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Background: Efgartigimod (Efgartigimod alpha fcab, Vyvgart™) is a pioneering neonatal Fc receptor (FcRn) antagonist for the treatment of severe autoimmune diseases mediated by pathogenic immunoglobulin G (IgG) autoantibodies, including myasthenia gravis (MG). It is a well-tolerated drug with minor side effects, such as headache and upper respiratory (lung) and urinary tract infections. Here, we present a case of Kaposi's varicelliform eruption (KVE) and herpetic conjunctivitis related to efgartigimod in a 60-year-old patient with ocular MG (OMG). Case description: A 60-year-old Chinese male suffered from acetylcholine receptor antibody positive (AChR Ab+) OMG for 8 years. During this period, he underwent first-line treatment with systemic corticosteroids, cyclosporine, cyclophosphamide, and so on, but had poor symptom improvement. On the recommendation of his attending neurologist, he received one cycle of intravenous efgartigimod (10mg/kg, once weekly for 4 weeks). The patient experienced fever, widespread painful blisters, and edema on the face on the third day after his last intravenous infusion. The patient also complained of increased secretions and a foreign body sensation in both eyes. Laboratory tests confirmed infection with herpes simplex virus (HSV). A diagnosis of efgartigimod-associated KVE and herpetic conjunctivitis was made. After intravenous administration (5mg/kg, 3 times a day, every 8 hours) for 10 days, the patient was cured without residual complications. Conclusions: This case is the first report of a patient with KVE and herpetic conjunctivitis related to efgartigimod in PubMed. This is rare and unusual. Clinicians should be alert to the rare symptoms related to efgartigimod. [ABSTRACT FROM AUTHOR]

To uncover the regulatory metabolism of poly-glutamic acid (PGA) in protecting wheat crops against salt stress (SS) at the physiological level, we utilised hydroponic experiments to explore the roles of PGA in regulating the photosynthetic performance, water physiology, antioxidant metabolism and ion homeostasis of wheat seedlings exposed to SS for 10 days. The findings demonstrated that SS inhibited the photosynthetic performance of wheat seedlings. In contrast, different doses of PGA all improved the photosynthetic performance, especially for 0.3% PGA. Compared with SS, 0.3% PGA plus SS decreased nonphotochemical quenching (qN) by 26.3% and respectively increased photosynthetic rate (Pn), soil and plant analyser development (SPAD) value, maximum photochemical efficiency of photosystem II (PSII) (Fv/Fm), photochemical quenching (qP) and actual photochemical efficiency of PSII (Y(II)) by 54.0, 27.8, 34.6, 42.4 and 25.8%. For water metabolism, SS destroyed the water balance of wheat seedlings. In contrast, different doses of PGA enhanced water balance, especially for 0.3% PGA. Compared with SS, 0.3% PGA plus SS decreased leaf water saturation deficit (LWSD) by 35.5% and respectively increased leaf relative water content (LRWC), transpiration rate (Tr), stomatal conductance (gs) and the contents of soluble sugars (SSS) and proline (Pro) by 15.9, 94.7, 37.5, 44.6 and 62.3%. For antioxidant metabolism, SS induced the peroxide damage to wheat seedlings. In contrast, different doses of PGA all mitigated the SS-induced peroxide damage, especially for 0.3% PGA. Compared with SS, 0.3% PGA plus SS respectively decreased superoxide anion (O2-), hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents and electrolyte leakage (EL) by 39.1, 29.6, 46.2 and 36.3%, and respectively increased superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), dehydroascorbate reductases (DHAR) and monodehydroascorbate reductase (MDHAR) activities, and antioxidants ascorbic acid (AsA) and glutathione (GSH) contents by 69.2, 49.2, 77.8, 80.6, 109.5, 121.7, 104.5, 63.8 and 39.6%. Besides, SS destroyed the ion homeostasis of wheat seedlings. In contrast, different doses of PGA all maintained ion homeostasis, especially for 0.3% PGA. Compared with SS, 0.3% PGA plus SS reduced Na+ content by 40.7% and respectively increased K+, Ca2+ and Mg2+ contents by 64.4, 82.6 and 105.6%, thereby respectively increasing K+/Na+, Ca2+/Na+ and Mg2+/Na+ ratios by 177.6, 209.4 and 244.8%. In the above ways, SS inhibited wheat height and biomass. In contrast, different doses of PGA all improved wheat height and biomass under SS, especially for 0.3% PGA. Compared with SS, 0.3% PGA plus SS, respectively, increased wheat height and biomass by 27.4% and 41.7%. In the above ways, PGA mitigated salt toxicity in wheat seedlings. The current findings implied that there was a potential for the use of PGA in real situations to improve wheat salt tolerance, especially for the 0.3% dose. [ABSTRACT FROM AUTHOR]

Objective: Previous research has shown that human identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promote coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA). However, the association of HA with mortality and long COVID in SARS-CoV-2 reinfection and first infection is unclear. Methods: Patients with COVID-19 at Beijing Ditan Hospital from September 2023 to November 2023 were consecutively enrolled. SARS-CoV-2 reinfections were matched 1:2 with first infections using a nearest neighbor propensity score matching algorithm. We compared the hospital outcomes between patients with COVID-19 reinfection and first infection. The association between HA levels and mortality and long COVID in the matched cohort was analyzed. Results: The reinfection rate among COVID-19 hospitalized patients was 25.4% (62 cases). After propensity score matching, we found that reinfection was associated with a better clinical course and prognosis, including lower levels of C-reactive protein and erythrocyte sedimentation rate, fewer cases of bilateral lung infiltration and respiratory failure, and shorter viral clearance time and duration of symptoms (p < 0.05). HA levels were significantly higher in patients with primary infection [128.0 (90.5, 185.0) vs. 94.5 (62.0, 167.3), p = 0.008], those with prolonged viral clearance time [90.5 (61.5, 130.8) vs. 130.0 (95.0, 188.0), p < 0.001], and deceased patients [105.5 (76.8, 164.5) vs. 188.0 (118.0, 208.0), p = 0.002]. Further analysis showed that HA was an independent predictor of death (AUC: 0.789), and the risk of death increased by 4.435 times (OR = 5.435, 95% CI = 1.205-24.510, p = 0.028) in patients with high HA levels. We found that patients with HA levels above 116 ng/mL had an increased risk of death. However, the incidence of long COVID was similar in the different HA level groups (p > 0.05). Conclusion: Serum HA may serve as a novel biomarker for predicting COVID-19 mortality in patients with SARS-CoV-2 reinfection and first infection. However, HA levels may not be associated with long COVID. [ABSTRACT FROM AUTHOR]

Objective: Inflammation contributes to the development of metabolic bone diseases. The C-reactive protein-to-albumin ratio (CAR) is an inflammationbased marker with a prognostic value for several metabolic diseases. This study investigated the relationship between the CAR and osteoporosis (OP) in patients with primary biliary cholangitis (PBC). Methods: Patients with PBC treated at Beijing Ditan Hospital between January 2018 and June 2023 were enrolled. Logistic regression analysis was performed to investigate the factors influencing OP. The predictive value of CAR for OP was evaluated using receiver operating characteristic (ROC) curves. Moreover, a restricted cubic spline (RCS) fitted with a logistic regression model was used to analyze the relationship between CAR and OP. Results: The prevalence of OP among the patients with PBC was 26.9% (n = 82). CAR levels were higher in the OP group than in the non-OP group (0.33 (0.09, 0.61) vs. 0.08 (0.04, 0.18), P < 0.001). Logistic regression analysis showed that CAR was an independent predictor of OP in patients with PBC (odds ratio = 2.642, 95% confidence interval = 1.537-4.540, P < 0.001). CAR exhibited a good predictive ability for OP, with an areas under the curve (AUC) of 0.741. We found that individuals with CAR values > 0.1 have higher odds of OP. In addition, high CAR levels were associated with an increased prevalence of fragility fractures and high 10-year fracture risk. Conclusion: High CAR levels were associated with greater odds of developing OP, and the CAR could serve as an independent predictor of OP in patients with PBC. [ABSTRACT FROM AUTHOR]

Background: The long-term prognosis of heart failure with preserved ejection fraction (HFpEF) is influenced by malnutrition. Currently, there's a deficit in objective and comprehensive nutritional assessment methods to evaluate the nutritional status and predicting the long-term outcomes of HFpEF patients. Methods: Our retrospective study included two hundred and eighteen elderly HFpEF patients admitted to the cardiovascular ward at the Air Force Medical Centre from January 2016 to December 2021. Based on follow-up outcomes, patients were categorized into all-cause death (99 cases) and Survival (119 cases) groups. We compared general data, laboratory results, and nutritional indexes between groups. Differences in subgroups based on Triglyceride-Total Cholesterol-Body Weight Index (TCBI), Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlled Nutrition Score (CONUT) were analyzed using Kaplan-Meier survival curves and log-rank test. COX regression was used to identify all-cause mortality risk factors, and the predictive accuracy of the four nutritional indices was assessed using receiver operating characteristic (ROC) curves and Delong test analysis. Results: A total of 101 (45.41%) HFpEF patients experienced all-cause mortality during 59.02 ± 1.79 months of follow-up. The all-cause mortality group exhibited lower GNRI and PNI levels, and higher CONUT levels than the Survival group (p < 0.05). Kaplan-Meier analysis revealed lower cumulative survival in the low GNRI (≤96.50) and low PNI (≤43.75) groups, but higher in the low CONUT (≤2) group, compared to their respective medium and high-value groups. Multifactorial COX regression identified low PNI (≤43.75) as an independent all-cause mortality risk factor in elderly HFpEF patients. ROC and Delong's test indicated PNI (area under the curve [AUC] = 0.698, 95% confidence interval [CI] 0.629-0.768) as a more effective predictor of all-cause mortality than TCBI (AUC = 0.533, 95% CI 0.456-0.610) and CONUT (AUC = 0.621, 95% CI 0.547-0.695; p < 0.05). However, there was no significant difference compared to GNRI (AUC = 0.663, 95% CI 0.590-0.735; p > 0.05). Conclusions: In elderly HFpEF patients a PNI ≤43.75 was identified as an independent risk factor for all-cause mortality. Moreover, PNI demonstrates superior prognostic performance in predicting all-cause mortality in elderly patients with HFpEF when compared to TCBI, GNRI, and COUNT. [ABSTRACT FROM AUTHOR]

Coxsackievirus B1 (CVB1), an enterovirus with multiple clinical presentations, has been associated with potential long‐term consequences, including hand, foot, and mouth disease (HFMD), in some patients. However, the related animal models, transmission dynamics, and long‐term tissue tropism of CVB1 have not been systematically characterized. In this study, we established a model of CVB1 respiratory infection in rhesus macaques and evaluated the clinical symptoms, viral load, and immune levels during the acute phase (0–14 days) and long‐term recovery phase (15–30 days). We also investigated the distribution, viral clearance, and pathology during the long‐term recovery period using 35 postmortem rhesus macaque tissue samples collected at 30 days postinfection (d.p.i.). The results showed that the infected rhesus macaques were susceptible to CVB1 and exhibited HFMD symptoms, viral clearance, altered cytokine levels, and the presence of neutralizing antibodies. Autopsy revealed positive viral loads in the heart, spleen, pancreas, soft palate, and olfactory bulb tissues. HE staining demonstrated pathological damage to the liver, spleen, lung, soft palate, and tracheal epithelium. At 30 d.p.i., viral antigens were detected in visceral, immune, respiratory, and muscle tissues but not in intestinal or neural tissues. Brain tissue examination revealed viral meningitis‐like changes, and CVB1 antigen expression was detected in occipital, pontine, cerebellar, and spinal cord tissues at 30 d.p.i. This study provides the first insights into CVB1 pathogenesis in a nonhuman primate model of HFMD and confirms that CVB1 exhibits tissue tropism following long‐term infection. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of death and disability in the world. Astrocytes are special glial cells within the central nervous system and play important roles in mediating neuroprotection and repair processes during stroke. Extracellular vesicles (EVs) are lipid bilayer particles released from cells that facilitate intercellular communication in stroke by delivering proteins, lipids, and RNA to target cells. Recently, accumulating evidence suggested that astrocyte-derived EVs (ADEVs) are actively involved in mediating numerous biological processes including neuroprotection and neurorepair in stroke and they are realized as an excellent therapeutic approach for treating stroke. In this review we systematically summarize the up-to-date research on ADEVs in stroke, and prospects for its potential as a novel therapeutic target for stroke. We also provide an overview of the effects and functions of ADEVs on stroke recovery, which may lead to developing clinically relevant therapies for stroke. [ABSTRACT FROM AUTHOR]

Coxsackievirus B3 (CVB3) is the pathogen causing hand, foot and mouth disease (HFMD), which manifests across a spectrum of clinical severity from mild to severe. However, CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis, failing to replicate human HFMD symptoms. Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys, there is no comprehensive data on CVB3. In this study, we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes. The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip, leading to nasopharyngeal colonization, acute severe pathological injury, and typical HFMD symptoms. Notably, the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage. In the subsequent study, rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms, viral excretion, serum antibody conversion, viral nucleic acids and antigens, and the specific organ damages, particularly in the heart. Surprisingly, there were no significant differences in myocardial enzyme levels, and the clinical symptoms resembled those often associated with common, mild infections. In summary, the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD. These models could serve as a basis for understanding the disease pathogenesis, conducting pre-trial prevention and evaluation, and implementing post-exposure intervention. [ABSTRACT FROM AUTHOR]

Aim: We investigated the effect of lifespan cognitive reserve and its components on cognitive frailty among older adults. Methods: A total of 4922 participants aged =65 years were recruited in 2008 and were followed up in 2011 from the Chinese Longitudinal Healthy Longevity Survey. Cognitive frailty was determined through the simultaneous presence of physical frailty (pre-frailty or frailty) and mild cognitive impairment, excluding concurrent dementia. The assessment of physical frailty and mild cognitive impairment was based on the Fatigue, Resistence, Ambulation, Illness, Loss of weight (FRAIL) (Fatigue, Resistence, Ambulation, Illness, Loss) and Mini-Mental State Examination scale, respectively. The lifespan cognitive reserve consisted of education attainment, occupational complexity and later-life leisure activities. We used logistic regression models to estimate the risk of cognitive frailty associated with the lifespan cognitive reserve and its components. Results: A higher level of lifespan cognitive reserve, higher educational attainment or leisure activities engagement, but not occupational complexity, were associated with lower risk of incident cognitive frailty. Furthermore, cognitive, social and physical activities were associated with lower risk of incident cognitive frailty. Conclusion: Cognitive reserve, particularly educational attainment and leisure activities, can protect from cognitive frailty. This implicates that individuals should accumulate cognitive reserve in their lifespan, and older adults should actively participate in leisure activities to prevent cognitive frailty. [ABSTRACT FROM AUTHOR]

Cellular senescence and iron accumulation were separately observed in diabetic nephropathy (DN). Limited evidence supports that iron was significantly accumulated in senescent cells. We aimed to explore whether iron is involved in the pathogenesis role of senescence in DN. Renal cells were treated with high glucose (HG, 35 mM) for 10 or 15 days, and DN mice were induced by high-fat diet and streptozotocin. Gene ontology enrichment, gene set enrichment analysis analysis, β-galactosidase staining, 5-ethynyl-2-deoxyuridine staining, and western blot depicted the upregulated senescence pathway in vitro and in vivo of DN. Lactate dehydrogenase (LDH) release was increased by HG and reversed by p16/p21 knockdown, and the supernatant of HG-treated cells caused increased LDH release from normal cells. Iron metabolism-related protein expression was disordered after HG exposure concomitant with senescence. Ferric ammonium citrate (50 μM) upregulated gamma-H2A.X variant histone and increased the senescence markers in HG-treated cells. The treatment of deferoxamine (0.5 μM) had the opposite effect. Compared to the non-DN individual, increased ferritin and senescence markers were verified in DN mice and patients, and the co-localization of ferritin and senescence markers was observed by immunofluorescence. These results suggested that accumulated iron was correlated with aggravated DNA damage and accelerated senescence, and revealed the role of iron in the cellular senescence of diseases. [ABSTRACT FROM AUTHOR]

Introduction: Seasonal influenza A H3N2 viruses are constantly changing, reducing the eectiveness of existing vaccines. As a result, the World Health Organization (WHO) needs to frequently update the vaccine strains to match the antigenicity of emerged H3N2 variants. Traditional assessments of antigenicity rely on serological methods, which are both labor-intensive and time-consuming. Although numerous computational models aim to simplify antigenicity determination, they either lack a robust quantitative linkage between antigenicity and viral sequences or focus restrictively on selected features. Methods: Here, we propose a novel computational method to predict antigenic distances using multiple features, including not only viral sequence attributes but also integrating four distinct categories of features that significantly aect viral antigenicity in sequences. Results: This method exhibits low error in virus antigenicity prediction and achieves superior accuracy in discerning antigenic drift. Utilizing this method, we investigated the evolution process of the H3N2 influenza viruses and identified a total of 21 major antigenic clusters from 1968 to 2022. Discussion: Interestingly, our predicted antigenic map aligns closely with the antigenic map generated with serological data. Thus, our method is a promising tool for detecting antigenic variants and guiding the selection of vaccine candidate. [ABSTRACT FROM AUTHOR]

Let Fq be the finite field of order q where q = pk, k is a positive integer and p is an odd prime. Let F*q represent the nonzero elements of Fq. For f(x1,···,xn) ∊ Fq[x1,···,xn], we used N(f(x1,···,xn) = 0) to denote the number of Fq-rational points of the affine hypersurface f(x1,···,xn) = 0. In 2020, Zhao et al. obtained the explicit formulae for N(x41 + x42 = c), N(x41 + x42+ x43 = c) and N(41+ x42+ x43+ x44 = c) over Fq, with c ∊ F*q. In this paper, by using Jacobi sums and an analog of the Hasse-Davenport theorem, we arrived at explicit formulae for N(a1x41 + a2x42 = c) and N(b1x41 + b2x42 + b3x43 = c) with ai, bj ∊ F*q(1 ≤ i ≤ 2, 1 ≤ j ≤ 3) and c ∊ Fq. Furthermore, by using the reduction formula for Jacobi sums, the number of rational points of the quartic diagonal hypersurface a1x41 + a2x42 +···+ anx4n = c of n ≥ 4 variables with ai ∊ F*q (1 ≤ i ≤ n), c ∊ Fq and p = 1(mod 4), can also be deduced. These extended and improved earlier results. [ABSTRACT FROM AUTHOR]

The job shop scheduling problem is a classical combinatorial optimization challenge frequently encountered in manufacturing systems. It involves determining the optimal execution sequences for a set of jobs on various machines to maximize production efficiency and meet multiple objectives. The Non-dominated Sorting Genetic Algorithm III (NSGA-III) is an effective approach for solving the multi-objective job shop scheduling problem. Nevertheless, it has some limitations in solving scheduling problems, including inadequate global search capability, susceptibility to premature convergence, and challenges in balancing convergence and diversity. To enhance its performance, this paper introduces a strengthened dominance relation NSGA-III algorithm based on differential evolution (NSGA-III-SD). By incorporating constrained differential evolution and simulated binary crossover genetic operators, this algorithm effectively improves NSGA-III's global search capability while mitigating premature convergence issues. Furthermore, it introduces a reinforced dominance relation to address the tradeoff between convergence and diversity in NSGA-III. Additionally, effective encoding and decoding methods for discrete job shop scheduling are proposed, which can improve the overall performance of the algorithm without complex computation. To validate the algorithm's effectiveness, NSGA-III-SD is extensively compared with other advanced multi-objective optimization algorithms using 20 job shop scheduling test instances. The experimental results demonstrate that NSGA-III-SD achieves better solution quality and diversity, proving its effectiveness in solving the multi-objective job shop scheduling problem. [ABSTRACT FROM AUTHOR]

The development of an effective method for predicting the transfer of biologics from plasma into breast milk is important to ensure the safe use of medications during lactation. The aim of this study was to develop a regression model that could predict the transfer of monoclonal antibodies (mAbs) and Fc-fusion proteins from plasma into breast milk. By searching various databases, a list of eleven mAbs and Fc-fusion proteins with available information of presence in the breast milk was generated. Physicochemical properties such as the isoelectric point (pI), molecular weight (MW), dissociation constant (Kd), and pharmacokinetic (PK) parameters such as clearance (CL), volume of distribution (Vd), and half-life (T1/2) were collected or calculated. A twovariable non-linear regression analysis and a multivariate regression analysis were employed to establish correlation of milk-to-plasma (M/P) ratios with different combinations of two physicochemical properties. The 3D isoelectric point (pI) of the Fv region and the buried surface area (BSA) between the light and heavy chains (LC_HC) were two factors that emerged as a promising predictor of the milk-to-plasma concentration ratio (M/P). The correlation between M/P ratio, 3D pI of Fv region, and BSA_LC_HC was found to be good with R2 of 0.9058. Other combinations of the physicochemical properties did not show a statistically significant correlation. The multivariate regression model was used to predict the MP ratios for 79 different mAbs. We believe that this regression model could serve as a valuable tool to estimate the M/P ratios of mAbs and Fc-fusion proteins. Further model validation is necessary when the M/P ratios of additional biologics are available. This could inform clinical decision-making and improve the safety of large molecule drug use during lactation. [ABSTRACT FROM AUTHOR]

Precessing vortex rope (PVR) plays a key role in inducing hydraulic resonance in Francis turbines operating at partial load, possibly degrading power plant stability and availability. Air injection into the runner cone is a suitable mitigating alternative; however, the influence mechanism of air injection on PVR remains unclear. The principal objective of this study was to establish response relationships between the characteristic parameters and air injection by the method of computational fluid dynamics (CFD) considering the fluid components of water, water vapour and air. The findings show that cavitation flow can be completely suppressed by slight air injection; however, the helical vortex structures are persisted at 1.0% and 2.0% air volume fractions, and the static pressure recovery is improved together with a slight increase in the hydraulic loss. At 3.0% air volume fraction, the vortex structure completely disappears, leaving an umbrella-shaped structure, with no pressure vibration arising in the turbine. Moreover, the physical mechanism of reducing the pressure amplitudes is clarified. This results clarify the influence mechanism of air injection on PVR, and contribute to steadily extending the flexibility of the operating range of the turbine during the engineering application. [ABSTRACT FROM AUTHOR]

Background: Shoulder-hand syndrome (SHS) is a common complication after stroke, and SHS-induced pain significantly hampers patients' overall recovery. As an alternative therapy for pain relief, acupuncture has certain advantages in alleviating pain caused by SHS after stroke. However, choosing the best treatment plan from a variety of acupuncture options is still a serious challenge in clinical practice. Therefore, we conducted this Bayesian network meta-analysis to comprehensively compare the effectiveness of various acupuncture treatment methods. Methods: We systematically searched for randomized controlled trials (RCTs) of acupuncture treatment in patients with post-stroke SHS published in PubMed, Embase, Cochrane, and Web of Science until 9 March 2023. We used the Cochrane bias risk assessment tool to assess the bias risk in the included original studies. Results: A total of 50 RCTs involving 3,999 subjects were included, comprising 19 types of effective acupuncture interventions. Compared to single rehabilitation training, the top three interventions for VAS improvement were floating needle [VAS = -2.54 (95% CI: -4.37 to -0.69)], rehabilitation + catgut embedding [VAS = -2.51 (95% CI: -4.33 to -0.68)], and other multi-needle acupuncture combinations [VAS = -2.32 (95% CI: -3.68 to -0.94)]. The top three interventions for improving the Fugl-Meyer score were eye acupuncture [Meyer = 15.73 (95% CI: 3.4627.95)], other multi-needle acupuncture combinations [Meyer = 12.22 (95% CI: 5.1919.34)], and traditional western medicine + acupuncture + traditional Chinese medicine [Meyer = 11.96 (95% CI: -0.59 to 24.63)]. Conclusion: Multiple acupuncture methods are significantly effective in improving pain and upper limb motor function in post-stroke SHS, with relatively few adverse events; thus, acupuncture can be promoted. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, CRD42023410957. [ABSTRACT FROM AUTHOR]

Background: Accurate detection of atrial fibrillation (AF) recurrence after catheter ablation is crucial. In this study, we aimed to conduct a systematic review of machine-learning-based recurrence detection in the relevant literature. Methods: We conducted a comprehensive search of PubMed, Embase, Cochrane, and Web of Science databases from 1980 to December 31, 2022 to identify studies on prediction models for AF recurrence risk after catheter ablation. We used the prediction model risk of bias assessment tool (PROBAST) to assess the risk of bias, and R4.2.0 for meta-analysis, with subgroup analysis based on model type. Results: After screening, 40 papers were eligible for synthesis. The pooled concordance index (C-index) in the training set was 0.760 (95% confidence interval [CI] 0.739 to 0.781), the sensitivity was 0.74 (95% CI 0.69 to 0.77), and the specificity was 0.76 (95% CI 0.72 to 0.80). The combined C-index in the validation set was 0.787 (95% CI 0.752 to 0.821), the sensitivity was 0.78 (95% CI 0.73 to 0.83), and the specificity was 0.75 (95% CI 0.65 to 0.82). The subgroup analysis revealed no significant difference in the pooled C-index between models constructed based on radiomics features and those based on clinical characteristics. However, radiomics based showed a slightly higher sensitivity (training set: 0.82 vs. 0.71, validation set: 0.83 vs. 0.73). Logistic regression, one of the most common machine learning (ML) methods, exhibited an overall pooled C-index of 0.785 and 0.804 in the training and validation sets, respectively. The Convolutional Neural Networks (CNN) models outperformed these results with an overall pooled C-index of 0.862 and 0.861. Age, radiomics features, left atrial diameter, AF type, and AF duration were identified as the key modeling variables. Conclusions: ML has demonstrated excellent performance in predicting AF recurrence after catheter ablation. Logistic regression (LR) being the most widely used ML algorithm for predicting AF recurrence, also showed high accuracy. The development of risk prediction nomograms for wide application is warranted. [ABSTRACT FROM AUTHOR]

Self-healing is a bioinspired strategy to repair damaged conductors under repetitive wear and tear, thereby largely extending the life span of electronic devices. The self-healing process often demands external triggering conditions as the practical challenges for the widespread applications. Here, a compliant conductor with electrically self-healing capability is introduced by combining ultrahigh sensitivity to minor damages and reliable recovery from ultrahigh tensile deformations. Conductive features are created in a scalable and low-cost fabrication process comprising a copper layer on top of liquid metal microcapsules. The efficient rupture of microcapsules is triggered by structural damages in the copper layer under stress conditions as a result of the strong interfacial interactions. The liquid metal is selectively filled into the damaged site for the instantaneous restoration of the metallic conductivity. The unique healing mechanism is responsive to various structural degradations including microcracks under bending conditions and severe fractures upon large stretching. The compliant conductor demonstrates high conductivity of ~12,000 S/cm, ultrahigh stretchability of up to 1,200% strain, an ultralow threshold to activate the healing actions, instantaneous electrical recovery in microseconds, and exceptional electromechanical durability. Successful implementations in a light emitting diode (LED) matrix display and a multifunctional electronic patch demonstrate the practical suitability of the electrically self-healing conductor in flexible and stretchable electronics. The developments provide a promising approach to improving the self-healing capability of compliant conductors. [ABSTRACT FROM AUTHOR]

Climatic warming is promoting change of a very diverse nature in the biological events of an array of insect species, including alterations in phenology. Based on collected historical data, the potential impacts of climate warming on the phenology of Bactrocera dorsalis (Hendel) (Diptera Tephritidae) in Fujian and Guangxi, China were investigated by analysing the four phenological parameters including the date of first occurrence, end occurrence, population initial growth and population peak. Results showed that, during a period of last three decades (1990-2020), the annual and seasonal mean temperatures of Guangxi and Fujian have shown increasing trends at different levels. During these studied periods, the end occurrence date and population peak of B. dorsalis in Fujian significantly advanced, and first occurrence of B. dorsalis in Guangxi also significantly moved earlier. Pearson correlation analysis suggested that the mean temperature in winter and spring were the key temperature variables affecting the occurrence and population growth of B. dorsalis in Fujian and Guangxi, respectively. This research provides valuable implications for understanding the effects of climate warming on insect pests and theoretical guidance for prediction and control of fruit fly pests in the future. [ABSTRACT FROM AUTHOR]

Objective: Ursodeoxycholic acid (UDCA) may reduce susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by downregulating angiotensin-converting enzyme 2 (ACE2), based on recent experimental investigation. This study aimed to determine the potential protective effect of UDCA against SARS-CoV-2 infection in patients with chronic liver disease. Methods: Patients with chronic liver disease receiving UDCA (taking UDCA ≥1 month) at Beijing Ditan Hospital between January 2022 and December 2022 were consecutively enrolled. These patients were matched in a 1:1 ratio to those with liver disease not receiving UDCA during the same period by using a propensity score matching analysis with nearest neighbor matching algorithm. We conducted a phone survey of coronavirus disease 2019 (COVID-19) infection during the early phase of the pandemic liberation (from 15 December 2022 to 15 January 2023). The risk of COVID-19 was compared in two matched cohorts of 225 UDCA users and 225 non-UDCA users based on patient self-report. Results: In the adjusted analysis, the control group was superior to the UDCA group in COVID-19 vaccination rates and liver function indicators, including γ-glutamyl transpeptidase and alkaline phosphatase (p < 0.05). UDCA was associated with a lower incidence of SARS-CoV-2 infection (UDCA 85.3% vs. control 94.2%, p = 0.002), more mild cases (80.0% vs. 72.0%, p = 0.047), and shorter median time from infection to recovery (5 vs. 7 days, p < 0.001). Logistic regression analysis showed that UDCA was a significant protective factor against COVID-19 infection (OR: 0.32, 95%CI: 0.16–0.64, p = 0.001). Furthermore, diabetes mellitus (OR: 2.48, 95%CI: 1.11–5.54, p = 0.027) and moderate/severe infection (OR: 8.94, 95%CI: 1.07–74.61, p = 0.043) were more likely to prolong the time from infection to recovery. Conclusion: UDCA therapy may be beneficial in reducing COVID-19 infection risk, alleviating symptoms, and shortening the recovery time in patients with chronic liver disease. However, it should be emphasized that the conclusions were based on patient self-report rather than classical COVID-19 detection by experimental investigations. Further large clinical and experimental studies are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases have threatened human health, amongst which coronary heart disease (CHD) is the third most common cause of death. CHD is considered to be a metabolic disease; however, there is little research on the CHD metabolism. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has enabled the development of a suitable nanomaterial that can be used to obtain considerable high-quality metabolic information without complex pretreatment of biological fluid samples. This study combines SiO2@Au nanoshells with minute plasma to obtain metabolic fingerprints of CHD. The thickness of the SiO2@Au shell was also optimized to maximize the laser desorption/ionization effect. The results demonstrated 84% sensitivity at 85% specificity for distinguishing CHD patients from controls in the validation cohort. [ABSTRACT FROM AUTHOR]

Purpose The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective response, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number. [ABSTRACT FROM AUTHOR]

Education research is increasingly focused on fostering self-regulated learning (SRL) and socially shared regulation of learning (SSRL) among students. However, previous meta-analyses have rarely focused on the specific types of regulated learning scaffolding. Therefore, this meta-analysis examines the effects of different types of regulated learning scaffolding on regulation strategies and academic performance. A total of 46 articles met the inclusion criteria and were included in the final analysis. The findings showed that overall, regulated learning scaffolding had a moderate effect (g = 0.587). In addition, moderation analyses were performed using a random effects model that focused on four types of scaffolding. The results showed that overall, composite tools had the greatest effect, while the most useful scaffolding for SRL and SSRL were group awareness tools (g = 0.61) and composite tools (g = 0.53), respectively. In terms of learning outcomes, composite tools had the greatest effect on regulation strategies, while intelligent pedagogical agents had the greatest effect on academic performance. We also performed a meta-regression analysis to identify the moderators that had the greatest influence on the effects of regulated learning scaffolding. The results showed that grade level, academic subject, and cooperation all had a significant impact. In conclusion, these findings provide evidence for validating the effectiveness of four regulated learning scaffolding and for discovering their function for SSRL, and presented some practical implications of our findings. [ABSTRACT FROM AUTHOR]

Antibody-based therapies that inhibit pro-inflammatory cytokine signalling are commonly used in dermatology. Paradoxically, these biological agents may induce or exacerbate paradoxical reactions. Recently, it has been reported that the treatment of eczema with dupilumab can lead to the development of psoriasiform eruptions, which we called psoriasiform paradoxical reactions (P-PRs). Conversely, cases of eczematous paradoxical reactions (E-PRs) have also been described in patients with psoriasis treated with biologics. To summarise the case characteristics and disease features of phenotypic transition between psoriasis and eczematoid dermatitis, and to explore the mechanism or connection related to biological agents or patients' genetic characteristics, a systematic review was conducted for P-PRs in atopic dermatitis and E-PRs in patients with psoriasis treated with corresponding biological agents, respectively. We identified a series of P-PRs in 42 atopic dermatitis cases treated with dupilumab. The time to onset of P-PRs typically ranged from weeks to months, with a mean latency period of 22.65 weeks. Almost all patients presented with new-onset P-PRs. Simultaneously, we reviewed 22 articles reporting 51 patients with psoriasis with biological agent-induced E-PRs, which occurred on average at 24.47 weeks, 72.55% of them induced by IL-17A inhibitors. 48.98% (24/49) of cases reported a positive personal history of atopy, which may suggest an increased risk of biological agent-induced paradoxical eruptions. Overall, the improvement or resolution upon discontinuation of the inciting biologics was relatively common, and further studies are needed to estimate the real prevalence and unveil the pathophysiological mechanisms of these paradoxical events. [ABSTRACT FROM AUTHOR]

High temperature in summer is an unfavorable factor for passion fruit (Passiflora edulis), which can lead to restricted growth, short flowering period, few flower buds, low fruit setting rate, severe fruit drop, and more deformed fruit. To explore the molecular physiology mechanism of passion fruit responding to high-temperature stress, we use 'Zhuangxiang Mibao', a hybrid passion fruit cultivar, as the test material. Several physiological indicators were measured and compared between high-temperature (average temperature 38 °C) and normal temperature (average temperature 25 °C) conditions, including photosynthesis, chlorophyll fluorescence parameters, peroxidase activity (POD), superoxide dismutase activity (SOD) and malondialdehyde content. We performed RNA-seq analysis combined with biochemistry experiment to investigate the gene and molecular pathways that respond to high-temperature stress. The results showed that some physiological indicators in the high-temperature group, including the net photosynthetic rate, stomatal conductance, intercellular CO2 concentration, transpiration rate, and the maximum chemical quantum yield of photosystemII (PSII), were significantly lower than those of the control group. Malondialdehyde content was substantially higher than the control group, while superoxide dismutase and superoxide dismutase activities decreased to different degrees. Transcriptome sequencing analysis showed that 140 genes were up-regulated and 75 genes were down-regulated under high-temperature stress. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analysis of differentially expressed genes revealed many metabolic pathways related to high-temperature stress. Further investigation revealed that 30 genes might be related to high-temperature stress, such as chlorophyllide a oxygenase (CAO), glutathione (GSH), WRKY transcription factors (WRKY), and heat shock protein (HSP), which have also been reported in other species. The results of real-time fluorescence quantitative PCR and RNA-seq of randomly selected ten genes are consistent, which suggests that the transcriptome sequencing results were reliable. Our study provides a theoretical basis for the mechanism of passion fruit response to high-temperature stress. Also, it gives a theoretical basis for the subsequent breeding of new heat-resistant passion fruit varieties. [ABSTRACT FROM AUTHOR]

Combining physiological measures with observational data (e.g., video or self-reports) to further capture and understand the temporal and cyclical process of social regulation has become a trend in the field. Synchronized physiological arousal is a particularly meaningful situation in collaboration. However, little attention has been given to synchronized physiological arousal episodes and their relationship with the social regulatory process. In addition, only a few research utilized heart rate (HR) as a physiological measure in the current collaboration literature. More research is necessary to reveal the potential of HR to expand the diversity of physiological indicators in the field. Therefore, the current study aimed to explore what synchronized physiological arousal can further reveal about the social regulatory process. To achieve this goal, this study designed a collaborative argumentation (CA) activity for undergraduates (mean age 20.3). It developed an arousal-regulation analysis platform, which could automatically detect synchronized physiological arousal in HR and align them with coding challenges and social regulation based on the timeline. In total, 14 four-member groups were recruited. After analyzing both videos and HR data, several findings were obtained. First, only one-third of episodes were synchronized physiological arousal episodes, and the situations where four members were all in arousal states were rare during CA. Second, synchronized physiological arousal was more sensitive to socio-emotional aspects of collaboration as the shared physiological arousal more frequently co-occurred with socio-emotional challenges and socio-emotional regulation, while it happened the least under motivational challenges. Third, synchronized physiological arousal has also been found to be associated with the challenges being regulated. Finally, pedagogical implications were suggested. [ABSTRACT FROM AUTHOR]

Intramuscular lipid deposition is important for meat quality improvement. microRNAs and their target mRNAs provide a new approach for studying the mechanism of fat deposition. The present study aimed to investigate the effect of miR-130b duplex (miR-130b-5p, miR-130b-3p) and its target gene KLF3 in regulating goat intramuscular adipocyte differentiation. Goat intramuscular preadipocytes were isolated from 7-d-old male Jianzhou big-ear goats and identified by Oil red O staining after differentiation induction. miR-130b-5p and miR-130b-3p mimics or inhibitors and their corresponding controls were transfected into goat intramuscular preadipocytes, respectively, and differentiation was induced by 50μM oleic acid for 48 h. Oil red O and Bodipy staining indicated that both miR-130b-5p and miR-130b-3p can reduce lipid droplets accumulation and triglyceride (TG) content (P < 0.01). Differentiation markers C/EBPα, C/EBPβ, PPARγ, pref1, fatty acids synthesis markers ACC, FASN, DGAT1, DGAT2, AGPAT6, TIP47, GPAM, ADRP, AP2, SREBP1, and TG markers LPL, ATGL, HSL were assessed by qPCR. All the markers measured were downregulated by miR-130b-5p and miR-130b-3p analog (P < 0.01), suggesting that miR-130b inhibits goat intramuscular adipocyte adipogenic differentiation, fatty acids synthesis, and lipid lipolysis. To examine the mechanism of miR-130b duplex inhibition of lipid deposition, TargetScan, miRDB, and starBase were used to predict the potential targets, KLF3 was found to be the only one intersection. Furthermore, the 3ʹUTR of KLF3 was cloned, qPCR analysis and dual luciferase activity assay showed that both miR-130b-5p and miR-130b-3p could directly regulate KLF3 expression (P < 0.01). In addition, overexpression and interference of KLF3 were conducted, it was found that KLF3 positively regulated lipid droplets accumulation by Oil red O, Bodipy staining, and TG content detection (P < 0.01). Quantitative PCR result indicated that KLF3 overexpression promoted lipid droplets accumulation relative genes C/EBPβ, PPARγ, pref1, ACC, FASN, DGAT1, DGAT2, AGPAT6, TIP47, GPAM, ADRP, SREBP1, LPL, and ATGL expression (P < 0.01). Downregulation of KLF3 inhibited the expression of genes such as C/EBPα, C/EBPβ, PPARγ, pref1, TIP47, GPAM, ADRP, AP2, LPL, and ATGL expression (P < 0.01). Taken together, these results indicate that miR-130b duplex could directly inhibit KLF3 expression, then attenuated adipogenic and TG synthesis genes expression, thus leading to its anti-adipogenic effect. [ABSTRACT FROM AUTHOR]

The disadvantages of the conventional model predictive current control method for the grid-connected converter (GCC) with an inductance-capacitance-inductance (LCL) filter are a large amount of calculation and poor parameter robustness. Once parameters of the model are mismatched, the control accuracy of model predictive control (MPC) will be reduced, which will seriously affect the power quality of the GCC. The article intuitively analyzes the sensitivity of parameter mismatch on the current predictive control of the conventional LCL-filtered GCC. In order to solve these issues, a model-free predictive current control (MFPCC) method for the LCL-filtered GCC is proposed in this paper. The contribution of this work is that a novel current predictive robust controller for the LCL-filtered GCC is designed based on the principle of the ultra-local model of a single input single output system. The proposed control method does not require using any model parameters in the controller, which can effectively suppress the disturbances of the uncertain parameter variations. Compared with conventional MPC, the proposed MFPCC has smaller current total harmonic distortion (THD). When the filter parameters are mismatched, the control error of the proposed method is smaller. Finally, a comparative experimental study is carried out on the platform of Typhoon and PE-Expert4 to verify the superiority and effectiveness of the proposed MFPCC method for the LCL-filtered GCC. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the major public health issues worldwide due to its high mortality and morbidity. Angiogenesis is the fundamental step of tumors transition from dormant to malignant state and it is recognized as one of the hallmarks of cancer. High mobility group AT-hook 2 encodes a small non-histone chromatin-associated protein that can modulate transcription by altering the chromatin architecture. Currently the mechanism by which high mobility group AT-hook 2 involved in angiogenesis in colorectal cancer has not been clarified. The expression of High mobility group AT-hook 2 was analyzed by immunohistochemistry, Western blotting and bioinformatics methods. cBioPortal and mExpress online tools were applied to explore the copy-number variation and methylation of high mobility group AT-hook 2 in colorectal cancer patients. Single cell data from gene expression omnibus was used to examine the specific cell type that contributed to the high mobility group AT-hook 2 expression in colorectal cancer. Lentivirus was used to knock down high mobility group AT-hook 2 in colorectal cancer cells and human umbilical vein endothelial cells was used to study angiogenesis. In the current study, we first detected the expression pattern of high mobility group AT-hook 2 in colorectal cancer patients and evaluated its clinical values and for the first time showed that copy number amplification contributed to the up regulation of high mobility group AT-hook 2 in colorectal cancer patients. By analyzing colorectal cancer single cell data we found that high mobility group AT-hook 2 was specifically up regulated in the colorectal epithelial cells. Furthermore, knocking down of high mobility group AT-hook 2 in colorectal cancer epithelial cells suppresses angiogenesis via dual regulation of vascular endothelial growth factor-A and semaphorin 3A in colorectal cancer through inactivating vascular endothelial growth factor receptor 2 pathway in human umbilical vein endothelial cells. High mobility group AT-hook 2 might be a promising prognostic marker and target for treating advanced colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Objective: Adipocyte differentiation is regulated by a variety of functional genes and noncoding RNAs. However, the role of miRNAs in lipid deposition of goat white adipose tissue is still unclear. Therefore, this study revealed the miRNA expression profile in goat subcutaneous adipocytes by sRNA-seq. Methods: The miRNA expressed in goat subcutaneous preadipocytes and the mature adipocytes were sequenced by sRNA-seq. The differentially expressed miRNAs (DEm) were screened and gene ontology (GO) and Kyoto encyclopedia for genes and genomes (KEGG) analyses were performed. Gain-of-function and loss-of-function combined with oil red O staining, Bodipy staining, and quantitative reverse-transcription polymerase chain reaction (qPCR) were utilized to determine the effect of miR-133a-3p on adipocyte differentiation. Results: A total of 218 DEm were screened out. The target genes of these DEm were significantly enriched in GO items such as biological regulation and in KEGG terms such as FAK signaling pathway and MAPK signaling pathway. qPCR verified that the expression trend of miRNA was consistent with miRNA-seq. The gain-of-function or loss-of-function of miR-133a-3p showed that it promoted or inhibited the accumulation of lipid droplets, and CCAAT enhancer binding protein α (C/EBPα) and C/EBPβ were extremely significantly up-regulated or down-regulated respectively (p<0.01), the loss-of-function also led to a significant down-regulation of peroxisome proliferator activated receptor gamma (PPARγ) (p<0.01). Conclusion: This study successfully identified miRNAs expression patterns in goat subcutaneous adipocytes, and functional identification indicates that miR-133a-3p is a positive regulator of the differentiation process of goat subcutaneous adipocytes. Our results lay the foundation for the molecular mechanism of lipid deposition in meat-source goats from the perspective of miRNA. [ABSTRACT FROM AUTHOR]

Background. Preoperative prediction of cervical lymph node metastasis in papillary thyroid carcinoma provided a basis for tumor staging and treatment decision. This study aimed to investigate the utility of machine learning and develop different models to preoperatively predict cervical lymph node metastasis based on ultrasonic radiomic features and clinical characteristics in papillary thyroid carcinoma nodules. Methods. Data from 400 papillary thyroid carcinoma nodules were included and divided into training and validation group. With the help of machine learning, clinical characteristics and ultrasonic radiomic features were extracted and selected using randomforest and least absolute shrinkage and selection operator regression before classified by five classifiers. Finally, 10 models were built and their area under the receiver operating characteristic curve, accuracy, sensitivity, specificity, positive predictive value and negative predictive value were measured. Results. Among the 10 models, RF-RF model revealed the highest area under curve (0.812) and accuracy (0.7542) in validation group. The top 10 variables of it included age, seven textural features, one shape feature and one first-order feature, in which eight were high-dimensional features. Conclusions. RF-RF model showed the best predictive performance for cervical lymph node metastasis. And the importance features selected by it highlighted the unique role of higher-dimensional statistical methods for radiomics analysis. [ABSTRACT FROM AUTHOR]

We demonstrate an ultra-broadband high temporal contrast infrared laser source based on cascaded optical parametric amplification, hollow-core fiber (HCF) and second harmonic generation processes. In this setup, the spectrum of an approximately 1.8 µm laser pulse has near 1 µm full bandwidth by employing an argon gas-filled HCF. Subsequently, after frequency doubling with cascaded crystals and dispersion compensation by a fused silica wedge pair, 9.6 fs (~3 cycles) and 150 µJ pulses centered at 910 nm with full bandwidth of over 300 nm can be generated. The energy stability of the output laser pulse is excellent with 0.8% (root mean square) over 20 min, and the temporal contrast is >1012 at -10 ps before the main pulse. The excellent temporal and spatial characteristics and stability make this laser able to be used as a good seed source for ultra-intense and ultrafast laser systems. [ABSTRACT FROM AUTHOR]

Temporal contrast directly affects the interaction between ultraintense and ultrashort pulse lasers with matter. Seed laser sources with broad bandwidth and high temporal contrast are significant for overall temporal contrast enhancement. The technique of cascaded nonlinear processes with optical parametric amplification and second-harmonic generation is demonstrated for high temporal contrast seed source generation. Within 40 ps before the main pulse, the temporal contrast reaches over 1011. The pulse energy and duration of the high-contrast pulse are 112 µJ and 70 fs, respectively. Considering its high beam quality and stability, this laser source can serve as a high-quality seed for Nd:glass-based ultraintense and ultrashort pulse laser facilities. [ABSTRACT FROM AUTHOR]

In recent years, the leaf beetle Galeruca daurica has broken out in the northern grasslands of Inner Mongolia, its management still mainly depends on chemical control using traditional insecticides or with novel action. The study was aim to identify mutation locus associated with resistance to diamide insecticides in field population of G. daurica, to provide a reference for rational selection of insecticides and to avoid the rapid resistance development to diamide insecticides. We cloned the full length of the ryanodine receptor gene of G. daurica (GdRyR), constructed 3D model and transmembrane regions by homologous modeling based on deduced amino acid sequence. Two potential mutation loci (Gly4911Glu and Ile4754Met) and allelic mutation frequencies were detected in individuals of G. daurica. In addition, their binding patterns to two diamide insecticides (chlorantraniliprole, cyantraniliprole) were analyzed separately using a molecular docking method. The full-length cDNA sequence of GdRyR (GenBank accession number: OP828593) was obtained by splicing and assembling, which is 15,399 bp in length and encodes 5,133 amino acids. The amino acid similarity of GdRyR with that of other Coleopteran insects were 86.70%-91.33%, which possessed the typical structural characteristics. An individual resistance allelic mutation frequency test on fifty field leaf beetles has identified 12% and 32% heterozygous individuals at two potential mutation loci Gly4911Glu and Ile4754Met, respectively. The affinity of the I4754M mutant model of GdRyR for chlorantraniliprole and cyantraniliprole was not significantly different from that of the wild type, and all had non-covalent interactions such as hydrogen bonding, hydrophobic interactions and π-cation interactions. However, the G4911E mutant model showed reduced affinity and reduced mode of action with two diamide insecticides, thus affecting the binding stability of the ryanodine receptor to the diamide insecticides. In conclusion, the G4911E mutation in GdRyR may be a potential mechanism for the development of resistance to diamide insecticides on G. daurica and should be a key concern for resistance risk assessment and reasonable applications of diamide insecticides for control in future. Moreover, this study could provide a reference for ryanodine receptor structure-based insecticides design. [ABSTRACT FROM AUTHOR]

Background: Head and neck squamous cell carcinoma (HNSCC) is a lifethreatening disease with poor prognosis. Pyroptosis has been recently disclosed as a programmed cell death triggered by invasive infection, involved in cancer development. However, the prognosis role of pyroptosis-related genes in HNSCC has not been discussed. Methods: The RNA sequence data of pyroptosis-related genes were obtained from The Cancer Genome Atlas (TCGA) database. Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis were performed to screen the HNSCC survival-related signature genes. We established a HNSCC risk model with the identified prognostic genes, then divided the HNSCC patients into low- and high-risk subgroups according to median risk score. Moreover, we utilized Gene Expression Omnibus (GEO) dataset to validate the risk model. Go and KEGG analyses were conducted to reveal the potential function of differential expression of genes that identified between low- and high-risk subgroups. ESTIMATE algorithm was performed to investigate the immune infiltration of tumors. Correlation between signature gene expression and drug- sensitivity was disclosed by Spearman's analysis. Results: We constructed a HNSCC risk model with identified seven pyroptosisrelated genes (CASP1, GSDME, IL6, NLRP1, NLRP2, NLRP6, and NOD2) as prognostic signature genes. High-risk subgroup of HNSCC patients in TCGA cohort correlated with lower survival probability than patients from low-risk subgroup (p < .001), and the result is verified with GEO dataset. In addition, 161 genes were identified differentially expressed between the low- and high-risk subgroups in the TCGA cohort, mainly related to immune response. Higher PD-L1 expression level was found in the high-risk subgroup that indicated the possible employment of immune checkpoint inhibitors. IL6 was positively correlated with WZ3105 and MPS-1-IN-1 in the cancer therapeutics response portal database. Conclusion: We built and verified a risk model for HNSCC prognosis using seven pyroptosis-related signature genes, which could predict the overall survival of HNSCC patients and facilitate treatment. [ABSTRACT FROM AUTHOR]

The understanding of people's inter-regional mobility behaviors, such as predicting the next activity region (AR) or uncovering the intentions for regional mobility, is of great value to public administration or business interests. While there are numerous studies on human mobility, these studies are mainly from a statistical view or study movement behaviors within a region. The work on individual-level inter-regional mobility behavior is limited. To this end, in this article, we propose a dynamic region-relation-aware graph neural network (DRRGNN) for exploring individual mobility behaviors over ARs. Specifically, we aim at developing models that can answer three questions: (1)Which regions are the ARs? (2)Which region will be the next AR, and (3) Why do people make this regional mobility? To achieve these tasks, we first propose a method to find out people's ARs. Then, the designed model integrates a dynamic graph convolution network (DGCN) and a recurrent neural network (RNN) to depict the evolution of relations between ARs and mine the regional mobility patterns. In the learning process, the model further considers peoples' profiles and visited point-of-interest (POIs). Finally, extensive experiments on two real-world datasets show that the proposed model can significantly improve accuracy for both the next AR prediction and mobility intention prediction. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumors with a poor prognosis. Type X collagen a 1 chain (COL10A1), a member of the collagen family, is a gene associated with the progression of a variety of human tumors, but the specific function and molecular mechanism of COL10A1 in pancreatic cancer remain unclear. Our study found that COL10A1 is highly expressed in pancreatic cancer cells and tissues, and its high expression is related to poor prognosis and some clinicopathological features, such as tumor size and differentiation. Biological functional experiments showed that overexpression of COL10A1 enhanced the proliferation and migration of PDAC cells. Interestingly, discoid protein domain receptor 2 (DDR2), the receptor of COL10A1, is regulated by COL10A1. We found that the COL10A1-DDR2 axis activates the mitogenactivated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, which leads to epithelial-mesenchymal transformation (EMT) and accelerates the progression of pancreatic cancer. In summary, COL10A1 regulates PDAC cell proliferation and MEK/ERK signaling pathways by binding to DDR2 to promote migration, invasion and EMT. Our study suggested that COL10A1 might be a critical factor in promoting PDAC progression. More research is needed to confirm COL10A1 as a potential biomarker and therapeutic target for PDAC. [ABSTRACT FROM AUTHOR]

Copper toxicity involves the destruction of mitochondrial metabolic enzymes, triggering an unusual mechanism of cell death called cuproptosis, which proposes a novel approach using copper toxicity to treat cancer. However, the biological function of cuproptosis has not been fully elucidated in kidney renal clear cell carcinoma (KIRC). Using the expression profile of 13 cuproptosis regulators, we first identified two molecular subtypes related to cuproptosis defined as “hot tumor” and “cold tumor”, having different levels of biological function, clinical prognosis, and immune cell infiltration. We obtained three gene clusters using the differentially expressed genes between the two cuproptosisrelated subtypes, which were associated with different molecular activities and clinical characteristics. Next, we developed and validated a cuproptosis prognostic model that included two genes (FDX1 and DBT). The calculated risk score could divide patients into high- and low-risk groups. The high-risk group had a poorer prognosis, lower level of immune infiltration, higher frequency of gene alterations, and greater levels of FDX1 methylation and limited DBT methylation. The risk score was also an independent predictive factor for overall survival in KIRC. The established nomogram calculating the risk score achieved a high predictive ability for the prognosis of individual patients (area under the curve: 0.860). We then identified small molecular inhibitors as potential treatments and analyzed the sensitivity to chemotherapy of the signature genes. Tumor immune dysfunction and exclusion (TIDE) showed that the high-risk group had a higher level of TIDE, exclusion and dysfunction that was lower than the lowrisk group, while the microsatellite instability of the high-risk group was significantly lower. The results of two independent immunotherapy datasets indicated that cuproptosis regulators could influence the response and efficacy of immunotherapy in KIRC. Our study provides new insights for individualized and comprehensive therapy of KIRC. [ABSTRACT FROM AUTHOR]

Water shortage is a key factor that can restrict peach tree growth. Plants produce fatty acids and the fatty acid derivatives lauric acid (LA) and 12-hydroxylauric acid (LA-OH), which are involved in abiotic stress responses, but the underlying stress response mechanisms remain unclear. In this study, physiological examination revealed that in Prunus persica (L.) Batsch, pretreatment with 50 ppm LA-OH and LA reduced drought stress, efficiently maintained the leaf relative water content, and controlled the relative conductivity increase. Under drought stress, LA-OH and LA treatments prevented the degradation of photosynthetic pigments, increased the degree of leaf stomatal opening and enhanced the net photosynthetic rate. Compared with drought stress, LA-OH and LA treatment effectively increased the net photosynthetic rate by 204.55% and 115.91%, respectively, while increasing the Fv/Fm by 2.75% and 7.75%, respectively, but NPQ decreased by 7.67% and 37.54%, respectively. In addition, the level of reactive oxygen species increased under drought stress. The content of O2 - in LA-OH and LA treatment decreased by 12.91% and 11.24% compared to CK-D, respectively, and the content of H2O2 decreased by 13.73% and 19.94%, respectively. At the same time, the content of malondialdehyde (MDA) decreased by 55.56% and 58.48%, respectively. We believe that the main reason is that LA-OH and LA treatment have improved the activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). The application of exogenous LA increased the levels of soluble sugars, soluble proteins, proline and free amino acids under drought stress, and maintained the osmotic balance of cells. Compared with CK-D treatment, it increased by 24.11%, 16.89%, 29.3% and 15.04%, respectively. At the same time, the application of exogenous LA-OH also obtained similar results. In conclusion, exogenous LA-OH and LA can alleviate the damage to peach seedlings caused by drought stress by enhancing the photosynthetic and antioxidant capacities, increasing the activities of protective enzymes and regulating the contents of osmotic regulators, but the molecular mechanism is still in need of further exploration. [ABSTRACT FROM AUTHOR]

Sepsis-induced myocardial dysfunction (SIMD) is a fatal disease with no specific treatment worldwide to this day. As a biological product, platelet-rich plasma (PRP) has attracted much attention due to its diverse and potential biological effects. However, its role in lipopolysaccharide (LPS)-induced cardiac injury has not been fully investigated. This study aimed to explore the mechanism of PRP in SIMD. PRP (30 µL) was injected in situ into the heart, and LPS (10 mg/kg) was injected intraperitoneally into mice. Neonatal rat cardiomyocytes were treated with LPS (1 μg/ml) for 24 h. The results showed that, compared with the LPS group, PRP significantly decreased the levels of Lactate dehydrogenase (LDH) and Creatine Kinase MB (CK-MB), and improved cardiac function. In addition, PRP markedly decreased the Malonic dialdehyde (MDA) content, and increased the Superoxide dismutase (SOD) activity and Glutathione (GSH) level, demonstrating that PRP alleviated LPS-induced oxidative stress. The Western blot and qPCR results showed that LPS-induced ferroptosis and inflammation effects in vivo and in vitro were ameliorated after PRP treatment. Moreover, PRP can alleviate erastin-induced ferroptosis and improve cell viability. Mechanistically, p-AKT and p-mTOR expressions were down-regulated after treatment with LPS, while PRP pretreatment could reverse this effect. In summary, our study demonstrated that PRP could play a unique role in reducing LPS-induced cardiac injury through regulation of AKT/mTOR signaling pathways. These findings provide a new therapeutic direction for treating SIMD. [ABSTRACT FROM AUTHOR]