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Mian Zeng, Qingui Chen, Wenjie Liang, Wanmei He, Haichong Zheng, Chunrong Huang Department of Medical Intensive Care Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Background: Impaired renal function is often neglected in COPD patients. Considering that COPD patients usually have an ongoing prothrombotic state and systemic inflammation status, we investigated the association among them and explored the predictive value of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), on concealed chronic renal failure (CRF) in COPD patients.Methods: COPD patients were recruited from the First Affiliated Hospital of Sun Yat-Sen University between January 2015 and December 2016. Control was selected from contemporaneous hospitalized patients without COPD and matched by age and gender at a ratio of 1:1. Estimated glomerular filtration rate (eGFR) was calculated by using the Chronic Kidney Disease Epidemiology Collaboration formula, and all subjects were categorized as having normal renal function (eGFR ≥60 mL min–1 1.73 m–2) and having concealed CRF (normal serum creatinine while eGFR

This report is on a 22-year-old male vegetarian with acute polyneuropathy secondary to vitamin B(12) deficiency. He presented with weakness and numbness of the distal limbs and absent deep tendon reflex in all four extremities. Nerve conduction study (NCS) showed an axonal type sensori-motor polyneuropathy. Serum biochemical studies revealed vitamin B(12) level of 119 pg/mL (reference range 185-710 pg/mL), with elevated creatine kinase (CK) (719 U/L) and homocysteine (Hcy) (24.04 μmol/L) levels. Anti-parietal cell antibody test was positive. The patient received both oral and intramuscular injection of vitamin B(12). The amplitude of the median and ulnar motor NCS increased 2.5 months later, while muscle power of the ankle plantar flexion and dorsiflexion recovered after 3.5 and 5.5 months, respectively. Follow-up NCS after 14.5 months showed response in sural NCS, but not the peroneal NCS. Follow-up also showed decreased serum Hcy and CK to 9.6 μmol/L and 198 U/L, respectively, and increasing amplitude of response. Recovery sequence involved muscle power of the proximal muscles, hands, plantar flexion, and dorsiflexion of the feet, and followed by sensory conduction. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The prevalence of dementia is expected to increase in Chinese society in the next 40 years. Family members remain the primary caregivers and bear a heavy burden. The present study aims to examine the reliability and validity of the Chinese version of the Zarit Burden Interview (CZBI). METHOD: One hundred eighty-one patient-caregiver dyads were recruited. Caregivers completed the measures of the CZBI, Caregiver Activity Survey (CAS) and 12-item Chinese Health Questionnaire (CHQ-12). Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess the patients' condition. RESULTS: Overall reliability of CZBI was good, with the internal consistency and test-retest reliability being high. The CZBI was highly correlated with the scores of the CAS and CHQ-12, which provides evidence of concurrent validity. Factor analysis found five factors, which accounted for 60% of variance. CONCLUSION: The CZBI is feasible for measuring feelings of burden of caregivers for Taiwanese patients with dementia. [ABSTRACT FROM AUTHOR]

Background: We investigated whether shock wave (SW)-pretreated autologous adipocyte-derived mesenchymal stem cells (ADMSCs) seeded in the cell-sheet scaffold (CSS) could inhibit left ventricular (LV) remodeling and improve LV ejection fraction (LVEF) in old myocardial infarction (MI)., Methods: Mini-pigs (n=20) were divided into group 1 (sham-operated control), group 2 (old MI), group 3 (old MI + autologous ADMSCs/1.0×107 in CSS on LV myocardium), and group 4 [old MI + SW (0.12 mJ/mm2 for total 140 shots)-pretreated ADMSCs in CSS on LV myocardium]. Treatments started on day 28 after MI induction. In vivo and in vitro studies were conducted., Results: Cell viability/relative mitochondria DNA expression/mitochondrial cytochrome C/adenosine triphosphate concentration in ADMCSs and protein expressions of angiogenesis factors (vascular endothelial growth factor [VEGF]/stromal cell-derived factor-1 [SDF-1])/mitochondrial respiratory chain complexes I-IV/oxygen consumption rate were higher in group 4 than in group 3 (P<0.001). By day 180, LVEF and small vessel numbers in the peri-infarct or infarct area were highest in group 1, lowest in group 2, and significantly lower in group 3 than in group 4. In contrast, the LV dimension was opposite to the pattern of change in LVEF in all groups (P<0.0001). The basal/middle/apical infarct and fibrotic areas were inversely related to LVEF in all groups (all P<0.0001). Protein levels of angiogenetic markers (SDF-1α/C-X-C chemokine receptor type 4/VEGF/angiopoietin-1) were significantly and persistently increased from groups 1 to 4. In contrast, protein levels of endothelial-cell markers (von Willebrand factor or endothelial nitric oxide synthase) showed an identical pattern to LVEF in all groups (all P<0.0001)., Conclusion: SW pretreatment of ADMSCs seeded in CSS offered significant benefits in preserving LV performance and ameliorating LV remodeling in mini-pigs with old MI., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study tested the hypothesis that combined ceftriaxone (Cef) and human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) was better than either therapy for alleviating acute septic arthritis (ASA)., Methods and Results: Adult-male C57BL/6 mice were categorized into control group (Clt), group A (ASA only), group B [ASA + Cef (5 mg/kg, IM per day, at days 2 to 16 after ASA induction)], group C [ASA + HUCDMSCs (5 × 105 per mice at days 2, 3, 4 after ASA induction)], and group D (ASA + Cef + HUCDMSCs). Animals were euthanized by day 28. The result demonstrated that the body weight was significantly lower, whereas the ratio of kidney or spleen weight to WB, circulatory WBC count, bacterial colony-formation-unit from circulatory/kidney extraction were significantly higher in group A than in other groups (all P < .001). The proinflammatory cytokines (IL-6/TNF-α) of knee joint fluid were lowest in Clt and significantly and progressively reduced from groups A to D, whereas the circulatory levels of these 2 parameters at the time points of days 3/7/28 exhibited an identical pattern as knee joint fluid among the groups (all P-value < .0001). The scores of vertebral-bone destructions/inflamed synovium were lowest in Clt, highest in group A, significantly higher in group C than in groups B/D, and significantly higher in group C than in group D (all P < .0001)., Conclusion: Combined antibiotics and Cef and HUCDMSCs was superior to just one therapy for suppressing circulatory and tissue levels of inflammation and knee joint destruction in ASA., (© The Author(s) 2024. Published by Oxford University Press.)

The NLRP3 inflammasome is an essential component of the innate immune system, but excessive activation can lead to inflammatory diseases. Ion fluxes across the plasma membrane or from intracellular stores are known to regulate NLRP3 inflammasome activation. Deep-sea water (DSW) contains high concentrations of many mineral ions, which could potentially influence NLRP3 inflammasome activation. However, the impact of DSW on NLRP3 inflammasome activation has not been investigated. Here, we demonstrated that DSW with water hardness levels up to 500 mg/L did not affect cell viability or the expression of NLRP3 inflammasome components in macrophages derived from THP-1 cells. However, the DSW significantly inhibited IL-1β secretion and caspase-1 activation in response to NLRP3 activators such as nigericin, ATP, or monosodium urate (MSU) crystals. Mechanically, it was discovered that the presence of 5 mM magnesium ions (Mg2 + ), equivalent to the Mg2 + concentration found in the DSW with a water hardness of 500 mg/L, inhibits NLRP3 inflammasome activation. This indicates that Mg2 + contributes to the mechanism by which DSW mitigates NLRP3 inflammasome activation. Moreover, DSW administration effectively lessens MSU-triggered peritonitis in mice, a commonly used model for examining the impacts of NLRP3 inflammasome activation. These results show that DSW enriched with Mg 2+ could potentially be beneficial in modulating NLRP3 inflammasome-associated diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Aim: To investigate the metabolism and disposition characteristics of HSK7653 in healthy male Chinese participants., Methods: A single oral dose of 80 μCi (25 mg) [ 14 C]HSK7653 capsules was administered to six healthy participants, and blood, plasma, urine and faeces were collected. Quantitative and qualitative analysis was conducted to investigate the pharmacokinetics, blood-to-plasma ratio, mass balance and metabolism of HSK7653., Results: The drug was well absorbed and reached a maximum concentration at 1.25 h. The drug-related components (HSK7653 and its metabolites) were eliminated slowly, with a half-life (t 1/2 ) of 111 h. Unchanged HSK7653 contributed to more than 97% of the total radioactivity in all plasma samples. The blood-to-plasma ratio (0.573-0.845) indicated that HSK7653 did not tend to distribute into blood cells. At 504 h postdose, up to 95.9% of the dose was excreted, including 79.8% in urine and 16.1% in faeces. Most of the radioactivity (75.5% dose) in excreta was unchanged HSK7653. In addition, nine metabolites were detected in urine and faeces. The most abundant metabolite was M6-2, a dioxidation product of HSK7653, which accounted for 4.73% and 2.63% of the dose in urine and faeces, respectively. The main metabolic pathways of HSK7653 in vivo included oxidation, pyrrole ring opening and sulphonamide hydrolysation., Conclusion: HSK7653 was well absorbed, slightly metabolized and slowly excreted in humans. The high plasma exposure and long t 1/2 of HSK7653 may contribute to its long-lasting efficacy as a long-acting dipeptidyl peptidase-4 inhibitor., (© 2024 John Wiley & Sons Ltd.)

Hepatocellular carcinoma (HCC) is a malignant tumor with extremely high mortality. The tumor microenvironment is the "soil" of its occurrence and development, and the inflammatory microenvironment is an important part of the "soil". Bile acid is closely related to the occurrence of HCC. Bile acid metabolism disorder is not only directly involved in the occurrence and development of HCC but also affects the inflammatory microenvironment of HCC. Yinchenhao decoction, a traditional Chinese medicine formula, can regulate bile acid metabolism and may affect the inflammatory microenvironment of HCC. To determine the effect of Yinchenhao decoction on bile acid metabolism in mice with HCC and to explore the possible mechanism by which Yinchenhao decoction improves the inflammatory microenvironment of HCC by regulating bile acid metabolism, we established mice model of orthotopic transplantation of hepatocellular carcinoma. These mice were treated with three doses of Yinchenhao decoction, then liver samples were collected and tested. Yinchenhao decoction can regulate the disorder of bile acid metabolism in liver cancer mice. Besides, it can improve inflammatory reactions, reduce hepatocyte degeneration and necrosis, and even reduce liver weight and the liver index. Taurochenodeoxycholic acid, hyodeoxycholic acid, and taurohyodeoxycholic acid are important molecules in the regulation of the liver inflammatory microenvironment, laying a foundation for the regulation of the liver tumor inflammatory microenvironment based on bile acids. Yinchenhao decoction may improve the inflammatory microenvironment of mice with HCC by ameliorating hepatic bile acid metabolism., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

The accurate diagnosis and staging of lymph node metastasis (LNM) are crucial for determining the optimal treatment strategy for head and neck cancer patients. We aimed to develop a 3D Resnet model and investigate its prediction value in detecting LNM. This study enrolled 156 head and neck cancer patients and analyzed 342 lymph nodes segmented from surgical pathologic reports. The patients' clinical and pathological data related to the primary tumor site and clinical and pathology T and N stages were collected. To predict LNM, we developed a dual-pathway 3D Resnet model incorporating two Resnet models with different depths to extract features from the input data. To assess the model's performance, we compared its predictions with those of radiologists in a test dataset comprising 38 patients. The study found that the dimensions and volume of LNM + were significantly larger than those of LNM-. Specifically, the Y and Z dimensions showed the highest sensitivity of 84.6% and specificity of 72.2%, respectively, in predicting LNM + . The analysis of various variations of the proposed 3D Resnet model demonstrated that Dual-3D-Resnet models with a depth of 34 achieved the highest AUC values of 0.9294. In the validation test of 38 patients and 86 lymph nodes dataset, the 3D Resnet model outperformed both physical examination and radiologists in terms of sensitivity (80.8% compared to 50.0% and 91.7%, respectively), specificity(90.0% compared to 88.5% and 65.4%, respectively), and positive predictive value (77.8% compared to 66.7% and 55.0%, respectively) in detecting individual LNM + . These results suggest that the 3D Resnet model can be valuable for accurately identifying LNM + in head and neck cancer patients. A prospective trial is needed to evaluate further the role of the 3D Resnet model in determining LNM + in head and neck cancer patients and its impact on treatment strategies and patient outcomes., (© 2024. The Author(s).)

Clostridioides difficile is a Gram-positive, anaerobic, and spore-forming bacterial member of the human gut microbiome. The primary virulence factors of C. difficile are toxin A and toxin B. These toxins damage the cell cytoskeleton and cause various diseases, from diarrhea to severe pseudomembranous colitis. Evidence suggests that bacteriophages can regulate the expression of the pathogenicity locus (PaLoc) genes of C. difficile. We previously demonstrated that the genome of the C. difficile RT027 strain NCKUH-21 contains a prophage-like DNA sequence, which was found to be markedly similar to that of the φCD38-2 phage. In the present study, we investigated the mechanisms underlying the φNCKUH-21-mediated regulation of the pathogenicity and the PaLoc genes expression in the lysogenized C. difficile strain R20291. The carriage of φNCKUH-21 in R20291 cells substantially enhanced toxin production, bacterial motility, biofilm formation, and spore germination in vitro. Subsequent mouse studies revealed that the lysogenized R20291 strain caused a more severe infection than the wild-type strain. We screened three φNCKUH-21 genes encoding DNA-binding proteins to check their effects on PaLoc genes expression. The overexpression of NCKUH-21&#95;03890, annotated as a transcriptional regulator (phage transcriptional regulator X, PtrX), considerably enhanced toxin production, biofilm formation, and bacterial motility of R20291. Transcriptome analysis further confirmed that the overexpression of ptrX led to the upregulation of the expression of toxin genes, flagellar genes, and csrA. In the ptrX-overexpressing R20291 strain, PtrX influenced the expression of flagellar genes and the sigma factor gene sigD, possibly through an increased flagellar phase ON configuration ratio., Competing Interests: Declaration of Interest Statement The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The underlying mechanism of colorectal cells developing into cancer cells has been extensively investigated, yet is still not fully delineated, resulting in the treatment of advanced colorectal cancer (CRC) remains regrettably an unmet need. Zinc Finger Protein 746/Parkin-interacting substrate (ZNF746/PARIS) has previously been identified to play a fundamental role on bladder cancer cell proliferation and metastasis that were effectively inhibited by melatonin (Mel). In this study, we utilized ex vivo/in vivo studies to verify whether the ZNF746 signaling was also crucial in CRC growth/invasion/migration. Tissue-bank specimens showed that the protein expression of ZNF746 was significantly increased in CRC than that of healthy colorectal tissues (p < 0.001). Additionally, in vitro study demonstrated that excessive expression of ZNF746 significantly inhibited mitochondrial activity via (1) interfering with the dynamic balance of mitochondrial fusion/fission and (2) inhibiting the protein expression of MFN1/MFN2/PGC1a (all p < 0.001). Furthermore, we identified that inhibition of ZNF746 protein expression significantly reduced the resistance of CRC cell lines to the anticancer drug of 5-FU (p < 0.001), whereas overexpression of ZNF746 significantly augmented resistance of CRC cells to 5-FU (all p < 0.001). Finally, using the cell culture method, we found that combined Mel and 5-FU was superior to merely one on promoting the CRC cell apoptosis (p < 0.001). Our results confirmed that ZNF746 signaling played a cardinal role of CRC cell proliferation/survival and combined Mel and 5-FU treatment attenuated the resistance of CRC cells to the drug mainly through suppressing this signaling., (© 2023 Wiley Periodicals LLC.)

Improper use of antibiotics has led to the global rise of drug-resistant biofilm bacteria. Thus, researchers have been increasingly interested in green materials that are highly biocompatible and have low toxicity. Here, nanogels (NGs) with imine bonds were synthesized by crosslinking kiwifruit-derived DNA's primary amine and aromatic aldehydes (cuminaldehyde, p-anisaldehyde, or vanillin) under water-in-hexane emulsion processes. Transmission electron microscope showed that the NGs had spherical geometry with an average particle size ranging from 40 to 140 nm and that the zeta potential indicated a negative charge. Additionally, the DNA-aromatic aldehyde NGs showed low cytotoxicity toward normal cell organoids and human RBCs in cell viability tests. These NGs were also tested against four pathogenic bacteria for various assays. DNA-vanillin (DNA-VA) NGs exhibited significant antibacterial effects against bacteria with very low inhibitory concentrations as seen in a minimum inhibitory concentration assay. Scanning electron microscope observation revealed that the bacteria were deformed, and immunoblotting detected intracellular groEL protein expression. In agreement with these results, DNA-aromatic aldehyde NGs successfully protected C. elegans from P. aeruginosa-induced lethality. These DNA NGs provided a multivalent 3D space for antibacterial aromatic aldehydes to tether, enhancing their interaction with the bacterial wall. These results offer a new direction for the development of novel antibiotics in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Thermally triggered spatial symmetry breaking in traditional ferroelectrics has been extensively studied for manipulation of the ferroelectricity. However, photoinduced molecular orbital breaking, which is promising for optical control of ferroelectric polarization, has been rarely explored. Herein, for the first time, we synthesized a homochiral fulgide organic ferroelectric crystal (E)-(R)-3-methyl-3-cyclohexylidene-4-(diphenylmethylene)dihydro-2,5-furandione (1), which exhibits both ferroelectricity and photoisomerization. Significantly, 1 shows a photoinduced reversible change in its molecular orbitals from the 3 π molecular orbitals in the open-ring isomer to 2 π and 1 σ molecular orbitals in the closed-ring isomer, which enables reversible ferroelectric domain switching by optical manipulation. To our knowledge, this is the first report revealing the manipulation of ferroelectric polarization in homochiral ferroelectric crystal by photoinduced breaking of molecular orbitals. This finding sheds light on the exploration of molecular orbital breaking in ferroelectrics for optical manipulation of ferroelectricity., (© 2023 Wiley-VCH GmbH.)

Objective: This study aimed to assess the safety and efficacy of triple-dose intravenous tranexamic acid (TXA) in patients following total hip arthroplasty (THA) using thromboelastography (TEG)., Methods: One hundred thirty patients undergoing THA were prospectively enrolled in the study. According to the intravenous infusion TXA dose, patients were divided into single-dose (n=65; mean age=60.8 ± 8.1 years) and triple-dose groups (n=65; mean age=61.8 ± 8.6 years). Complete blood count (CBC), conventional coagulation tests (CCT), and TEG were conducted 1 day before the operation, on postoperative day 1 (POD1), and postoperative day 7 (POD7). Color Doppler ultrasonography was performed 1 day before the operation and on POD7. Drainage blood loss, total blood loss (TBL), hidden blood loss (HBL), deep vein thrombosis (DVT) incidence, and blood transfusion rates were calculated and recorded. The CCT, CBC, and TEG parameters were compared between the 2 groups., Results: Single- and triple-dose groups had significantly different hematocrit on POD7 (P < .05). No significant differences were found in CCT and hemoglobin at any corresponding time point between the 2 groups (P > .05). Despite the reaction time (R) on POD1 (P < .05), there were no significant differences in other TEG parameters at any other time point between the 2 groups (P > 0.05). For drainage blood loss and TBL, the triple-dose group had lesser blood loss than the single-dose group (P < .05). However, no significant differences were found for blood transfusion rate, HBL, or incidence of DVT (P > .05)., Conclusion: Compared with single-dose, triple-dose TXA can be more effective in decreasing blood loss without increasing DVT incidence in patients undergoing THA. Although there is a notable disparity in the R time on POD1, the administration of triple-dose TXA does not substantially impact the coagulation status as assessed by TEG and CCT.

Background: We examined the impact of adipose-derived mesenchymal stem cell (ADMSC)-facilitated empagliflozin (EMPA) therapy for alleviating hyperglycemic induced neuropathy [i.e., diabetic neuropathy (DN)]., Methods: Study constituted N2a cell culture and rats to be classified into groups 1 (sham-operated-control)/2 (DN)/3 (DN + empagliflozin/20 mg/kg/daily orally for 6 weeks since post-day-7 DN induction)/4 (DN + ADMSCs/1.2 × 10 6 cells by vein transfusion at time intervals of 1/3/5 weeks after DN induction)/5 (DN + empagliflozin + ADMSCs) and sacrificed by day-42 after DN induction., Results: In vitro results showed that, compared to N2a cells, the cellular levels of senescence/DNA-damage and protein expressions of oxidative-stress (OS), apoptotic, autophagic and inflammatory biomarkers were significantly higher in N2a + glucose (25 mM) but were significantly reversed in N2a + glucose + ADMSCs, whereas the cellular levels of mitochondrial cytochrome C and protein levels of anti-oxidants displayed an opposite pattern of OS (all P<0.001). The above-mentioned parameters (i.e., OS/apoptosis/fibrosis/autophagy/DNA-damage) were lowest in N2a cells, highest in N2a + glucose and significantly higher in N2a + glucose + EMPA (50 μM) than in N2a + glucose + EMPA (150 μM) (all P<0.001). By days 7/14/21/28/35/42 after DN induction, the values of thermal paw-withdrawal-latency (TPWL)/mechanical-paw-withdrawal-threshold were highest in group 1 and significantly progressively increased from groups 2/4/3/5 (all P<0.0001). The cellular levels of unmyelinated C- and myelinated A-δ fibers, and protein levels of OS/apoptotic/DNA-damaged/fibrotic/autophagic/inflammatory/pain-facilitated/voltage-gated sodium channel biomarkers in L4-L5 levels of dorsal-root-ganglia exhibited an contradictory manner of TPWL among the groups (all P<0.0001)., Conclusions: Combination of EMPA and ADMSC therapy was superior to either alone for improving outcomes of DN., Competing Interests: None., (AJTR Copyright © 2023.)

Histopathological images provide the medical evidences to help the disease diagnosis. However, pathologists are not always available or are overloaded by work. Moreover, the variations of pathological images with respect to different organs, cell sizes and magnification factors lead to the difficulty of developing a general method to solve the histopathological image classification problems. To address these issues, we propose a novel cross-scale fusion (CSF) transformer which consists of the multiple field-of-view patch embedding module, the transformer encoders and the cross-fusion modules. Based on the proposed modules, the CSF transformer can effectively integrate patch embeddings of different field-of-views to learn cross-scale contextual correlations, which represent tissues and cells of different sizes and magnification factors, with less memory usage and computation compared with the state-of-the-art transformers. To verify the generalization ability of the CSF transformer, experiments are performed on four public datasets of different organs and magnification factors. The CSF transformer outperforms the state-of-the-art task specific methods, convolutional neural network-based methods and transformer-based methods. The source code will be available in our GitHub https://github.com/nchucvml/CSFT.

Biofilm-forming bacteria E. coli and P. aeruginosa have both exhibited resistance against multiple antibiotics in clinical settings. To find a solution, researchers have turned to antibacterial structurally modified from natural materials that are harmless to the human body. Among these is DNA, a natural polymer composed of deoxyribose that when treated with HCl exposes its aldehyde groups and produces DNA-HCl. Here, we crosslinked these aldehyde groups with the primary amines in S-benzyl-L-cysteine (SBLC) using a Schiff reaction to obtain DNA-HCl-SBLC. We additionally treated alginate acid (AA) with EDAC, obtaining AA-EDAC, and substituting it with SBLC to produce AA-SBLC. We incorporated the above reactions with an emulsification process to produce nanogels (NGs) that were verified to be spherical and possessing benzene rings successfully grafted onto DNA-HCl and AA-EDAC. These natural NGs were proven to be negatively charged through zeta potential analysis and presented low cytotoxicity toward normal cells in cell organoid viability assays. These SBLC-modified polymers provided better inhibition of bacterial growth than those without modification. Moreover, after incubation with SBLC-modified NGs, bacteria expressed intracellular recA or pvdA in a dose-dependent manner, which was consistent with SEM data from damaged bacteria. Out of four tested NGs, DNA-HCl-SBLC NGs suppressed P. aeruginosa-induced sepsis most effectively and extended the lifespan of C. elegans. This study provides an alternative clinical solution to antibiotics-resistant biofilm strains., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Little research has explored galactagogue food consumption in China. This study aims to investigate consumption patterns and how they relate to perceived insufficient milk supply and exclusive breastfeeding., Methods: Data were collected from postpartum women in China at six time points: baseline demographic questionnaire before hospital discharge (T0), galactagogue food questionnaire at 1 month postpartum (T1), Hill and Humenick Lactation Scale at 6 weeks postpartum (T2), and breastfeeding practices at 1, 2, 3 and 4 months postpartum (T1, T3, T4, T5)., Results: Of 218 participants who completed the galactagogue food questionnaire, 64.68% were consumers. No association was found between galactagogue food consumption and perceived insufficient milk supply. Consumers were less likely to breastfeed exclusively., Discussion: Future research should emphasize a deeper understanding of consumer behaviors and family support in providing professional guidance on postpartum nutrition that considers not only social and cultural experiences but also broader medical aspects.

Background: The short form of the Borderline Symptom List (BSL-23) is a self-rated instrument developed from the initial 95-item German version of the Borderline Symptom List (BSL-95). It is widely used among Chinese adults, but its applicability, factor structure and validity remain uncertain in adolescents. This study aimed to evaluate the psychometric properties of the Chinese Mandarin version of the BSL-23 in a sample of suicidal adolescents., Methods: The Chinese Mandarin BSL-23 was given to 279 outpatient adolescents with self-injurious thoughts or behaviors. The factor structure, reliability, convergent validity, criterion-related validity and cut-off value were investigated., Results: The Chinese Mandarin version of the BSL-23 demonstrated a one-factor structure and replicated the original version. The scale had high reliability and good test-retest stability. The Chinese Mandarin BSL-23 was correlated with depression, hopelessness, impulsivity, emotional dysregulation, self-esteem, loneliness, childhood trauma and parental bonding patterns evaluated with a variety of scales. The measure showed good criterion-related validity and predictive accuracy (AUC = 0.87) for self-injurious and suicidal adolescents with borderline personality disorder (BPD) at a cut-off point of 60/61 (mean score 2.60/2.65), with a sensitivity of 0.76 and specificity of 0.83., Conclusions: The Chinese Mandarin version of the BSL-23 is a reliable and valid self-reported instrument to assess BPD symptomatology among suicidal adolescents., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Psoroptes mites are the common ecto-parasites of wild and domestic animals worldwide, which causes considerable economic losses in livestock industry. Microscopy is deemed to be the 'gold standard' for the diagnosis of Psoroptes mite infection but it has poor sensitivity for low mite infections and/or sub-clinical infections. To overcome these shortcomings, we screened four genes to develop a sensitive and specific PCR for the detection of Psoroptes mite infection in rabbits, and confirmed its practicability in detecting early infection and monitoring treatment outcome with traditional microscopy and serological tests. Results showed that PCR assay targeting ITS2 (ITS2-PCR) had a high specificity and sensitivity (detection limit: 40.3 pg/μL DNA) for detecting P. ovis DNA. In rabbits artificially infected with P. ovis, all three diagnostic tests showed the same detection rate from 14 days post infection (dpi) to 42 days dpi. However, these diagnostic tests behave differently at 7 dpi and after treatment: at 7 dpi, the detection rate of ITS2-PCR was higher than rPsoSP3-based iELISA and traditional microscopy (ITS2-PCR: 88.9%, rPsoSP3-iELISA: 77.7%, microscopy: 33.3%); at 7 days post treatment (dpt), positivity rates of ITS2-PCR and microscopy rapidly decreased to 0.00% and 11.1%, whereas rPsoSP3-iELISA remained 100% positive rate. Furthermore, the comprehensive comparisons of diagnostic performance and features of three diagnostic tests at 7 dpi were performed. Compared to ITS2-PCR or rPsoSP3-iELISA, microscopy had the lowest sensitivity, and the agreement between these assays was low (κ < 0.3). Field study showed that ITS2-PCR showed a higher detection rate than microscopy (19.4% and 11.1%, respectively). Our results suggested that the ITS2-PCR developed in this study provided a new laboratory tool for diagnosis of P. ovis var. cuniculi infection, and it had advantages over microscopic examination in detection low-level mite infections and serological assay in monitoring treatment outcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: To estimate the incidence and identify risk factors of postpartum hemorrhage (PPH) after vaginal delivery., Methods: A systematic review and meta-analysis was conducted. PubMed, Cochrane Library, CINAHL, Web of Science, EMBASE, and ClinicalTrials.gov databases were systematically searched from inception to April 30th, 2022. Cross-sectional, cohort, case-control, and secondary analysis of randomized controlled studies that reported the incidence of PPH and the related risk factors in vaginal delivery were eligible through screening of 2343 articles. The incidence, associated standard error, adjusted odds ratios, relative risks and associated 95% confidence intervals were combined in the meta-analysis., Results: Thirty-six articles were included in the descriptive review. The incidence of PPH (blood loss ≥500 mL and blood loss ≥1000 mL) was 17% and 6%, respectively. Forty-one identified risk factors were divided into five categories under two criteria: history and demographics; maternal comorbidity; pregnancy-related factors; labor-related factors; delivery-related factors., Conclusions: With the increasing incidence of PPH globally, obstetric health care providers need to improve their awareness of these multi-factorial risks to optimize obstetric care and reduce maternal morbidity. This systematic review and meta-analysis have raised important questions about the nature of vaginal delivery, such as the duration of prolonged labor, details on the use of oxytocin, and the presence of genital tract trauma. There should be highlighted by obstetric personnel on these factors during a patients' labor process., (© 2023 Japan Society of Obstetrics and Gynecology.)

Objective: Common bile duct (CBD) stones caused diseases are life-threatening. Because CBD stones locate in the distal part of the CBD and have relatively small sizes, detecting CBD stones from CT scans is a challenging issue in the medical domain., Methods and Procedures: We propose a deep learning based weakly-supervised method called multiple field-of-view based attention driven network (MFADNet) to detect CBD stones from CT scans based on image-level labels. Three dominant modules including a multiple field-of-view encoder, an attention driven decoder and a classification network are collaborated in the network. The encoder learns the feature of multi-scale contextual information while the decoder with the classification network is applied to locate the CBD stones based on spatial-channel attentions. To drive the learning of the whole network in a weakly-supervised and end-to-end trainable manner, four losses including the foreground loss, background loss, consistency loss and classification loss are proposed., Results: Compared with state-of-the-art weakly-supervised methods in the experiments, the proposed method can accurately classify and locate CBD stones based on the quantitative and qualitative results., Conclusion: We propose a novel multiple field-of-view based attention driven network for a new medical application of CBD stone detection from CT scans while only image-levels are required to reduce the burdens of labeling and help physicians automatically diagnose CBD stones. The source code is available at https://github.com/nchucvml/MFADNet after acceptance., Clinical Impact: Our deep learning method can help physicians localize relatively small CBD stones for effectively diagnosing CBD stone caused diseases., (This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.)

Goal: Diagnosing the corpus-predominant gastritis index (CGI) which is an early precancerous lesion in the stomach has been shown its effectiveness in identifying high gastric cancer risk patients for preventive healthcare. However, invasive biopsies and time-consuming pathological analysis are required for the CGI diagnosis. Methods: We propose a novel gastric section correlation network (GSCNet) for the CGI diagnosis from endoscopic images of three dominant gastric sections, the antrum, body and cardia. The proposed network consists of two dominant modules including the scaling feature fusion module and section correlation module. The front one aims to extract scaling fusion features which can effectively represent the mucosa under variant viewing angles and scale changes for each gastric section. The latter one aims to apply the medical prior knowledge with three section correlation losses to model the correlations of different gastric sections for the CGI diagnosis. Results: The proposed method outperforms competing deep learning methods and achieves high testing accuracy, sensitivity, and specificity of 0.957, 0.938 and 0.962, respectively. Conclusions: The proposed method is the first method to identify high gastric cancer risk patients with CGI from endoscopic images without invasive biopsies and time-consuming pathological analysis., (© 2023 The Authors.)

Organic photochromic compounds have been widely investigated for optical memory storage and switches. Very recently, we pioneeringly discovered optical control of ferroelectric polarization switching in organic photochromic salicylaldehyde Schiff base and diarylethene derivatives, differently from the traditional ferroelectrics. However, the study of such intriguing photo-triggered ferroelectrics is still in its infancy and relatively scarce. In this manuscript, we synthesized a pair of new organic single-component fulgide isomers, ( E and Z )-3-(1-(4-( tert -butyl)phenyl)ethylidene)-4-(propan-2-ylidene)dihydrofuran-2,5-dione (1E and 1Z). They undergo prominent photochromism from yellow to red. Interestingly, only polar 1E has been proven to be ferroelectric, while the centrosymmetric 1Z does not meet the basic requirement for ferroelectricity. Besides, experimental evidence shows that the Z -form can be converted to the E -form by light irradiation. More importantly, the ferroelectric domains of 1E can be manipulated by light in the absence of an electric field, benefiting from the remarkable photoisomerization. 1E also adopts good fatigue resistance to the photocyclization reaction. As far as we know, this is the first example of organic fulgide ferroelectric reported with photo-triggered ferroelectric polarization response. This work has developed a new system for studying photo-triggered ferroelectrics and would also provide an expected perspective on developing ferroelectrics for optical applications in trap future., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Incidental thyroid abnormalities found on magnetic resonance imaging (MRI) of the neck are not uncommon. This study aimed to investigate the prevalence of incidental thyroid abnormalities in the cervical spine MRI of the degenerative cervical spondylosis (DCS) population indicated for surgery and to identify patients who require additional workup based on the recommendations of the American College of Radiology (ACR)., Methods: All consecutive patients with DCS and indications for cervical spine surgery from October 2014 to May 2019 in the Affiliated Hospital of Xuzhou Medical University were reviewed. All MRI scans of the cervical spine routinely include the thyroid. Cervical spine MRI scans were retrospectively evaluated for the prevalence, size, morphologic characteristics, and location of incidental thyroid abnormalities., Results: A total of 1,313 patients were included in the analysis, 98 (7.5%) of whom were found to have incidental thyroid abnormalities. The most frequent thyroid abnormality was thyroid nodules (5.3%), followed by goiters (1.4%). Other thyroid abnormalities included Hashimoto thyroiditis (0.4%) and thyroid cancer (0.5%). There was a statistically significant difference in age and sex between patients with DCS with and without incidental thyroid abnormalities (P=0.018 and P=0.007). Stratified by age, the results showed that the highest incidence of incidental thyroid abnormalities was found in patients aged 71 to 80 years (12.4%). Eighteen patients (1.4%) needed further ultrasound (US) and relevant workups., Conclusions: Incidental thyroid abnormalities are common in cervical MRI, with a prevalence of 7.5% identified in patients with DCS. Incidental thyroid abnormalities are large or have suspicious imaging features, and further evaluation with a dedicated thyroid US examination should be completed before cervical spine surgery is undertaken., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-484/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Chin-shin oolong tea is the most widely planted variety in Taiwan. This study fermented eight whole grains fermentation starter (EGS) with light (LOT), medium (MOT), and fully (FOT) oxidized Chin-shin oolong teas for ten weeks. Comparing the three fermentation beverages, it was found that LOT fermentation can obtain the highest catechins (1644.56 ± 60.15 ppm) among the functional and antioxidant components. MOT can obtain the highest glucuronic acid (19,040.29 ± 2903.91 ppm), tannins, total phenols, flavonoids, and angiotensin-converting enzyme (ACE) inhibitory activity. FOT can obtain the highest GABA (1360.92 ± 123.24 ppm). In addition, both the LOT and MOT showed a significant increase in their ability to scavenge DPPH radicals after fermentation. EGS fermented with lightly or moderately oxidized Chin-shin oolong tea may be considered a novel Kombucha.

This study tested the hypothesis that Jagged2/Notches promoted the endothelial-mesenchymal transition (endMT)-mediated pulmonary arterial hypertension (PAH) (i.e. induction by monocrotaline [MCT]/63 mg/kg/subcutaneous injection) through increasing the expression of GATA-binding factors which were inhibited by propylthiouracil (PTU) (i.e. 0.1% in water for daily drinking since Day 5 after PAH induction) in rodent. As compared with the control (i.e. HUVECs), the protein expressions of GATAs (3/4/6) and endMT markers (Snail/Zeb1/N-cadherin/vimentin/fibronectin/α-SMA/p-Smad2) were significantly reduced, whereas the endothelial-phenotype markers (CD31/E-cadherin) were significantly increased in silenced JAG2 gene or in silenced GATA3 gene of HUVECs (all p < 0.001). As compared with the control, the protein expressions of intercellular signallings (GATAs [3/4/6], Jagged1/2, notch1/2 and Snail/Zeb1/N-cadherin/vimentin/fibronectin/α-SMA/p-Smad2) were significantly upregulated in TGF-ß/monocrotaline-treated HUVECs that were significantly reversed by PTU treatment (all p < 0.001). By Day 42, the results of animal study demonstrated that the right-ventricular systolic-blood-pressure (RVSBP), RV weight (RVW) and lung injury/fibrotic scores were significantly increased in MCT group than sham-control (SC) that were reversed in MCT + PTU groups, whereas arterial oxygen saturation (%) and vasorelaxation/nitric oxide production of PA exhibited an opposite pattern of RVW among the groups (all p < 0.0001). The protein expressions of hypertrophic (ß-MHC)/pressure-overload (BNP)/oxidative-stress (NOX-1/NOX-2) biomarkers in RV and the protein expressions of intercellular signalling (GATAs3/4/6, Jagged1/2, notch1/2) and endMT markers (Snail/Zeb1/N-cadherin/vimentin/fibronectin/TGF-ß/α-SMA/p-Smad2) in lung parenchyma displayed an identical pattern of RVW among the groups (all p < 0.0001). Jagged-Notch-GATAs signalling, endMT markers and RVSBP that were increased in PAH were suppressed by PTU., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Purpose: To determine the side-to-side difference in intraindividual rotation alignment of patients with bilateral varus-type knee osteoarthritis (OA) and compare it with control subjects., Methods: This retrospective study enrolled 60 patients with bilateral varus-type knee OA and 50 control subjects. All cases underwent bilateral lower limb CT angiography. Bilateral femoral and tibial rotation alignment were measured, and the overall lower limb rotation was calculated by two different methods. Method 1 was calculated by subtracting angle of the femoral torsion from the tibial torsion and method 2 was determined by relative rotation of the femoral neck angle to bimalleolar angle. The intraindividual variance and differences between the two groups were analyzed., Results: Both OA and control samples showed significant differences between right and left for all measurements. Femoral torsion for control group was 10.4 ± 5.5°, tibial torsion was -22.1 ± 6.1°, and overall leg rotation by method 1 was -15.6 ± 7.2° and method 2 was -11.7 ± 8.2°. Femoral torsion, tibial torsion, method 1, and method 2 in the patients with OA were 8.2 ± 6.3°, -18.6 ± 4.1°, -14.9 ± 7.9°, and -10.4 ± 7.6°, respectively. Patients with OA showed a more pronounced retroversion in the femur ( p  = 0.008) and more internal rotation in the tibia ( p  <   0.001). No statistical significance of both methods was found between the two groups. Patients with OA had a greater median side-to-side absolute difference in all measurements, though the differences of both two methods of overall lower limb rotation were not statistically significant., Conclusions: The discrepancy of side-to-side differences of bilateral lower limb rotation ought to be noticed with caution in diagnosing and treating rotational deformities of the lower limb, especially for patients with bilateral knee OA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zheng, Wang, Jin, Huang, Yan, Peng, Zhou, Guo and Pan.)

This study investigated whether melatonin (Mel) would promote cisplatin to suppress the proliferation and growth of bladder cancer (BC) cells by inhibiting cellular prion protein (PrP C )-mediated cell stress and cell proliferation signaling. An immunohistochemical staining of tissue arrays from BC patients demonstrated that the PrP C expression was significantly upregulated from stage I to III BC ( p < 0.0001). The BC cellline of T24 was categorized into G1 (T24), G2 (T24 + Mel/100 μM), G3 (T24+cisplatin/6 μM), G4 (PrP C overexpression in T24 (i.e., PrP C-OE -T24)), G5 (PrP C-OE -T24+Mel), and G6 (PrP C-OE -T24+cisplatin). When compared with a human uroepithelial cell line (SV-HUC-1), the cellular viability/wound healing ability/migration rate were significantly increased in T24 cells (G1) and further significantly increased in PrP C-OE -T24 cells (G4); and they were suppressed in Mel (G2/G5) or cisplatin (G3/G6) treatment (all p < 0.0001). Additionally, the protein expressions of cell proliferation (PI3K/p-Akt/p-m-TOR/MMP-9/PrP C ), cell cycle/mitochondrial functional integrity (cyclin-D1/clyclin-E1/ckd2/ckd4/mitochondrial-cytochrome-C/PINK1), and cell stress (RAS/c-RAF/p-MEK1/2, p-ERK1/2) markers showed a similar pattern of cell viability among the groups (all p < 0.001). After the BC cell line of UMUC3 was implanted into nude mouse backs, by day 28 mthe BC weight/volume and the cellular levels of PrP C /MMP-2/MMP-9 were significantly, gradually reduced from groups one to four (all p < 0.0001). The protein expressions of cell proliferation (PI3K/p-Akt/p-m-TOR/MMP-9/PrP C ), cell cycle/mitophagy (cyclin-D1/clyclin-E1/ckd2/ckd4/PINK1), and cell stress (RAS/c-RAF/p-MEK1,2/p-ERK1,2) signaling were significantly, progressively reduced from groups one to four, whereas the protein expressions of apoptotic (Mit-Bax/cleaved-caspase-3/cleaved-PARP) and oxidative stress/mitochondrial damaged (NOX-1/NOX-2/cytosolic-cytochrome-C/p-DRP1) markers expressed an opposite pattern of cell proliferation signaling among the groups (all p < 0.0001). Mel-cisplatin suppressed BC cell growth/proliferation via inhibiting the PrP C in upregulating the cell proliferation/cell stress/cell cycle signaling.

Background: Cyclosporin A is a calcineurin inhibitor which has a narrow therapeutic window and high interindividual variability. Various population pharmacokinetic models have been reported; however, professional software and technical personnel were needed and the variables of the models were limited. Therefore, the aim of this study was to establish a model based on machine learning to predict CsA trough concentrations in Chinese allo-HSCT patients., Methods: A total of 7874 cases of CsA therapeutic drug monitoring data from 2069 allo-HSCT patients were retrospectively included. Sequential forward selection was used to select variable subsets, and eight different algorithms were applied to establish the prediction model., Results: XGBoost exhibited the highest prediction ability. Except for the variables that were identified by previous studies, some rarely reported variables were found, such as norethindrone, WBC, PAB, and hCRP. The prediction accuracy within ±30% of the actual trough concentration was above 0.80, and the predictive ability of the models was demonstrated to be effective in external validation., Conclusion: In this study, models based on machine learning technology were established to predict CsA levels 3-4 days in advance during the early inpatient phase after HSCT. A new perspective for CsA clinical application is provided.

Background: We tested the hypothesis that overexpression of cellular-prion-protein in adipose-derived mesenchymal stem cells (PrPC OE -ADMSCs) effectively protected the kidney against ischemia-reperfusion (IR) injury in rat., Methods: Part I of cell culture was categorized into A1(ADMSCs)/A2(ADMSCs+p-Cresol)/A3(PrPC OE in ADMSCs)/A4 (PrPC OE in ADMSCs+p-Cresol). Part II of cell culture was divided into B1(ADMSCs)/B2[ADMSCs+lipopolysaccharide (LPS)]/B3(PrPC OE in ADMSCs)/B4(PrPC OE in ADMSCs+LPS). Sprague-Dawley (SD) rats (n = 50) were equally categorized into groups 1 (sham-operated-control)/2 (IR)/3 (IR+ADMSCs/6.0 × 10 5 equally divided into bilateral-renal arteries and 6.0 × 10 5 intravenous administration by 1 h after IR)/4 [IR+PrPC OE -ADMSCs (identical dosage administered as group 3)]/5 [IR+silencing PRNP -ADMSCs (identical dosage administered as group 3)], and kidneys were harvested post-day 3 IR injury., Results: Part I results demonstrated that the cell viability at 24/48/72 h, BrdU uptake/number of mitDNA/APT concentration/mitochondrial-cytochrome-C+ cells and the protein expressions of ki67/PrPC at 72 h-cell culturing were significantly higher in PrPC OE -ADMSCs than in ADMSCs (all P < 0.001). The protein expressions of oxidative-stress (NOX-1/NOX2/NOX4/oxidized protein)/mitochondrial-damaged (p22-phox/cytosolic-cytochrome-C)/inflammatory (p-NF-κB/IL-1ß/TNF-α/IL-6)/apoptotic (cleaved caspase-3/cleaved-PARP) biomarkers were lowest in A1/A3 and significantly higher in A2 than in A4 (all P < 0.001). Part II result showed that the protein expressions of inflammatory (p-NF-κB/IL-1ß/TNF-α/IL-6)/apoptotic (cleaved caspase-3/cleaved-PARP) biomarkers exhibited an identical pattern of part I among the groups (all P < 0.001). The protein expressions of inflammatory (p-NF-κB/IL-1ß/TNF-α/MMP-9)/oxidative-stress (NOX-1/NOX-2/oxidized-protein)/mitochondrial-damaged (cytosolic-cytochrome-C/p22-phox)/apoptotic (cleaved caspase-3/cleaved-PARP/mitochondrial-Bx)/autophagic (beclin-1/ratio of LC3B-II/LC3B-I)/fibrotic (Smad3/TGF-ß) biomarkers and kidney-injury-score/creatinine level were lowest in group 1, highest in group 2, significantly higher in group 5 than in groups 3/4 (all P < 0.0001)., Conclusion: PrPC OE in ADMSCs rejuvenated these cells and played a cardinal role on protecting the kidney against IR injury., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

One-class classification aims to learn one-class models from only in-class training samples. Because of lacking out-of-class samples during training, most conventional deep learning based methods suffer from the feature collapse problem. In contrast, contrastive learning based methods can learn features from only in-class samples but are hard to be end-to-end trained with one-class models. To address the aforementioned problems, we propose alternating direction method of multipliers based sparse representation network (ADMM-SRNet). ADMM-SRNet contains the heterogeneous contrastive feature (HCF) network and the sparse dictionary (SD) network. The HCF network learns in-class heterogeneous contrastive features by using contrastive learning with heterogeneous augmentations. Then, the SD network models the distributions of the in-class training samples by using dictionaries computed based on ADMM. By coupling the HCF network, SD network and the proposed loss functions, our method can effectively learn discriminative features and one-class models of the in-class training samples in an end-to-end trainable manner. Experimental results show that the proposed method outperforms state-of-the-art methods on CIFAR-10, CIFAR-100 and ImageNet-30 datasets under one-class classification settings. Code is available at https://github.com/nchucvml/ADMM-SRNet.

The rampant of COVID-19 infodemic has almost been simultaneous with the outbreak of the pandemic. Many concerted efforts are made to mitigate its negative effect to information credibility and data legitimacy. Existing work mainly focuses on fact-checking algorithms or multi-class labeling models that are less aware of the intrinsic characteristics of the language. Nor is it discussed how such representations can account for the common psycho-socio-behavior of the information consumers. This work takes a data-driven analytical approach to (1) describe the prominent lexical and grammatical features of COVID-19 misinformation; (2) interpret the underlying (psycho-)linguistic triggers in terms of sentiment, power and activity based on the affective control theory; (3) study the feature indexing for anti-infodemic modeling. The results show distinct language generalization patterns of misinformation of favoring evaluative terms and multimedia devices in delivering a negative sentiment. Such appeals are effective to arouse people's sympathy toward the vulnerable community and foment their spreading behavior., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022.)

This study tested whether human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) treatment effectively protected the rat lung against acute respiratory distress syndrome (ARDS) injury, and benefits of early and dose-dependent treatment. Rat pulmonary epithelial cell line L2 (PECL2) were categorized into G1 (PECL2), G2 (PECL2 + healthy rat lung-derived extraction/50 mg/ml co-cultured for 24 h), G3 (PECL2 + ARDS rat lung-derived extraction/50 mg/ml co-cultured for 24 h), and G4 (condition as G3 + HUCDMSCs/1 × 10 5 /co-cultured for 24 h). The result showed that the protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IkB/NF-κB/IL-1β/TNF-α), oxidative-stress/mitochondrial-damaged (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/JNKs/JUN/cytosolic-cytochrome-C/cyclophilin-D/DRP1), and cell-apoptotic/fibrotic (cleaved-caspase 3/cleaved-PARP/TGF-β/p-Smad3) biomarkers were significantly increased in G3 than in G1/G2 and were significantly reversed in G4 (all P < 0.001), but they were similar between G1/G2. Adult male rats ( n = 42) were equally categorized into group 1 (normal control), group 2 (ARDS only), group 3 [ARDS + HUCDMSCs/1.2 × 10 6 cells intravenous administration at 3 h after 48 h ARDS induction (i.e., early treatment)], group 4 [ARDS + HUCDMSCs/1.2 × 10 6 cells intravenous administration at 24 h after 48 h ARDS induction (late treatment)], and group 5 [ARDS + HUCDMSCs/1.2 × 10 6 cells intravenous administration at 3 h/24 h after-48 h ARDS induction (dose-dependent treatment)]. By day 5 after ARDS induction, the SaO 2 %/immune regulatory T cells were highest in group 1, lowest in group 2, significantly lower in group 4 than in groups 3/5, and significantly lower in group 3 than in group 5, whereas the circulatory/bronchioalveolar lavage fluid inflammatory cells (CD11b-c+/LyG6+/MPO+)/circulatory immune cells (CD3-C4+/CD3-CD8+)/lung-leakage-albumin level/lung injury score/lung protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IκB-β/p-NF-κB/IL-1β/TNF-α)/fibrotic (p-SMad3/TGF-β), apoptosis (mitochondrial-Bax/cleaved-caspase-3)/oxidative-cell-stress (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/p-JNKs/p-cJUN)/mitochondrial damaged (cyclophilin-D/DRP1/cytosolic-cytochrome-C) biomarkers displayed an opposite pattern of SaO 2 % among the groups (all P < 0.0001). Early administration was superior to and two-dose counterpart was even more superior to late HUCDMSCs treatment for protecting the lung against ARDS injury.

Video summarization aims to generate a compact summary of the original video for efficient video browsing. To provide video summaries which are consistent with the human perception and contain important content, supervised learning-based video summarization methods are proposed. These methods aim to learn important content based on continuous frame information of human-created summaries. However, simultaneously considering both of inter-frame correlations among non-adjacent frames and intra-frame attention which attracts the humans for frame importance representations are rarely discussed in recent methods. To address these issues, we propose a novel transformer-based method named spatiotemporal vision transformer (STVT) for video summarization. The STVT is composed of three dominant components including the embedded sequence module, temporal inter-frame attention (TIA) encoder, and spatial intra-frame attention (SIA) encoder. The embedded sequence module generates the embedded sequence by fusing the frame embedding, index embedding and segment class embedding to represent the frames. The temporal inter-frame correlations among non-adjacent frames are learned by the TIA encoder with the multi-head self-attention scheme. Then, the spatial intra-frame attention of each frame is learned by the SIA encoder. Finally, a multi-frame loss is computed to drive the learning of the network in an end-to-end trainable manner. By simultaneously using both inter-frame and intra-frame information, our method outperforms state-of-the-art methods in both of the SumMe and TVSum datasets. The source code of the spatiotemporal vision transformer will be available at https://github.com/nchucvml/STVT.

The Coronavirus Disease 2019 (COVID-19) pandemic has shifted the focus of research worldwide, and more than 10 000 new articles per month have concentrated on COVID-19-related topics. Considering this rapidly growing literature, the efficient and precise extraction of the main topics of COVID-19-relevant articles is of great importance. The manual curation of this information for biomedical literature is labor-intensive and time-consuming, and as such the procedure is insufficient and difficult to maintain. In response to these complications, the BioCreative VII community has proposed a challenging task, LitCovid Track, calling for a global effort to automatically extract semantic topics for COVID-19 literature. This article describes our work on the BioCreative VII LitCovid Track. We proposed the LitCovid Ensemble Learning (LCEL) method for the tasks and integrated multiple biomedical pretrained models to address the COVID-19 multi-label classification problem. Specifically, seven different transformer-based pretrained models were ensembled for the initialization and fine-tuning processes independently. To enhance the representation abilities of the deep neural models, diverse additional biomedical knowledge was utilized to facilitate the fruitfulness of the semantic expressions. Simple yet effective data augmentation was also leveraged to address the learning deficiency during the training phase. In addition, given the imbalanced label distribution of the challenging task, a novel asymmetric loss function was applied to the LCEL model, which explicitly adjusted the negative-positive importance by assigning different exponential decay factors and helped the model focus on the positive samples. After the training phase, an ensemble bagging strategy was adopted to merge the outputs from each model for final predictions. The experimental results show the effectiveness of our proposed approach, as LCEL obtains the state-of-the-art performance on the LitCovid dataset. Database URL: https://github.com/JHnlp/LCEL., (© The Author(s) 2022. Published by Oxford University Press.)

Asthma is one of the common chronic respiratory diseases, and its incidence has been increasing worldwide in recent years. In the context of climate change, the frequency and intensity of extreme weather events are increasing. A large body of evidence suggests that exposure to extreme temperatures can increase the risk of asthma attacks, but the underlying mechanisms that trigger asthma attacks are still unclear. This study aims to systematically review the research progress on the association between extreme temperature and asthma attacks, and to elucidate the synergistic effects of extreme temperatures, indoor/outdoor environments, and individual vulnerabilities on asthma attacks. Additionally, this review discusses the potential mechanisms of asthma attacks triggered by extreme temperature, and highlights the important role of immune regulation and neuroregulation in the inflammatory response of asthma induced by extreme temperature. Moreover, we propose a potential mechanism framework to explain the disease pathogenesis of asthma which is induced by the interactions between extreme temperature and environmental factors, in order to provide a scientific basis for addressing the adverse impacts of extreme weather events and climate change.

This study optimized the field plate (FP) design (i.e., the number and positions of FP layers) of p-GaN power high-electron-mobility transistors (HEMTs) on the basic of simulations conducted using the technology computer-aided design software of Silvaco. Devices with zero, two, and three FP layers were designed. The FP layers of the HEMTs dispersed the electric field between the gate and drain regions. The device with two FP layers exhibited a high off-state breakdown voltage of 1549 V because of the long distance between its first FP layer and the channel. The devices were subjected to high-temperature reverse bias and high-temperature gate bias measurements to examine their characteristics, which satisfied the reliability specifications of JEDEC.

Background: This study tested the hypothesis that overexpression of cellular prion protein in endothelial progenitor cells (PrPc OE -EPCs), defined as "rejuvenated EPCs," was superior to EPCs for salvaging the critical limb ischemia (CLI) induced after 28-day chronic kidney disease (CKD) induction in rat., Methods and Results: Cell viability and flow cytometric analyses of early/late apoptosis/total-intracellular ROS/cell cycle (sub-G1, G2/M phase) were significantly higher in EPCs + H 2 O 2 than in EPCs that were significantly reversed in PrPc OE -EPCs + H 2 O 2 (all p < 0.001). The protein expressions of inflammation (IL-1ß/IL-6/MMP-9/p-NF-κB) were significantly increased in EPC + TNF-α than in EPCs that were significantly reversed in PrPc OE -EPCs + TNF-α (all p < 0.001). Adult-male SD rats (n = 8/each group) were categorized into group 1 (sham-operated control), group 2 (CKD + CLI), group 3 [CKD + CLI + EPCs by intravenous (0.6 × 10 5 )/intra-muscular (0.6 × 10 5 ) injections at 3 h after CLI induction], group 4 (CKD + CLI + PrPc OE -EPCs/dose-administration as group 3) and group 5 (CKD + CLI + siPrnp-EPCs/dose-administration as group 3). By day 14 after CLI induction, the ratio of ischemia to normal blood flow (INBF) in CLI area was highest in group 1/lowest in group 2/significantly higher in group 4 than in groups 3/5 and significantly higher in group 3 than in group 5 (all p < 0.0001). Histopathology demonstrated that the angiogenesis (number of small vessels/CD31 + cells) exhibited a similar trend, whereas the fibrosis/kidney injury score exhibited an opposite pattern of INBF among the groups (all p < 0.0001). The protein expressions of angiogenesis (SDF-1α/VEGF/CXCR4)/cell-stress signaling (p-PI3K/p-Akt/p-m-TOR) were significantly and progressively increased from groups 1-4 that were reversed in group 5 (all p < 0.0001). The protein expressions of fibrotic (p-Smad3/TGF-ß)/oxidative-stress (NOX-1/NOX-2/oxidized-protein)/apoptotic (mitochondrial-Bax/cleaved caspase3/cleaved PARP)/mitochondrial-damaged (cytosolic-cytochrome-C) biomarkers displayed an opposite pattern of INBF among the groups (all p < 0.0001)., Conclusion: PrPc OE -EPCs were superior to EPCs only therapy for salvaging the CLI., (© 2022. The Author(s).)

Introduction: The introduction of antiviral therapy in chronic hepatitis B (CHB) infection depends on precise evaluation of hepatic lesions. Total serum bile acids (TSBAs) are highly sensitive in monitoring liver dysfunction. We evaluated the predictive role of TSBAs for hepatic lesions in CHB patients with borderline alanine aminotransferase (ALT) and high level of hepatitis B virus (HBV) DNA copies., Methodology: 328 CHB patients were enrolled, 241 were hepatitis B e antigen (HBeAg)-positive and 87 were HBeAg-negative. Patients were further divided into two entities according to inflammation/fibrosis evaluated by liver biopsy, low-grade (inflammation grade < 2 and fibrosis stage < 2) and high-grade (inflammation grade ≥ 2 or/and fibrosis stage ≥ 2) cohorts. TSBAs were compared with noninvasive tools including aspartate aminnotransferase (AST)-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) and red cell distribution width (RDW)-to-platelet ratio (RPR) to predict high-grade hepatic lesions in CHB subgroups., Results: TSBAs, APRI, FIB-4 and RPR were statistically different between low- and high-grade patients in HBeAg-positive cohort. Only TSBAs showed significant difference between low and high grade in HBeAg-negative patients. Similarly, APRI, FIB-4 and RPR were correlated with different division of inflammation/fibrosis only in HBeAg-positive while TSBAs were correlated with inflammation/fibrosis levels in both HBeAg-positive and HBeAg-negative groups. Of the four indicators, the receiver operating characteristic (ROC) curve analysis showed that TSBAs have the maximum AUC (area under the curve) in HBeAg-negative group but the minimum in HBeAg-positive cohort., Conclusions: TSBAs can be used for predicting antiviral therapy in CHB patients with HBeAg-negative, borderline ALT and high HBV DNA., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Ran Xie, Jiao Li, Hao Zhang, Ling-mei Wang, Cheng-rong Huang, Li-wen Chen.)

Purpose: Venetoclax (VEN), an anti-tumor drug that is a substrate of cytochrome P450 3A enzyme (CYP3A4), is used to treat leukemia. Voriconazole (VCZ) is an antifungal medication that inhibits CYP3A4. The goal of this study is to predict the effect of VCZ on VEN exposure., Method: Two physiological based pharmacokinetics (PBPK) models were developed for VCZ and VEN using the bottom-up and top-down method. VCZ model was also developed to describe the effect of CYP2C19 polymorphism on its pharmacokinetics (PK). The reversible inhibition constant (K i ) of VCZ for CYP3A4 was calibrated using drug-drug interaction (DDI) data of midazolam and VCZ. The clinical verified VCZ and VEN model were used to predict the DDI of VCZ and VEN at clinical dosing scenario., Result: VCZ model predicted VCZ exposure in the subjects of different CYP2C19 genotype and DDI related fold changes of sensitive CYP3A substrate with acceptable prediction error. VEN model can capture PK of VEN with acceptable prediction error. The DDI PBPK model predicted that VCZ increased the exposure of VEN by 4.5-9.6 fold. The increase in VEN exposure by VCZ was influenced by subject's CYP2C19 genotype. According to the therapeutic window, VEN dose should be reduced to 100 mg when co-administered with VCZ., Conclusion: The PBPK model developed here could support individual dose adjustment of VEN and DDI risk assessment. Predictions using the robust PBPK model confirmed that the 100 mg dose adjustment is still applicable in the presence of VCZ with high inter-individual viability., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms., Methods and Results: MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and CD127+ cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation., Conclusion: IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: The COVID-19 pandemic has increasingly accelerated the publication pace of scientific literature. How to efficiently curate and index this large amount of biomedical literature under the current crisis is of great importance. Previous literature indexing is mainly performed by human experts using Medical Subject Headings (MeSH), which is labor-intensive and time-consuming. Therefore, to alleviate the expensive time consumption and monetary cost, there is an urgent need for automatic semantic indexing technologies for the emerging COVID-19 domain., Results: In this research, to investigate the semantic indexing problem for COVID-19, we first construct the new COVID-19 Semantic Indexing dataset, which consists of more than 80 thousand biomedical articles. We then propose a novel semantic indexing framework based on the multi-probe attention neural network (MPANN) to address the COVID-19 semantic indexing problem. Specifically, we employ a k-nearest neighbour based MeSH masking approach to generate candidate topic terms for each input article. We encode and feed the selected candidate terms as well as other contextual information as probes into the downstream attention-based neural network. Each semantic probe carries specific aspects of biomedical knowledge and provides informatively discriminative features for the input article. After extracting the semantic features at both term-level and document-level through the attention-based neural network, MPANN adopts a linear multi-view classifier to conduct the final topic prediction for COVID-19 semantic indexing., Conclusion: The experimental results suggest that MPANN promises to represent the semantic features of biomedical texts and is effective in predicting semantic topics for COVID-19 related biomedical articles., (© 2022. The Author(s).)

A p-GaN HEMT with an AlGaN cap layer was grown on a low resistance SiC substrate. The AlGaN cap layer had a wide band gap which can effectively suppress hole injection and improve gate reliability. In addition, we selected a 0° angle and low resistance SiC substrate which not only substantially reduced the number of lattice dislocation defects caused by the heterogeneous junction but also greatly reduced the overall cost. The device exhibited a favorable gate voltage swing of 18.5 V (@I GS = 1 mA/mm) and an off-state breakdown voltage of 763 V. The device dynamic characteristics and hole injection behavior were analyzed using a pulse measurement system, and Ron was found to increase and V TH to shift under the gate lag effect.

In this study, we investigated enhance mode (E-mode) p-GaN/AlGaN/GaN high-electron-mobility transistors (HEMTs) with an Al 0.5 GaN etch-stop layer. Compared with an AlN etch-stop layer, the Al 0.5 GaN etch-stop layer not only reduced lattice defects but engendered improved DC performance in the device; this can be attributed to the lattice match between the layer and substrate. The results revealed that the Al 0.5 GaN etch-stop layer could reduce dislocation by 37.5% and improve device characteristics. Compared with the device with the AlN etch-stop layer, the p-GaN HEMT with the Al 0.5 GaN etch-stop layer achieved a higher drain current on/off ratio (2.47 × 10 7 ), a lower gate leakage current (1.55 × 10 -5 A/mm), and a lower on-state resistance (21.65 Ω·mm); moreover, its dynamic R ON value was reduced to 1.69 (from 2.26).

In this study, the effects of process parameters (feed rate, spindle speed, and ultrasonic power level) on the cutting force and delamination in the ultrasonic vibration-assisted drilling of carbon fiber-reinforced plastics (CFRPs) have been investigated. A series of drilling tests under various conditions defined by the design of experiment technique were conducted. The evolution of the cutting force during drilling cycles was measured and analyzed. Experimental analysis results based on the Taguchi method and analysis of variance show that the spindle speed is an influential factor affecting the cutting force with a contribution of 75.36%, and the feed rate significantly affects the delamination damage with a contribution of 46.57%. In addition, the cutting force was found to increase with drilling cycles at different rates, which depends on the process parameters used in drilling. The evolution behavior of cutting force was well fitted based on the process parameters by proposed regression models. Experimental validation indicates that the predicted forces show reasonable agreement with measured values under different conditions and reveal good prediction performances, with a root mean square error of 5.6 and a mean absolute percentage error of 5.8%. In drilling tests with variable cutting conditions, the evolution of the cutting forces predicted based on the selected parameters was successfully verified when compared with the measured results, with RMSE and MAPE values of 7.55 and 5.61%, respectively. As a conclusion, this predictive model provides an effective basis for selecting appropriate drilling parameters to suppress the cutting force on CFRP composites.