Synergizing physics and machine learning for advanced battery management.

Improving battery health and safety motivates the synergy of a powerful duo: physics and machine learning. Through seamless integration of these disciplines, the efficacy of mathematical battery models can be significantly enhanced. This paper delves into the challenges and potentials of managing battery health and safety, highlighting the transformative impact of integrating physics and machine learning to address those challenges. Based on our systematic review in this context, we outline several future directions and perspectives, offering a comprehensive exploration of efficient and reliable approaches. Our analysis emphasizes that the integration of physics and machine learning stands as a disruptive innovation in the development of emerging battery health and safety management technologies.

Proteomic and Phosphoproteomic Profiling of Matrix Stiffness-Induced Stemness-Dormancy State Transition in Breast Cancer Cells.

The dormancy of cancer stem cells is a major factor leading to drug resistance and a high rate of late recurrence and mortality in estrogen receptor-positive (ER+) breast cancer. Previously, we demonstrated that a stiffer matrix induces tumor cell dormancy and drug resistance, whereas a softened matrix promotes tumor cells to exhibit a stem cell state with high proliferation and migration. In this study, we present a comprehensive analysis of the proteome and phosphoproteome in response to gradient changes in matrix stiffness, elucidating the mechanisms behind cell dormancy-induced drug resistance. Overall, we found that antiapoptotic and membrane transport processes may be involved in the mechanical force-induced dormancy resistance of ER+ breast cancer cells. Our research provides new insights from a holistic proteomic and phosphoproteomic perspective, underscoring the significant role of mechanical forces stemming from the stiffness of the surrounding extracellular matrix as a critical regulatory factor in the tumor microenvironment.

Genome Sequencing of Three Pathogenic Fungi Provides Insights into the Evolution and Pathogenic Mechanisms of the Cobweb Disease on Cultivated Mushrooms.

Fungal diseases not only reduce the yield of edible mushrooms but also pose potential threats to the preservation and quality of harvested mushrooms. Cobweb disease, caused primarily by fungal pathogens from the Hypocreaceae family, is one of the most significant diseases affecting edible mushrooms. Deciphering the genomes of these pathogens will help unravel the molecular basis of their evolution and identify genes responsible for pathogenicity. Here, we present high-quality genome sequences of three cobweb disease fungi: Hypomyces aurantius Cb-Fv, Cladobotryum mycophilum CB-Ab, and Cladobotryum protrusum CB-Mi, isolated from Flammulina velutipes, Agaricus bisporus, and Morchella importuna, respectively. The assembled genomes of H. aurantius, C. mycophilum, and C. protrusum are 33.19 Mb, 39.83 Mb, and 38.10 Mb, respectively. This is the first report of the genome of H. aurantius. Phylogenetic analysis revealed that cobweb disease pathogens are closely related and diverged approximately 17.51 million years ago. CAZymes (mainly chitinases, glucan endo-1,3-beta-glucosidases, and secondary metabolite synthases), proteases, KP3 killer proteins, lipases, and hydrophobins were found to be conserved and strongly associated with pathogenicity, virulence, and adaptation in the three cobweb pathogens. This study provides insights into the genome structure, genome organization, and pathogenicity of these three cobweb disease fungi, which will be a valuable resource for comparative genomics studies of cobweb pathogens and will help control this disease, thereby enhancing mushroom quality.

Unraveling the Effect of Oxygen Vacancy on WO3 Surface for Efficient NO2 Detection at Low Temperature.

Oxygen vacancies (VO) in metal oxide semiconductors play an important role in improving gas-sensing performance of chemiresistive gas sensors. Nonetheless, there is still a lack of clear understanding of the inherent mechanism of the influence of oxygen vacancies on gas sensing due to generally focusing on the concentration of VO. Herein, oxygen vacancies were rationally modulated in WO3 nanoflower structures via an annealing process, resulting in a transformation of VO from neutral (VO0) to a doubly ionized (VO2+) state. Density functional theory (DFT) calculations indicate that VO2+ is significantly more efficient than VO0 for NO2 detection in competition with atmospheric O2. Benefiting from a high concentration of VO2+, the WO3-450 (WO3 annealed at 450 °C) sensor exhibits excellent sensing performance with an ultrahigh sensitivity (3674.1 to 5 ppm NO2), superior selectivity, and long-term stability (one month). Furthermore, the sensor with the wide range of concentration detection not only can detect NO2 gas with parts per million (ppm) but also can detect NO2 with parts per billion (ppb) level concentration, with a high sensibility reaching 2.8 to 25 ppb NO2 and over 100 to 100 ppb NO2. This study elucidates the oxygen vacancy mediated sensing mechanism toward NO2 and provides an effective strategy for the rational design of gas sensors with high sensing performance.

BSC2 modulates AmB resistance via the maintenance of intracellular sodium/potassium ion homeostasis in Saccharomyces cerevisiae.

Previous studies on BSC2 have shown that it enhances yeast cell resistance to AmB via antioxidation and induces multidrug resistance by contributing to biofilm formation. Herein, we found that BSC2 overexpression could reverse the sensitivity of pmp3Δ to AmB and help the tested strains restore the intracellular sodium/potassium balance under exposure to AmB. Meanwhile, overexpression of the chitin gene CHS2 could simulate BSC2 to reverse the sensitivity of pmp3Δ and nha1Δ to high salt or AmB. However, BSC2 overexpression in flo11Δ failed to induce AmB resistance, form biofilms, and affect cell wall biogenesis, while CHS2 overexpression compensated the resistance of flo11Δ to AmB. Additionally, BSC2 levels were positively correlated with maintaining cell membrane integrity under exposure to AmB, CAS, or a combination of both. BSC2 overexpression in nha1Δ exhibited a similar function of CHS2, which can compensate for the sensitivity of the mutant to high salt. Altogether, the results demonstrate for the first time that BSC2 may promote ion equilibrium by strengthening cell walls and inhibiting membrane damage in a FLO path-dependent manner, thus enhancing the resistance of yeast cells to AmB. This study also reveals the possible mechanism of antifungal drugs CAS and AmB combined to inhibit fungi.

More than three years' treatment response of recombinant human growth hormone in a patient with Coffin-Siris syndrome 7.

Not required for Clinical Vignette.

Mendelian randomization identifies causal associations between GWAS-associated bacteria and their metabolites and rheumatoid arthritis.

Background: Accumulating evidence suggests that an imbalance of gut microbiota is commonly observed in patients with rheumatoid arthritis (RA). However, it remains unclear whether gut microbiota dysbiosis is a cause or consequence of RA, and the mechanisms by which gut dysbiosis contributes to RA have not been fully understood. This study aimed to investigate the causal relationship between gut microbiota and metabolites with RA. Methods: A two-sample Mendelian randomization analysis was performed to estimate the causality of gut microbiota and metabolites on RA. A genome-wide association study (GWAS) of 211 gut microbiota and 217 metabolites was used as the exposure, whereas RA was treated as the outcome. Inverse variance weighted (IVW) was regarded as the primary approach for calculating causal estimates. MR Egger method, Weighted median method, Simple mode method, and weighted mode method were used for sensitive analysis. Metabolic pathway analysis was performed via the web-based Metaconflict 5.0. Additionally, an animal study was undertaken to evaluate the results inferred by Mendelian randomization. Result: This study indicated that six gut microbiota taxa (RuminococcaceaeUCG013, Erysipelotrichia, Erysipelotrichaceae, Erysipelotrichales, Clostridia, and Veillonellaceae) were estimated to exert a positive impact on RA. Conversely, seven gut microbiota taxa (Oxalobacter, Cyanobacteria, RuminococcaceaeUCG002, LachnospiraceaeUCG010, Christensenellaceae, Oxalobacteraceae, Anaerostipes) were estimated to exert a negative impact on RA. Three metabolites, namely indole-3-propionate (IPA), glycine and sphingomyelin (SM 16:1), were found to be linked to lower RA risk, while five metabolites (argininosuccinate, CE 20_4, TAG 58_8, PC 40_6, and LPC 20_4) were linked to higher RA risk. Additionally, four metabolic pathways were identified by metabolic pathway analysis. The collagen-induced arthritis (CIA) rats exhibited a higher relative abundance of Class_Clostridia and a lower abundance of Genus_Lachnospiraceae (p < 0.05) than the healthy controls. Conclusion: This study identified causal associations between specific gut microbiota, metabolites, and RA. These findings support the significant role of gut microbiota and metabolites in RA pathogenesis.

Inactivation of a Wheat Ribosomal Silencing Factor Gene TaRsfS Confers Resistance to Both Powdery Mildew and Stripe Rust.

Powdery mildew and stripe rust are major diseases on wheat worldwide that cause significant reductions in wheat production. The ribosomal silencing factor (RsfS) has been proven to regulate protein biosynthesis by inhibiting the translation process in bacterial response to stress. However, the role of RsfS in plant resistance to biotic stresses remains unclear. In this study, the RsfS homolog, TaRsfS was isolated from wheat. Overexpression of TaRsfS (TaRsfS-OE) reduces wheat resistance to powdery mildew and stripe rust and TaRsfS knockout (TaRsfS-KO) increases wheat resistance to both diseases without affecting key agronomic traits. The interaction protein of TaRsfS, 12-oxo-phytodienoic acid reductase 1 (TaOPR1), a key enzyme in the biosynthesis of jasmonic acid (JA), was screened and identified. Knocking-down and overexpression of TaOPR1 indicated that TaOPR1 positively regulates wheat resistance to powdery mildew and stripe rust. TaRsfS may regulate TaOPR1 at upstream, bind to the enzyme activity pocket of TaOPR1 and affect TaOPR1 enzyme activity, resulting in a reduced JA biosynthesis and wheat susceptible to powdery mildew and stripe rust. Collectively, TaRsfS is a susceptibility gene and negatively regulates wheat resistance to powdery mildew and stripe rust, and it has good potential for improving wheat resistance by genetic modifications.

General Defluoroalkylation of Trifluoromethylarenes with Both Electron-Donating and -Withdrawing Alkenes.

The incorporation of gem-difluoromethylene units into organic molecules remains a formidable challenge. Conventional methodologies for constructing aryldifluoromethyl derivatives relied on the use of high-functional fluorinating regents under harsh conditions. Herein, we report general and efficient photoredox catalytic systems for defluoroalkylation of readily available trifluoromethylarenes through selective C-F cleavage to deliver gem-difluoromethyl radicals which proceed through reductive addition to both electron-donating and withdrawing alkenes under transition-metal free conditions. Mechanistic studies reveal that thiol serves as both photocatalyst and HAT reagent under visible light irradiation. This synergistic photocatalysis and HAT catalysis protocol exhibits ample and salient features such as high chemo- and regioselectivity, broad substrate scope, amenable gram-scale synthesis and late-stage modification of bioactive molecules.

Impact of enniatins and beauvericin on lipid metabolism: Insights from a 3D HepaRG spheroid model.

Emerging mycotoxins enniatins (ENNs) and beauvericin (BEA) pose potential health risks to humans through dietary exposure. However, research into their mechanisms of toxicity is limited, with a lack of comprehensive toxicological data. This study investigates from a hepatic lipid metabolism perspective, establishing a more precise and reliable 3D HepaRG hepatocyte spheroid model as an alternative for toxicity assessment. Utilizing physiological indices, histopathological analyses, lipidomics, and molecular docking techniques, it comprehensively elucidates the effects of ENNs and BEA on hepatic lipid homeostasis and their molecular toxicological mechanisms. Our findings indicate that ENNs and BEA impact cellular viability and biochemical functions, significantly altering lipid metabolism pathways, particularly those involving glycerophospholipids and sphingolipids. Molecular docking has demonstrated strong binding affinity of ENNs and BEA with key enzymes in lipid metabolism such as Peroxisome Proliferator-Activated Receptor α (PPARα) and Cytosolic Phospholipase A2 (cPLA2), revealing the mechanistic basis for their hepatotoxic effects and potential to impair liver function and human health. These insights enhance our understanding of the potential hepatotoxicity of such fungal toxins and lay a foundation for the assessment of their health risks.

Efficacy of a Nutritional Cream Intervention to Treat Depression in Rescuers: A Randomized Controlled Trial.

Objective: To explore the effectiveness of a nutritional intervention in rescuers who screened positive for depression. Methods: A randomized controlled trial design was employed. From June to August, 2022, 4,460 rescuers were screened using the Self-Rating Depression Scale (SDS), and 1,615 positive cases were identified. Thirty-one volunteers were recruited and randomly divided into a nutritional intervention group and a control group. The intervention group received health education and nutritional intervention (a compound paste therapy primarily composed of red roses and Seville orange flowers), while the control group received psychological education. SDS scores were assessed before and after the intervention. Results: There was a statistically significant decline in SDS scores in the nutritional intervention group after the intervention ( P < 0.05). Furthermore, the SDS scores of the intervention group were significantly lower than those of the control group, both before and after the intervention ( P < 0.05). No severe adverse reactions were observed during safety evaluation. Conclusion: The nutritional intervention effectively reduced the depression scores in rescuers. Early nutritional intervention is recommended for rescuers who initially screen positive for depression.

Occurrence and health risk assessment of toxic metals and rare earth elements in microalgae: Insight into potential risk factors in new sustainable food resources.

Microalgae are a promising sustainable food source with high nutritional value and environmental benefits. This study investigated the presence of toxic metals and rare earth elements (REEs) in 68 microalgal-based food products and conducted a probabilistic risk assessment to evaluate potential health risks. The findings revealed high detection rates of REEs (80.96% to 100%) and heavy metals (83.82% to 100%), with REE concentrations ranging from 0.0055 to 0.5207 mg/kg. Heavy metals were detected at the following average concentrations: As (2.80 mg/kg) > Cr (1.27 mg/kg) > Pb (0.30 mg/kg) > Cd (0.20 mg/kg) > Hg (0.01 mg/kg). Carcinogenic risk analysis for Cd (3.004 × 10-3), Cr (1.484 × 10-3), and As (1.1283 × 10-2) indicated that 95th percentile values exceeded established safety thresholds (10-4). These findings highlight the critical need for stringent monitoring and the establishment of comprehensive regulatory frameworks for the safety of novel microalgae foods.

Dynamical analysis of a novel 2D Lyapunov exponent controllable memristive chaotic map.

The proposal of discrete memristors has made memristive chaotic maps based on them an important research topic. In this study, a new two-dimensional chaotic map without fixed points is constructed, and numerical simulation results display its rich dynamical behaviors. The analysis reveals the map's center inversion symmetry and Lyapunov exponent controller. The map exhibits complex dynamical behaviors, including memristor initial-boosting and single-parameter-offset boosting. Embedding the absolute value function within the memristor results in the emergence of localized boosting-free regions. Moreover, a class of multicavity transients is captured that greatly enhances the system's complexity. Ultimately, this map is implemented on the STM32 platform, demonstrating its practical applicability in potential practical application scenarios.

A clinically used anti-human papilloma virus agent (3-hydroxyphthalic anhydride-modified bovine ß-lactoglobulin) has a potential for topical application to prevent sexual transmission of monkeypox virus.

A global outbreak of monkeypox (mpox) caused by the mpox virus (MPXV) has posed a serious threat to public health worldwide, thus calling for the urgent development of antivirals and vaccines to curb its further spread. In this study, we screened 41 anhydride-modified proteins and found that 3-hydroxyphthalic anhydride-modified ß-lactoglobulin (3HP-ß-LG), a clinically used anti-HPV agent, was highly effective in inhibiting infection of vaccinia virus Tiantan strain (VACV-VTT) and MPXV. Mechanistic studies demonstrated that 3HP-ß-LG bound to the virus, not the host cell, by targeting the early stage of virus entry, possibly through the interaction between the amino acids with negatively charges in 3HP-ß-LG and the key amino acids with positive charges in the target region of A29L, a key surface protein of MPXV. A synergistic effect was observed when 3HP-ß-LG was combined with tecovirimat, a small-molecule antiviral drug approved by the United States Food and Drug Administration and the European Medicine Agency for the treatment of smallpox and mpox. Because of its clinically proven safety and stability, 3HP-ß-LG shows promise for further development as a prophylactic agent to prevent the sexual transmission of MPXV.

A self-reported symptom-based decision-making model helps to rule out outpatient cases at low risk for CRC before colonoscopy.

Objectives: Effective exclusion of low-risk symptomatic outpatient cases for colorectal cancer (CRC) remains diagnostic challenges. We aimed to develop a self-reported symptom-based decision-making model for application in outpatient scenarios. Methods: In total, 8233 symptomatic cases at risk for CRC, as judged by outpatient physicians, were involved in this study at seven medical centers. A decision-making model was constructed using 60 self-reported symptom parameters collected from the questionnaire. Further internal and external validation cohorts were built to evaluate the discriminatory power of the CRC model. The discriminatory power of the CRC model was assessed by the C-index and calibration plot. After that, the clinical utility and user experience of the CRC model were evaluated. Results: Nine symptom parameters were identified as valuable predictors used for modeling. Internal and external validation cohorts verified the adequate discriminatory power of the CRC model. In the clinical application step, all 17 physicians found the model easy to grasp, 99.9 % of the patients were satisfied with the survey form. Application of this model detected all CRC cases. The total consistency ratio of outpatient cases undergoing colonoscopy was 81.4 %. None of the low-risk patients defined by the CRC model had been diagnosed with CRC. Conclusion: This multicenter study developed and validated a simple and user-friendly decision-making model covering self-reported information. The CRC model has been demonstrated to perform well in terms of rapid outpatient decision-making scenarios and clinical utility, particularly because it can better rule out low-risk outpatient cases.

MiR319a-mediated salt stress response in poplar.

Maintenance of intracellular ion balance, especially Na+ and K+, plays an important role in plant responses to salt stress. Vessels in xylem are responsible for long-distance ion transport in vascular plants. Knowledge on the salt stress response in woody plants in limited. In this study, we identified miR319a as an important regulator in respond to salt stress in poplar. miR319a overexpression transgenic poplar showed a salt-tolerant phenotype, and cytological observation showed reduced cambium cell layers, wider xylem, increased number and lumen area of vessels and fibers, and thinner cell wall thickness in the transgenics. The miR319a-MIMIC plants, meanwhile, had opposite phenotypes, with narrower xylem, reduced number and lumen area of vessels and fibers cells, and increased wall thickness. In addition, overexpression of miR319a driven by the vessel-specific promoter significantly improved the salt tolerance compared with the fiber-specific promoter. The expression levels of PagHKT1;2 and PagSKOR1-b, which encoded high-affinity K+ and Na+ transporters for Na+ efflux and K+ influx, respectively, were positively correlated with the vessel number and lumen area. These results suggest that miR319 not only promotes ion transport rates by increasing vessel number and lumen area and reducing cell wall thickness, but also regulates the concentrations of Na+ and K+ in the xylem by up-regulating PagHKT1;2 and PagSKOR1-b. We demonstrate that miR319 may coordinate the response of poplar to salt stress through both mechanisms, enriching our understanding of the synergistic effects of the secondary xylem structure and long-distance ion transport balance in the salt tolerance of poplar.

Vitrification cryo-foil method for shoot tip cryopreservation and virus eradication in apple.

Establishment of a new method for improved shoot tip cryopreservation is crucial to facilitate the long-term preservation of plant germplasm as well as the use of cryotherapy for pathogen eradication. The present study reported a vitrification (V) cryo-foil method for shoot tip cryopreservation and virus eradication in apple. Shoot tip regrowth levels after cryopreservation were comparable among V cryo-foil (53 %), V cryo-plate (46 %) and conventional droplet vitrification (Dr-vi, 48 %). The V cryo-foil is more efficient to perform than Dr-vi as more shoot tips can be cryopreserved by one person. In the histological study applying an image-overlaying strategy, shoot tips cryopreserved by V cryo-foil showed a higher survival chance in the youngest leaf primordia than in the apical dome. When V cryo-foil was tested for virus eradication, fifty-five percent (55 %) of cryo-derived shoots were free of the apple stem pitting virus (ASPV), while none and less than 10 % were free of the apple stem grooving virus (ASGV) and the apple chlorotic leaf spot virus (ACLSV), respectively. Thus, these two viruses were efficiently preserved by V cryo-foil cryopreservation. Noticeably, although the shoot regrowth level was reduced to 27 %, a higher frequency (81 %) of ASPV eradication was achieved when a reduced duration of cryoprotectant exposure was applied in V cryo-foil, supporting the use of insufficient cryoprotection for improved virus eradication.

Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.

Substantial Underestimation of Fine-Mode Aerosol Loading from Wildfires and Its Radiative Effects in Current Satellite-Based Retrievals over the United States.

Wildfires generate abundant smoke primarily composed of fine-mode aerosols. However, accurately measuring the fine-mode aerosol optical depth (fAOD) is highly uncertain in most existing satellite-based aerosol products. Deep learning offers promise for inferring fAOD, but little has been done using multiangle satellite data. We developed an innovative angle-dependent deep-learning model (ADLM) that accounts for angular diversity in dual-angle observations. The model captures aerosol properties observed from dual angles in the contiguous United States and explores the potential of Greenhouse gases Observing Satellite-2's (GOSAT-2) measurements to retrieve fAOD at a 460 m spatial resolution. The ADLM demonstrates a strong performance through rigorous validation against ground-based data, revealing small biases. By comparison, the official fAOD product from the Moderate Resolution Imaging Spectroradiometer (MODIS), the Visible Infrared Imaging Radiometer Suite (VIIRS), and the Multiangle Imaging Spectroradiometer (MISR) during wildfire events is underestimated by more than 40% over western USA. This leads to significant differences in estimates of aerosol radiative forcing (ARF) from wildfires. The ADLM shows more than 20% stronger ARF than the MODIS, VIIRS, and MISR estimates, highlighting a greater impact of wildfire fAOD on Earth's energy balance.

Preparation and in vivo and ex vivo studies of sirolimus nano-in-situ gel ophthalmic formulation.

Sirolimus (SR) is a macrolide with antifungal and antitumor immunosuppressant properties, classified as a selective inhibitor of mammalian target of rapamycin (mTOR). In this study, an ionic in situ gel of SR (SR-SUS-ISG) was formulated using gellan gum, exhibiting stability regardless of temperature and pH variations, causing minimal irritation. Harnessing the physiological conditions of the eye, SR-SUS-ISG underwent gelation upon contact with ions, increasing drug viscosity and prolonging retention on the ocular surface. Concurrently, SR-SUS-ISG displayed favorable shear dilution properties, reducing viscosity at ambient temperature, enhancing fluidity, and facilitating convenient packaging and transport. Biocompatibility assessments on both human corneal epithelial cells and rabbit eyes demonstrated that SR-SUS-ISG could well be tolerated. Pharmacokinetic investigations in rabbit ocular aqueous humor revealed sustained release, improved corneal penetration, and enhanced bioavailability. Additionally, in a rat corneal alkali burn model, SR-SUS-ISG exhibited inhibitory effects on corneal neovascularization, associated with decreased levels of the inflammatory factors VEGF and MMPs. These findings suggested that SR-SUS-ISG held promise as an effective ocular drug delivery system.