal tissues. Clinical datasets also revealed that patients with head and neck cancers expressing high HO-1 had afavorable prognosis.ConclusionsOur results provide new insights into the role of GO-Y078-induced molecular regulation in suppressing OSCC growth and suggest that GO-Y078 has potential therapeutic applications for OSCC.

The Gamma-ray Transient Monitor (GTM) is an all-sky monitor onboard the Distant Retrograde Orbit-A (DRO-A) satellite with the scientific objective of detecting gamma-ray transients ranging from 20 keV to 1 MeV. The GTM was equipped with five Gamma-ray Transient Probe (GTP) detector modules utilizing a NaI(Tl) scintillator coupled with a SiPM array. To reduce the SiPM noise, GTP uses a dedicated dual-channel coincident readout design. In this work, we first studied the impact of different coincidence times on the detection efficiency and ultimately selected a 0.5 µs time coincidence window for offline data processing. To test the performance of the GTPs and validate the Monte-Carlo-simulated energy response, we conducted comprehensive ground calibration tests using the Hard X-ray Calibration Facility (HXCF) and radioactive sources, including the energy response, detection efficiency, spatial response, bias-voltage response, and temperature dependence. We extensively present the ground calibration results and validate the design and mass model of the GTP detector, thus providing the foundation for in-flight observations and scientific data analysis.

The agriculture, animal husbandry, and healthcare workers, due to frequent exposure to prophylactic antibiotic use in their work environments, face an increased risk of workers developing antimicrobial resistance (AMR), leading to biological hazards and occupational infection risks.This study collecting data from the Taiwan Labor Insurance and National Health Insurance databases. The investigation period from 2004 to 2020, and the study sample consisted of high-risk exposed groups, including those in agriculture, animal husbandry, and healthcare workers. The study aimed to compare antibiotic resistance, tuberculosis prevalence, and the risk ratio for hospital-acquired infections associated with antimicrobial resistance (AMR).Research findings showed higher AMR infection rates in agriculture and animal husbandry (8.33 per 100,000 person-years) compared to healthcare (4.71 per 100,000 person-years). Tuberculosis rates were notably higher in agriculture and animal husbandry (31.74 per 100,000 person-years) than in healthcare (18.95 per 100,000 person-years). The AMR infection risk ratio between the two sectors was 1.77, while for tuberculosis, it was 1.67. Among individuals aged over 65 in agriculture and animal husbandry, the risk of tuberculosis was significantly elevated compared to healthcare (RR = 2.00).Global AMR research highlights high-risk jobs in healthcare, veterinary medicine, slaughterhouses, farming, and aquaculture. Aquaculture presents unique risks, such as marine vibrio infections due to sunburn and fish stings, necessitating the need for protection and education. Raising awareness in these sectors is crucial for controlling the spread of pathogens. Integrating AMR monitoring into disaster planning for these roles is vital. Physicians should expand data collection (Travel, Occupation, Contact, Cluster) during checkups to facilitate early AMR detection and data gathering.

The global outbreak of the COVID-19 pandemic has expedited the adoption of remote work practices by businesses worldwide. In order to understand the experiences of remote workers in Taiwan during the COVID-19 pandemic, this study aims to investigate issues related to labor time management and the various physical, mental, and socio-psychological factors affecting remote workers in Taiwan.In this study, a questionnaire survey was employed to compare the experiences of remote workers in office-based and home-based settings during the COVID-19 pandemic in Taiwan in May 2021. The research focused on examining differences in socio-psychological factors related to workstation ergonomics, work and rest periods, gender-related work-family conflicts, and fatigue.The study collected 502 valid questionnaires from 11 businesses. Remote work increased from 24.7% pre-pandemic to 48.7% (P<0.001), with ≥4-hour weekly online conferencing. Of those surveyed, 56.6% used laptops, and 21.7% reported experiencing constant eye fatigue. Home-based remote work showed that females experienced slight psychological distress. Individuals aged 40-49 and 50-59, caregivers, cohabitants, and married individuals reported higher work-family conflict scores. Caregivers and married individuals also reported significantly higher levels of personal fatigue.During the COVID-19 pandemic, the global remote workers, including those in Taiwan, exhibited similar health challenges, such as increased eye fatigue, higher fatigue and work-family conflict among caregivers and married individuals, and greater psychological burden on females. Recommendations include improving remote work conditions, providing ergonomic equipment, eye health education, and developing policies for remote work well-being. This holistic approach addresses both physical and psychological needs, fostering a supportive and productive remote work environment amidst pandemic challenges.

Germline variant interpretation often depends on population-matched control cohorts. This is not feasible for population groups that are underrepresented in current population reference databases.

To unceasingly expand the molecular diversity of 1,3,4-oxadiazole-2-carbohydrazides, herein, small fragments (including −CH2–, −OCH2–, and −SCH2−) were incorporated into the target compounds to screen out the potential succinate dehydrogenase inhibitors (SDHIs). The bioassay results showed that the antifungal effects (expressed by EC50) against Sclerotinia sclerotiorum, Botryosphaeria dothidea, Fusarium oxysporum, and Colletotrichun higginsianumcould reach 1.29 (10a), 0.63 (8h), 1.50 (10i), and 2.09 (10i) μg/mL, respectively, which were slightly lower than those of carbendazim (EC50were 0.69, 0.13, 0.55, and 0.80 μg/mL, respectively). Especially, compound 10hwas extremely bioactive against Gibberella zeae(G. z.) with an EC50value of 0.45 μg/mL. This outcome was better than that of fluopyram (3.76 μg/mL) and was similar to prochloraz (0.47 μg/mL). In vivotrials against the corn scab (infected by G. z.) showed that compound 10hhad control activity of 86.8% at 200 μg/mL, which was better than that of boscalid (79.6%). Further investigations found that compound 10hcould inhibit the enzymatic activity of SDH in the G. z.strain with an IC50value of 3.67 μM, indicating that potential SDHIs might be developed. Additionally, the other biological activities of these molecules were screened simultaneously. The anti-oomycete activity toward Phytophthora infestansafforded a minimal EC50value of 3.22 μg/mL (10h); compound 4dcould strongly suppress the growth of bacterial strains Xanthomonas axonopodispv. citriand Xanthomonas oryzaepv. oryzaewith EC50values of 3.79 and 11.4 μg/mL, respectively; and compound 10adisplayed some insecticidal activity toward Plutella xylostella. Given their multipurpose features, these frameworks could be actively studied as potential pesticide leads.

Filamin C (FLN c) is a novel allergen in shellfish. In this study, FLN c from Scylla paramamosainwas divided into three regions for recombinant expression based on the number of domains and amino acids. Using dot blot and basophil activation tests, the allergic predominant region of FLN c was determined to be 336–531 amino acid positions (named FLN c-M). It was confirmed that by X-ray diffraction, the crystal structure of FLN c-M with immunoglobulin-like folding at a resolution of 1.7 Å was obtained. The monomer was a barrel structure composed of 16 β-strands and 2 α-helices. Three conformational epitopes were predicted, six linear epitopes were verified by serological test, and they were positioned on the crystal structure of FLN c-M. For the first time, the crystal structure of the allergic predominant region of FLN c was determined, and it provided an accurate template for the localization of IgE epitopes.