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Previous studies have found that once seedlings break the soil, light can induce the degradation of the key ethylene signaling element ethylene insensitive 3 (EIN3), so as to indirectly inhibit the synthesis of ethylene. Ethylene is the most important hormone in phosphorus absorption by plants, which induces the expression of acid phosphatase (APase) and phosphorus starvation response genes. Therefore, it might be speculated that changes in light intensity could regulate phosphorus absorption to some degree. However, there are few reports on the mechanism by which light intensity regulates phosphorus metabolism. In this study, the effects of different light intensities on phosphorus assimilation and metabolism in plants were studied. The results showed that relatively low light intensity could promote the secretion of APase, so as to increase the concentration of plant total phosphorus and cellular Pi. However, the low light intensity may also inhibit plant growth. Among the three species, oilseed rape was the most sensitive to the low light intensity. The steady-state level of the EIN3 protein decreased significantly under a relatively high light intensity; while the ethylene level also decreased under the high light intensity. Therefore, appropriate reductions in light intensity may simultaneously promote phosphorus assimilation and maintain plant growth.

Electrocatalytic oxygen evolution reaction (OER) is not only a half-reaction of water-splitting to produce hydrogen, but also an important half-reaction of electrocatalytic carbon dioxide reduction, nitrogen reduction, nitrate reduction, organic small molecule reduction, and metal-air batteries. The OER process is driven by a four-electron mechanism. Due to the slow and complex kinetics of the electrocatalytic OER and its strong oxidation characteristics, studying the oxidative reconstruction rules and catalytic mechanisms of electrode materials in the OER process is of great significance to improve the efficiency of the OER. As a kind of metal-free electrode materials, carbon materials are widely used in electrocatalysis, which has become a potential electrocatalyst for OER due to their low price, abundant reserves, and high activity stability. At present, oxygen-containing functional groups on the surface of carbon materials have been proven to be active sites for OER. However, the deactivation mechanism of carbon materials at higher oxidation potentials during the OER process remains unclear due to a lack of understanding of the active site evolution mechanism. Correctly identifying the active sites of carbon materials under oxygen evolution conditions has become a research hotspot in the field. However, ex-situ characterization techniques such as X-ray diffraction (XRD) and scanning electron microscopy (SEM) are difficult to reflect the catalytic behavior of carbon materials under working conditions. In this study, differential electrochemical mass spectrometry (DEMS) was used to monitor the structural changes of carbon material during the OER process with graphite as the model material. The effects of applied voltage and pH value of electrolyte on graphite oxidation were investigated respectively. By changing the applied potential and the pH value of the electrolyte, we found that graphite firstly oxidizes itself to form oxygen-containing functional groups under acidic (pH 0), neutral (pH 7), and alkaline (pH 14) conditions. As the potential increases, the graphite begins to produce CO2 and CO at 1.6 V vs. RHE over the full pH value range, and the content of CO2 gradually augments as the potential increases. The generation potential of O2 is higher than that of CO2 under acidic condition, and the opposite is true under alkaline condition. Therefore, graphite can be used as an OER catalyst under alkaline condition in a certain potential range. This work not only reveals the structural transformation rules and corresponding evolution products of carbon materials in the full pH value range under electrochemical oxidation conditions, but also proposes a feasible potential operating range when carbon materials are used as OER catalysts.

The coexistence of anxiety or depression with coronary heart disease (CHD) is a significant clinical challenge in cardiovascular medicine. Recent studies have indicated that hypothalamic-pituitary-adrenal (HPA) axis activity could be a promising focus in understanding and addressing the development of treatments for comorbid CHD and anxiety or depression. The HPA axis helps to regulate the levels of inflammatory factors, thereby reducing oxidative stress damage, promoting platelet activation, and stabilizing gut microbiota, which enhance the survival and regeneration of neurons, endothelial cells, and other cell types, leading to neuroprotective and cardioprotective benefits. This review addresses the relevance of the HPA axis to the cardiovascular and nervous systems, as well as the latest research advancements regarding its mechanisms of action. The discussion includes a detailed function of the HPA axis in regulating the processes mentioned. Above all, it summarizes the therapeutic potential of HPA axis function as a biomarker for coronary atherosclerotic heart disease combined with anxiety or depression.

Xinyu mandarin is popular for its good flavor, but its flavor deteriorates during postharvest storage. To better understand the underlying basis of this change, the dynamics of the sensory profiles were investigated throughout fruit ripening and storage. Sweetness and sourness, determined especially by sucrose and citric acid content, were identified as the key sensory factors in flavor establishment during ripening, but not in flavor deterioration during storage. Postharvest flavor deterioration is mainly attributed to the reduction of retronasal aroma and the development of off-flavor. Furthermore, sugars, acids and volatile compounds were analyzed. Among the 101 detected volatile compounds, 10 changed significantly during the ripening process. The concentrations of 15 volatile components decreased during late postharvest storage, among which α-pinene and d-limonene were likely to play key roles in the reduction of aroma. Three volatile compounds were found to increase during storage, associated with off-flavor development.

We report a step-economic strategy for the direct synthesis of novel polycyclic N-heterocycle-fused naphthoquinones by merging intramolecular oxidative coupling and cascade [4 + 2] cycloaddition. In the protocol, mechanistic investigations suggest that the cascade reaction involves the intermediate spiro polycyclic N-heterocycles and [4 + 2] cycloaddition processes. This protocol is featured with moderate to excellent yields, wide substrate scope, and divergent structures of products. In addition, the photophysical properties of the synthesized products were evaluated. These products exhibit interesting fluorescence properties, and surprisingly, the compounds have the ability to selectively recognize trifluoroacetic acid.

Background: Weaning patients from mechanical ventilation is a critical clinical challenge post cardiac surgery. The effective liberation of patients from the ventilator significantly improves their recovery and survival rates. This study aimed to develop and validate a clinical prediction model to evaluate the likelihood of successful extubation in post-cardiac surgery patients. Method: A predictive nomogram was constructed for extubation success in individual patients, and receiver operating characteristic (ROC) and calibration curves were generated to assess its predictive capability. The superior performance of the model was confirmed using Delong's test in the ROC analysis. A decision curve analysis (DCA) was conducted to evaluate the clinical utility of the nomogram. Results: Among 270 adults included in our study, 107 (28.84%) experienced delayed extubation. A predictive nomogram system was derived based on five identified risk factors, including the proportion of male patients, EuroSCORE II, operation time, pump time, bleeding during operation, and brain natriuretic peptide (BNP) level. Based on the predictive system, five independent predictors were used to construct a full nomogram. The area under the curve values of the nomogram were 0.880 and 0.753 for the training and validation cohorts, respectively. The DCA and clinical impact curves showed good clinical utility of this model. Conclusion: Delayed extubation and weaning failure, common and potentially hazardous complications following cardiac surgery, vary in timing based on factors such as sex, EuroSCORE II, pump duration, bleeding, and postoperative BNP reduction. The nomogram developed and validated in this study can accurately predict when extubation should occur in these patients. This tool is vital for assessing risks on an individual basis and making well-informed clinical decisions.

Background: Sepsis is a life-threatening condition characterized by an aberrant host response to infection, resulting in multi-organ dysfunction. The application of currently available prognostic indicators for sepsis in primary hospitals is challenging. In this retrospective study, we established a novel index, the neutrophil-to-lymphocyte-to-monocyte ratio (NLMR), based on routine blood examination upon admission, and assessed its prognostic value for early mortality risk in adult patients with septic shock. Methods: This study included clinical data from adult patients with septic shock who were admitted to the hospital between January 1, 2018, and December 31, 2022. Training and validation sets were constructed, and patients were categorized into “survival” and “death” groups based on their survival status within the 28-day hospitalization period. Baseline data, including demographic characteristics and comorbidities, and laboratory results, such as complete blood count parameters, were collected for analysis. The Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were documented.The NLMR was determined through the utilization of multivariate binary logistic regression analysis, leading to the development of a risk model aimed at predicting early mortality in adult patients suffering from septic shock. Results: Overall, 112 adult patients with septic shock were enrolled in this study, with 84 and 28 patients in the training and validation sets, respectively. Multivariate binary logistic analysis revealed that the neutrophil, lymphocyte, and monocyte counts independently contributed to the mortality risk (odds ratios = 1.22, 0.08, and 0.16, respectively). The NLMR demonstrated an area under the receiver operating characteristic curve (ROC-AUC) of 0.83 for internal validation in the training set and 0.97 for external validation in the validation set. Both overall model quality values were significantly high at 0.74 and 0.91, respectively (P

Objective To derive the paternity index （PI） calculation formula of the alleged father （AF） when the AF is a relative （parent/child， siblings， grandparent/grandchild， uncle/nephew， first cousins） of the child’s biological mother. Methods For the case when the AF is related to the child’s biological mother， the existence of the relationship in the numerator and denominator hypothesis of PI was considered. The genotype frequency of the AF was calculated by using the frequency formula in which the mother’s genotype was considered， while the random male in the denominator was substituted as another relative of the mother’s same rank. The PI calculation formula was derived to eliminate the effect of the relationship between AF and the child’s biological mother. Results When the AF and the biological mother have first， second and tertiary kinship， a more conservative PI was obtained from the PI calculation formula derived in this study compared with the PI calculation method which did not consider kinship. Conclusion The calculation method provided in this study can eliminate the effect of the relation of the AF and mother on the PI in incest cases， to obtain more accurate and conservative identification conclusions.

Background and Objectives: Prolactinomas are the most common pituitary adenomas, comprising 30–50% of such tumors. These adenomas cause hyperprolactinemia, leading to decreased fertility, reduced energy and libido, and galactorrhea. Diagnosing and treating prolactinomas in adolescents present unique challenges, as symptoms may be confused with age-related developmental variations. This case report explores the outcomes of early surgical intervention in an adolescent with a prolactinoma. Materials and Methods: A 14-year-old female presented delayed menarche and absent pubertal development. Initial evaluation revealed hyperprolactinemia (228.37 ng/mL) with normal estradiol levels. Initial management through observation was adopted, but persistent amenorrhea and severe headaches prompted further investigation. Magnetic resonance imaging revealed a cystic pituitary mass with apoplexy. Due to concerns regarding delayed puberty and the need for rapid normalization of prolactin levels, the patient underwent transsphenoidal surgery. Results: After operation, prolactin levels normalized, menarche occurred within three months, and secondary sexual characteristics developed within eight months. Pathology confirmed a pituitary adenoma with a high Ki-67 index (15%). Conclusions: Early surgical intervention for prolactinomas in adolescents can achieve successful biochemical remission and resolution of endocrine symptoms. Adolescents, particularly those with a high Ki-67 index and potential resistance to dopamine agonists, may benefit from prompt surgical management, resulting in improved clinical outcomes and complete tumor resection.

Organoid is a new research tool that has gradually emerged in recent years. They promise to have a broad application prospect in the fields of disease development, drug screening, new drug development, per-sonalized medicine and other fields. Nowadays, the colorectal cancer organoid model has become relatively mature. This paper reviews the common models in colorectal cancer research and the construction and applica-tion of colorectal cancer organoids.

Abstract Background The eighth edition of the American Joint Committee on Cancer (AJCC) staging system for lung cancer adopts new criteria for tumor size, and for determining pTis, pT1a(mi), and pT1a. The latter is based on the size of stromal invasion. It is quite challenging for lung pathologists. Methods All patients who had undergone surgical resection for pulmonary adenocarcinoma (ADC) at Chung Shan Medical University Hospital between January 2014 and April 2018 were reviewed, and restaged according to the eighth AJCC staging system. The clinical characteristics and survival of patients with tumor stage 0 (pTis), I or II were analyzed. Results In total, 376 patients were analyzed. None of the pTis, pT1a(mi), or pT1a tumors recurred during the follow‐up period up to 5 years, but pT1b, pT1c, pT2a, and pT2b tumors all had a few tumor recurrences (p

Abstract Purpose Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a fast-growing incidence in recent decades. HOTAIR as a long non-coding RNA has been shown to be highly expressed in papillary thyroid cancer tissues with only a limited understanding of its functional roles and downstream regulatory mechanisms in papillary thyroid cancer cells. Methods We applied three thyroid cancer cell lines (MDA-T32, MDA-T41 and K1) to investigate the phenotypic influence after gain or loss of HOTAIR. The Cancer Genome Atlas (TCGA) database were utilised to select candidate genes possibly regulated by HOTAIR with validation in the cellular system and immunohistochemical (IHC) staining of PTC tissues. Results We observed HOTAIR was highly expressed in MDA-T32 cells but presents significantly decreased levels in MDA-T41 and K1 cells. HOTAIR knockdown in MDA-T32 cells significantly suppressed proliferation, colony formation, migration with cell cycle retardation at G1 phase. On the contrary, HOTAIR overexpression in MDA-T41 cells dramatically enhanced proliferation, colony formation, migration with cell cycle driven toward S and G2/M phases. Similar phenotypic effects were also observed as overexpressing HOTAIR in K1 cells. To explore novel HOTAIR downstream mechanisms, we analyzed TCGA transcriptome in PTC tissues and found DLX1 negatively correlated to HOTAIR, and its lower expression associated with reduced progression free survival. We further validated DLX1 gene was epigenetically suppressed by HOTAIR via performing chromatin immunoprecipitation. Moreover, IHC staining shows a significantly stepwise decrease of DLX1 protein from normal thyroid tissues to stage III PTC tissues. Conclusions Our study pointed out that HOTAIR is a key regulator of cellular malignancy and its epigenetic suppression on DLX1 serves as a novel biomarker to evaluate the PTC disease progression.

A novel coagulase-negative Staphylococcus strain (H164T) was isolated from soymilk in Taiwan. Comparative sequence analysis of the 16S rRNA gene revealed that the H164T strain is a member of the genus Staphylococcus. We used multilocus sequence analysis (MLSA) and phylogenomic analyses to demonstrate that the novel strain was closely related to Staphylococcus gallinarum, Staphylococcus nepalensis, Staphylococcus cohnii, and Staphylococcus urealyuticus. The average nucleotide identity and digital DNA-DNA hybridization values between H164T and its closest relatives were T strain could also be distinguished from its closest relatives by the fermentation of d-fructose, d-maltose, d-trehalose, and d-mannitol, as well as by the activities of α-glucosidase and alkaline phosphatase. The major cellular fatty acids were C15:0 iso and C15:0 anteiso, and the predominant menaquinones were MK-7 and MK-8, respectively. The major cellular fatty acids and predominant menaquinones were C15:0 iso and C15:0 anteiso and MK-7 and MK-8, respectively. In conclusion, this strain represents a novel species, named Staphylococcus hsinchuensis sp. nov., with the type strain H164T (=BCRC 81404T = NBRC 116174T).

Abstract Background Pharynx and larynx cancers (PLCs) are the top killer cancers in head and neck and significantly affect the quality of life of patients. A detailed study examining the disease burden and risk factors of PLCs is lacking. Methods Data on mortality and disability-adjusted life-years (DALYs) were extracted from the Global Burden of Disease Study 2019. The estimated annual percentage change (EAPC) of the age-standardized mortality rate was calculated using a generalized linear model with a Gaussian distribution. Mortality and DALYs were stratified according to the sociodemographic index (SDI), age, gender, and risk factors. The association between the SDI and mortality rate was measured using Spearman’s correlation. Results Between 1990 and 2019, the total number of deaths due to PLCs increased by 60.7% (95% confidence intervals: 39.32 to 66.8), from 192.38 thousand in 1990 to 309.16 thousand in 2019, and the total DALYs due to PLCs increased by 49.41% (95% confidence intervals: 30.15 to 53.27), from 5.91 million in 1990 to 8.83 million in 2019. The age-standardized mortality rate declined for larynx cancer (from 2.19 in 1990 to 1.49 in 2019) and nasopharynx cancer (1.26 to 0.86) but increased slightly for other pharynx cancer (1.25 to 1.37). The death number of PLCs was significantly higher in men aged 50 to 70 years, which accounts for 46.05% and 43.83% of the total deaths in 1990 and 2019, respectively. Low and low-middle countries had the greatest age-standardized mortality rate for larynx and other pharynx cancer, while low-middle and middle countries dominated for nasopharynx cancer. The leading risk factors for PLCs were smoking and alcohol use, which account for 37.92% and 58.84% in total DALYs rate of PLCs, and the influence of risk factors was significant in men. Conclusion The total number of deaths and DALYs due to PLCs increased from 1990 to 2019. Countries with relatively low SDI and middle-aged and older men had the greatest burden of PLCs. Building better health care systems in relatively low SDI countries and improving strategies of smoking and alcohol control should be a priority in health policy.

Information entropy can be used for investigating the critical fluctuation phenomenon by describing multiplicity fluctuations in heavy-ion collisions. In this study, a multiphase transport (AMPT) model in the default version (AMPT-DEF) and with the string melting (AMPT-SM) were used as event generators to simulate the Au+Au reaction at different incident energies. Owing to the influence of the distribution bin number in extracting its information entropy, two methods, i.e., data binning and weighting factors, were proposed to correct the information entropy analysis. The comparison between information entropy and kurtosis also reflects the necessity to correct the information entropy analysis. The corrected information entropy of net-proton multiplicity was analyzed in central Au+Au collisions at sNN= 4.7, 6.4, 7.7, 8.8, 11.5, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 140, 170, and 200 GeV with the impact parameter b=3 fm. The results indicated that the fluctuations of net-proton multiplicity were essentially identical at collision energies ranging from sNN= 4.7 GeV to sNN= 200 GeV in the same model. No critical fluctuation phenomenon was found in the central Au+Au collisions simulated using the AMPT models, similar to the case of the AMPT model, which does not have. Comparing the information entropy of AMPT-SM to AMPT-DEF, the effect of partonic phase leads to a bigger fluctuation, indicating that the corrected information entropy can be a useful probe to explore the phase transition. The mid-rapidity net-proton multiplicity information entropy was also calculated, and the results led to the same conclusion. The corrected information entropy may be useful for investigating critical fluctuations, which is important for exploring critical endpoint.

Objectives: This study aimed to provide detailed genetic characterization of Tn6636, a multidrug-resistant and composite mobile element, in clinical isolates of Staphylococcus aureus. Methods: A total of 112 ermB-positive methicillin-susceptible S. aureus (MSSA) and 224 ermB-positive methicillin-resistant S. aureus (MRSA) isolates collected from 2000 to 2015 were tested for the presence of Tn6636. Detection of the plasmids harboring Tn6636 was performed by S1 nuclease digestion pulsed-field gel electrophoresis (PFGE) analysis, conjugation test, and whole genome sequencing (WGS). Results: Prevalence of Tn6636 in MSSA is higher than that in MRSA. Ten MSSA isolates and 10 MRSA isolates carried Tn6636. The 10 MSSA isolates belonged to three sequence types (ST), including ST7 (n = 6), ST5 (n = 3), and ST59 (n = 1). The 10 MRSA isolates belonged to ST188 (n = 8) and ST965 (n = 2). Analysis of plasmid sequences revealed that Tn6636 was harbored by six different mosaic plasmids. In addition to resistance genes, some plasmids also harbored toxin genes. Conclusion: The presence of multi-resistant Tn6636 in plasmids of both MSSA and MRSA with various STs suggests its broad dissemination. Results indicate that Tn6636 has existed for at least 16 years in Taiwan. The mosaic plasmids harboring Tn6636 can be transferred by conjugation. Ongoing surveillance of Tn6636 is essential to avoid continued spreading of resistant plasmids.

Abstract Objectives We aimed to elucidate the moderating effect of volunteer participation on the association between insomnia and subjective well-being. Methods This was a community-based, cross-sectional study that targeted community-dwelling older adults aged ≥ 65 years in Yilan city, Taiwan. Whether individuals had volunteered in the past month was asked. Insomnia was measured using the Athens Insomnia Scale-5. Subjective well-being was evaluated using self-rated health, self-rated happiness, the physical component summary (PCS), and the mental component summary (MCS) of Short-form 12. Interaction terms between volunteer participation and insomnia were examined to test the moderating effect of volunteer participation on subjective well-being. Results In total, 3,875 participants were included in the study. After controlling for confounders, older adults with insomnia were more likely to have poor subjective well-being, except with respect to PCS. By contrast, volunteering was associated with a low risk of association between self-rated health and happiness. The interaction terms for volunteering with self-rated happiness (p = 0.03) and the MCS (p = 0.02) were significant. The association between insomnia and poor self-rated happiness among volunteers (odds ratio [OR] = 3.91, 95% confidence interval [CI] = 1.85–8.28) was significantly stronger than that in non-volunteers (OR = 1.48, 95% CI = 1.18–1.86). However, insomnia was linked with poor MCS in non-volunteers (OR = 1.53, 95% CI = 1.21–1.94), but not in volunteers (OR = 0.64, 95% CI = 0.27–1.50). Discussion Volunteer participation moderated the association between insomnia and subjective well-being; specifically, volunteering strengthened the association between insomnia and poor self-rated happiness but mitigated the relationship between insomnia and poor MCS.

ABSTRACT: Objectives: This study aimed to clarify the characteristics of Tn7-derivatives transposons in MDR Proteus mirabilis strains isolated from anal swabs of chicken and swine in China from 2015–2020. Methods: The Tn7 tnsA gene was screened in 207 P. mirabilis isolates by polymerase chain reaction (PCR). These strains were subjected to antimicrobial susceptibility testing. Illumina Hiseq (200 × coverage) was used for genome sequencing. Transposon maps were completed by PCR and Sanger sequencing and analysed by BLAST. Results: The Tn7 tnsA gene was detected in 21 strains by PCR. Eight novel Tn7-derivatives, named Tn6667, Tn6668, Tn6669, Tn6670, Tn7095, Tn7096, Tn7097 and Tn7098, were characterised. Three types of hybrid class 2/1 integrons were found at the right end of Tn7 derivatives. A novel Tn7-like transposon Tn6666 with an active integrase gene intI2, whose transposition module shows 93% nucleotide identity to the corresponding region of Tn7, was characterised in three strains. Tn6666 is also found next to Tn7097 or Tn7098 in the chromosomes of two clonally related P. mirabilis strains. The number of resistance genes carried by the novel transposons varied from 1 to 18. A novel variant of class A extended-spectrum beta-lactamase gene, blaPER-16, with eight base substitutions compared with blaPER-12, was harboured by Tn7098. Conclusion: Our study characterised diverse novel Tn7-derivatives and a new Tn7-like transposon in P. mirabilis. An active integrase gene intI2 might promote the diversification of Tn7-like transposons. More attention should be paid to the prevalence and evolution of Tn7-derivatives and Tn7-like transposons and antimicrobial resistance genes they carry.

IntroductionThe continued emergence and spread of multidrug-resistant (MDR) bacterial pathogens require a new strategy to improve the efficacy of existing antibiotics. Proline-rich antimicrobial peptides (PrAMPs) could also be used as antibacterial synergists due to their unique mechanism of action.MethodsUtilizing a series of experiments on membrane permeability, In vitro protein synthesis, In vitro transcription and mRNA translation, to further elucidate the synergistic mechanism of OM19r combined with gentamicin.ResultsA proline-rich antimicrobial peptide OM19r was identified in this study and its efficacy against Escherichia coli B2 (E. coli B2) was evaluated on multiple aspects. OM19r increased antibacterial activity of gentamicin against multidrug-resistance E. coli B2 by 64 folds, when used in combination with aminoglycoside antibiotics. Mechanistically, OM19r induced change of inner membrane permeability and inhibited translational elongation of protein synthesis by entering to E. coli B2 via intimal transporter SbmA. OM19r also facilitated the accumulation of intracellular reactive oxygen species (ROS). In animal models, OM19r significantly improved the efficacy of gentamicin against E. coli B2.DiscussionOur study reveals that OM19r combined with GEN had a strong synergistic inhibitory effect against multi-drug resistant E. coli B2. OM19r and GEN inhibited translation elongation and initiation, respectively, and ultimately affected the normal protein synthesis of bacteria. These findings provide a potential therapeutic option against multidrug-resistant E. coli.

ObjectiveTo evaluate the efficacy of acupuncture in treating Parkinson’s disease-related constipation (PDC).Materials and methodsThis was a randomized, controlled trial in which patients, outcome assessors, and statisticians were all blinded. Seventy-eight eligible patients were randomly assigned to either the manual acupuncture (MA) or sham acupuncture (SA) groups and received 12 sessions of treatment over a 4-week period. Following treatment, patients were monitored until the eighth week. The primary outcome was the change in weekly complete spontaneous bowel movements (CSBMs) from baseline after treatment and follow-up. The Constipation Symptom and Efficacy Assessment Scale (CSEAS), the Patient-Assessment of Constipation Quality of Life questionnaire (PAC-QOL), and the Unified Parkinson’s Disease Rating Scale (UPDRS) were used as secondary outcomes.ResultsIn the intention-to-treat analysis, 78 patients with PDC were included, with 71 completing the 4-week intervention and 4-week follow-up. When compared to the SA group, weekly CSBMs were significantly increased after treatment with the MA group (P < 0.001). Weekly CSBMs in the MA group were 3.36 [standard deviation (SD) 1.44] at baseline and increased to 4.62 (SD, 1.84) after treatment (week 4). The SA group’s weekly CSBMs were 3.10 (SD, 1.45) at baseline and 3.03 (SD, 1.25) after treatment, with no significant change from baseline. The effect on weekly CSBMs improvement in the MA group lasted through the follow-up period (P < 0.001).ConclusionAcupuncture was found to be effective and safe in treating PDC in this study, and the treatment effect lasted up to 4 weeks.Clinical trial registrationhttp://www.chictr.org.cn/index.aspx, identifier ChiCTR2200059979

Cerebral ischemia is one of the leading causes of human mortality and disability worldwide. The treatment of cerebral ischemia is refractory due to its short therapeutic window and lack of effective clinical drugs. Mitophagy, the autophagic elimination of damaged mitochondria, attenuates neuronal injury in cerebral ischemia, indicating the potential of mitophagy inducers as therapies for cerebral ischemia. We previously determined that, by enhancing autophagy flux, the steroidal alkaloid tomatidine can function as a neuroprotective agent against ischemic injury. However, its effects on mitophagy remain unknown. For this purpose, neuroblastoma cell lines Neuro‐2a and SH‐SY5Y were subjected to ischemic injury induced by oxygen–glucose deprivation/reperfusion (OGD/R) and then treated with tomatidine. OGD/R induced a general decrease of cellular contents, and this study revealed that tomatidine had no impact on mitophagy. In addition, tomatidine did not affect mitochondrial contents, including translocase of outer mitochondrial membrane 20 and voltage‐dependent anion channel 1, in either OGD/R‐treated or intact SH‐SY5H cells. Our results indicate that tomatidine exhibits its neuroprotective effects by enhancing autophagy, but in a potentially mitophagy‐independent manner, and provide insights for further investigation into its mechanism(s) and potential therapeutic use against cerebral ischemia.

Abstract Background Adiponectin and zinc alpha2-glycoprotein (ZAG) are associated with frailty. This study aims to further examine the association of adiponectin with ZAG. Methods Outpatients aged 65 years or older with chronic disease followed up in a hospital-based program were recruited for a comprehensive geriatric assessment. We excluded outpatients who were bedridden, residing in a nursing home, with expected life expectancy less than 6 months, or with severe hearing or communication impairment. Plasma ZAG and adiponectin levels were measured. Association between plasma ZAG and adiponectin levels was analyzed by univariate and multivariable linear regression analyses. Results A total of 189 older adults were enrolled (91 men and 98 women, mean age: 77.2 ± 6.1 years). Log-transformed plasma ZAG level was 1.82 ± 0.11 μg/mL, and it was significantly higher in men than that in women (1.85 ± 0.12 vs 1.79 ± 0.10 μg/mL, P = .0006). Log-transformed plasma adiponectin level was 1.00 ± 0.26 μg/mL, and there was no significant gender difference (P = .195). Overall, plasma ZAG level positively correlated with plasma adiponectin level in the multivariable linear regression analysis (P = .0085). The gender-specific significance, however, was less clear: this relationship was significant in men (P = .0049) but not in women (P = .2072). To be more specific by frailty phenotype components, plasma adiponectin was positively correlated with weight loss (P = .0454) and weakness (P = .0451). Conclusions Both of ZAG and adiponectin may be potential frailty biomarkers. Plasma ZAG is an independent factor of plasma adiponectin, especially in older male adults.

Background: Primary intestinal lymphomas (PILs) are rare, and this study compared the clinical outcomes of aggressive primary intestinal B-cell lymphomas (aB-PILs) and T/natural killer-cell lymphomas (T/NK-PILs). Methods: The clinical information of patients diagnosed with aggressive PILs at our institution between 1995 and 2015 were retrospectively investigated. Pathological subtypes were confirmed according to the 2016 revision of the World Health Organization classification. The correlation between clinicopathological features and overall survival (OS) was determined using univariate and multivariate analyses. Results: Cases of T/NK-PILs had higher initial bowel perforation incidence (67% vs. 7%, P

Abstract High temperature causes ubiquitous environmental stress to microorganisms, but studies have not fully explained whether and to what extent heat shock would affect genome stability. Hence, this study explored heat-shock-induced genomic alterations in the yeast Saccharomyces cerevisiae. Using genetic screening systems and customized single nucleotide polymorphism (SNP) microarrays, we found that heat shock (52 °C) for several minutes could heighten mitotic recombination by at least one order of magnitude. More than half of heat-shock-induced mitotic recombinations were likely to be initiated by DNA breaks in the S/G2 phase of the cell cycle. Chromosomal aberration, mainly trisomy, was elevated hundreds of times in heat-shock-treated cells than in untreated cells. Distinct chromosomal instability patterns were also observed between heat-treated and carbendazim-treated yeast cells. Finally, we demonstrated that heat shock stimulates fast phenotypic evolutions (such as tolerance to ethanol, vanillin, fluconazole, and tunicamycin) in the yeast population. This study not only provided novel insights into the effect of temperature fluctuations on genomic integrity but also developed a simple protocol to generate an aneuploidy mutant of yeast.

Morphogen-mediated signaling is critical for proper organ development and stem cell function, and well-characterized mechanisms spatiotemporally limit the expression of ligands, receptors, and ligand-binding cell-surface glypicans. Here, we show that in the developing Drosophila ovary, canonical Wnt signaling promotes the formation of somatic escort cells (ECs) and their protrusions, which establish a physical permeability barrier to define morphogen territories for proper germ cell differentiation. The protrusions shield germ cells from Dpp and Wingless morphogens produced by the germline stem cell (GSC) niche and normally only received by GSCs. Genetic disruption of EC protrusions allows GSC progeny to also receive Dpp and Wingless, which subsequently disrupt germ cell differentiation. Our results reveal a role for canonical Wnt signaling in specifying the ovarian somatic cells necessary for germ cell differentiation. Additionally, we demonstrate the morphogen-limiting function of this physical permeability barrier, which may be a common mechanism in other organs across species.

Background: Readout-segmented echo-planar imaging (rs-EPI) with simultaneous multislice (SMS) technology has been successfully applied to tumor research in many organs, but no feasibility study in rectal cancer has been reported, and the optimal acceleration of SMS with rs-EPI in rectal cancer has not been well determined yet. Objective: To investigate the feasibility of SMS rs-EPI of rectal cancer with different acceleration factors (AFs) and its influence on image quality, acquisition time and apparent diffusion coefficients (ADCs) in comparison to conventional sequences. Methods: All patients underwent rs-EPI and SMS rs-EPI with AFs of 2 and 3 (2 × SMS rs-EPI and 3 × SMS rs-EPI, respectively) using a 3T scanner. Acquisition times of the three rs-EPI sequences were measured. Image qualitative parameters (5-point Likert scale), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), geometric distortion, and apparent diffusion coefficient (ADC) values of the three sequences were compared. Results: A total of eighty-three patients were enrolled in our study. rs-EPI and 2 × SMS rs-EPI offered equivalently high overall image quality with a scan time reduction to nearly half (rs-EPI: 137 s, 2 × SM rs-EPI: 60 s). 3 × SMS rs-EPI showed significantly poorer image quality (p < 0.05). ADC values were significantly lower in 3 × SMS rs-EPI compared to rs-EPI in rectal tumors and normal tissue (tumor tissue: rs-EPI 1.19 ± 0.21 × 10−3 mm2/s, 3 × SMS rs-EPI 1.10 ± 0.26 × 10−3 mm2/s, p < 0.001; normal tissue: rs-EPI 1.68 ± 0.13 × 10−3 mm2/s, 3 × SMS rs-EPI 1.54 ± 0.20 × 10−3 mm2/s, p < 0.001). Conclusions: SMS rs-EPI using an AF of 2 is feasible for rectal MRI resulting in substantial reductions in acquisition time while maintaining diagnostic image quality and similar ADC values to those of rs-EPI when the slice distance and number of shots are the same among three rs-EPI sequences.

Objective: To evaluate the efficacy and safety of preoperative oral gabapentin in preventing postoperative Catheter-Related Bladder Discomfort (CRBD) in surgical patients.Methods: Randomized controlled trials in which gabapentin was used for the prevention of CRBD in surgical patients with transurethral catheterization were evaluated. The primary outcome was the incidence of moderate-to-severe CRBD at 0, 1, 2, and 6 h after surgery, and secondary outcomes included the incidence of any grade CRBD, postoperative pain, and adverse events. Pooled risk ratios (RRs) and mean difference (MD), 95% confidence intervals (CIs), and P values were estimated using fixed and random effects statistical models. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the levels of certainty for key results.Results: A total of 6 randomized controlled trials involving 679 participants were included in the meta-analysis. Gabapentin significantly reduced the risk of moderate-to-severe CRBD at 0, 1, 2, and 6 h (0 h: RR = 0.19, 95% CI: 0.11 to 0.31, p < 0.00001; 1 h: RR = 0.40, 95% CI: 0.25 to 0.66, p < 0.001; 2 h: RR = 0.38, 95% CI: 0.26 to 0.56, p < 0.00001; 6 h: RR = 0.20, 95% CI: 0.11 to 0.38, p < 0.00001). The overall incidence of CRBD at 1 h showed no statistical difference between the two groups (RR = 0.55, 95% CI: 0.30 to 1.00, p = 0.05). The risk of CRBD was significantly reduced in the gabapentin group at 0, 2, and 6 h after surgery (0 h: RR = 0.59, 95% CI: 0.46 to 0.74, p < 0.0001; 2 h: RR = 0.62, 95% CI: 0.51 to 0.75, p < 0.00001; 6 h: RR = 0.66, 95% CI: 0.52 to 0.83, p < 0.001). In addition, gabapentin was associated with low postoperative pain intensity without significant side effects.Conclusion: Preoperative oral gabapentin as an adjunct to surgery is effective in decreasing the risk and severity of CRBD over a short time after surgery, and it can decrease postoperative pain without significant side effects. Overall, the level of certainty was moderate to low.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42021228171.

Considering the characteristics of China's high-speed railway network and the allocation structure of Electric Multiple Units (EMUs), the EMUs operation management mode provides an effective technical route for EMUs route planning optimization. To reduce the number of EMUs, key factors such as the EMUs mileage, time limit, maintenance model, maintenance capability, night accommodation capacity, maintenance management mode, and train tasks are considered as constraints. The number of maintenance tasks is also the objective so that the EMUs route planning solution method is more integrated with actual production needs, and an optimization model of EMUs route planning is established to overcome the shortcomings of previous studies that did not sufficiently consider EMUs maintenance. To verify the feasibility and effectiveness of the proposed model and method of the proposed two-stage optimization algorithm based on column generation, a case study on the preparation of EMUs circulation planning for the Beijing-Shanghai high-speed railway network is conducted, and the results are analyzed.

Background: Double-lumen endotracheal tubes and bronchial blockers are the two lung separation devices most commonly used for lung resection. The preference and outcomes of choosing different lung separation devices have not been discussed in the literature. Methods: This study was conducted using the data of 2 million patients randomly chosen from the National Health Insurance Research Database between 2011 and 2016. We selected patients who underwent lung resection surgery and surveyed their demographic data and trends of double-lumen endotracheal tube and bronchial blocker use. To determine the influence of endotracheal tubes on clinical outcomes, we computed multiple linear regressions of the number of deaths within 30 days after surgery, intensive care unit stay, hospital stay, and medical cost. Results: The use of bronchial blockers in Taiwan has steadily increased from 6.13% to 11.33% from 2011 to 2016. Anaesthesiologists working in regions with higher thoracic surgery volumes preferred bronchial blockers over double-lumen endotracheal tubes. Bronchial blockers were the preferred choice in women, elderly individuals, patients with more comorbidities, and those undergoing video-assisted thoracoscopic surgeries. After adjustment for sex, age, Charlson Comorbidity Index, and video-assisted thoracoscopic surgeries, we found that patients in whom bronchial blockers were applied had shorter hospital stays. Conclusion: The use of bronchial blockers is increasing as the experience of anaesthesiologists increases. Although double-lumen endotracheal tubes remain the principal choice for lung separation in Taiwan, clinical outcomes of the bronchial blocker group were not inferior to those of the double-lumen endotracheal tube group. Keywords: Bronchial blocker, Double-lumen endotracheal tube, Lung separation, Thoracic surgery

Abstract Background Inflammatory bowel disease (IBD) was emerging as a worldwide epidemic disease, and the advanced therapy changed the clinical course and possibly the outcomes. Our previous study reported a higher mortality rate from (IBD) in Taiwan than in Western countries. We proposed to analyze the trend and risk factors of mortality in order to improve the care quality of IBD patients. Methods This retrospective study was conducted to analyze data for January 2001 to December 2015 from a registered database, compiled by the Taiwan’s National Health Insurance. Results Between 2001 and 2015, a total of 3806 IBD patients [Crohn’s disease (CD): 919; ulcerative colitis (UC): 2887] were registered as having catastrophic illness, and 8.2% of these patients died during follow-up. The standardized mortality ratios (SMRs) of CD and UC were 3.72 (95% CI 3.02–4.55) and 1.44 (95% CI 1.26–1.65), respectively, from 2001 to 2015, respectively. A comparison of the periods of 2011–2015 and 2001–2005 revealed a decrease in the mortality rates from both UC and CD. Multivariate Cox proportional hazards analysis identified elderly individuals; sepsis and pneumonia were the risk factors for IBD mortality. The specific risk factors of mortality were liver cancer for UC and surgeries for CD. Conclusion For further decreasing IBD-related mortality in Taiwan, we need to pay special attention toward elderly individuals, infection control, cancer screening and improvement in perioperative care.

Abstract Background Colorectal cancer (CRC) is one of the most common cancers worldwide. Screening for CRC using the fecal occult blood test (FOBT) is feasible and useful for decreasing disease‐related mortality; however, its sensitivity and compliance are unsatisfactory. Methods This study examined the efficacy of using serum placenta growth factor (PlGF) for a novel CRC screening strategy. To investigate a potential novel screening tool for CRC, we compared the sensitivity, specificity, positive predictive value, and negative predictive value of the FOBT, serum PlGF, and their combination through an examination of two independent cohorts and validation using the second cohort. All the patients and control group received the colonoscopy and FOBT, the colonoscopy was used as the gold standard for the result. Results Serum PlGF levels were significantly increased in CRC patients (16.8 ± 11.4 pg/mL) compared with controls (12.0 ± 11.2 pg/mL). The predictive model that used the serum PlGF level alone was as effective as the FOBT (AUC: 0.60 vs 0.68, P = 0.891), and it had significantly higher sensitivity than the FOBT (0.81 vs 0.39). In addition, we found serum PlGF level has a good value for predicting CRC patients in those FOBT negative populations. Finally, combining serum PlGF level and the FOBT improved the predictive power and demonstrated satisfactory sensitivity (0.71) and specificity (0.71). This result was confirmed and validated in the second independent cohort. Furthermore, no matter the stages (early/advanced) and the location (distal/proximal) of CRC, the efficacy of serum PlGF and the combined model remained quite stable. Conclusion Serum PlGF level is a potential alternative screening tool for CRC, especially for those who are reluctant to stool‐based screening methods and who were tested as negative FOBT. In addition, combining serum PlGF level and the FOBT could increase the power of CRC screening.

Abstract Background Methanol poisoning is a serious public health issue in developing countries, but few data are available in the literature on acute kidney injury (AKI) after methanol intoxication. Methods This study examined the clinical features, spectrum and outcomes of AKI in patients with methanol intoxication and evaluated the predictors of mortality after methanol intoxication. A total of 50 patients with methanol intoxication were seen at Chang Gung Memorial Hospital between 2000 and 2013. Patients were grouped according to the status of renal damage as AKI (n = 33) or non-AKI (n = 19). Demographic, clinical, laboratory, and mortality data were obtained for analysis. Results Most patients were middle-aged (47.8 ± 14.9 years), predominantly male (74.0%), and habitual alcohol consumers (70.0%). Most incidents were oral exposures (96.0%) and unintentional (66.0%). Two (4.0%) patients attempted suicide by intravenous injection of methanol. Five (10.0%) patients suffered methanol intoxication after ingestion of methomyl pesticide that contained methanol as a solvent. Compared to non-AKI patients, the AKI patients were older (50.9 ± 13.7 versus 41.6 ± 15.6 years, P = 0.034), predominantly male (90.9% versus 42.8%, P = 0.000), more habitual alcohol users (84.8% versus 41.2%, P = 0.001) and had more unintentional exposures (82.8% versus 35.3%, P = 0.001). Furthermore, there was a higher incidence of respiratory failure (63.6% versus 29.4%, P = 0.022) in the AKI group than in the non-AKI group, respectively. The laboratory studies revealed that the AKI patients suffered from more severe metabolic acidosis than the non-AKI patients. By the end of this study, 13 (39.5%) AKI patients and 1 (5.9%) non-AKI patient had died. The overall in-hospital hospital mortality rate was 28%. In a multivariate binary logistic regression model, it was demonstrated that AKI (odds ratio 19.670, confidence interval 1.026–377.008, P = 0.048) and Glasgow coma scale score (odds ratio 1.370, confidence interval 1.079–1.739, P = 0.010) were significant factors associated with mortality. The Kaplan-Meier analysis disclosed that AKI patients suffered lower cumulative survival than non-AKI patients (log-rank test, chi-square = 5.115, P = 0.024). Conclusions AKI was common (66.0%) after methanol intoxication and was predictive of in-hospital hospital mortality. The development of AKI was associated with a 19.670-fold higher risk of in-hospital mortality.

An aerobic bacterium, designated as strain KD337-16T, was isolated from the fecal samples of a black pig. It exhibited spherical, non-motile and non–spore-forming, Gram-positive cells. KD337-16T was identified as a member of the genus Micrococcus through 16S rRNA gene sequencing, and its closest relatives were found to be Micrococcus endophyticus YIM 56238T (99.5% similarity), Micrococcus luteus NCTC 2665T (99.1%), Micrococcus yunnanensis YIM 65004T (99.1%), Micrococcus aloeverae AE-6T (99.1%), Micrococcus antarcticus T2T (98.9%), and Micrococcus flavus LW4T (98.7%). Phylogenomic trees were constructed, and strain KD337-16T was found to form its own cluster as an independent lineage of M. flavus LW4T. Between KD337-16T and its close relatives, the average nucleotide identity, average amino acid identity, and digital DNA–DNA hybridization were below the respective species delineation thresholds at 82.1–86.6%, 78.1–86.1%, and 24.4–34.9%. The major cellular fatty acids and polar lipids were anteiso-C15:0 and iso-C15:0, and DPG and PG, respectively. The predominant menaquinone was MK-8(H2). Taken together, the results indicate that strain KD337-16T is a novel species of the genus Micrococcus, for which the name Micrococcus porci sp. nov. is proposed. The type strain is KD337-16T (=BCRC 81318T = NBRC 115578T).

Introduction Hangeshashinto has been employed for oral mucositis prevention in patients receiving cancer treatment, but the evidence has not been sufficiently robust to guide clinical decision-making. This study will therefore be undertaken to assess the effectiveness of Hangeshashinto for preventing oral mucositis in patients with cancer who are receiving treatment.Methods and analysis The databases will include PubMed, Embase, the Cochrane Library, Chinese databases and Japanese databases. The literature will be searched from the databases’ inception until May 2021. Other sources, such as potential grey literature, reference lists from included studies and relevant systematic reviews and conference papers, will also be searched. The primary outcome is the incidence of mucositis of any severity, and the secondary outcomes are interruptions to cancer treatment, oral pain and nutritional status. The risk of bias of eligible studies will be assessed using the Cochrane Collaboration’s ‘risk of bias’ tool. Both the Q test and I2 statistic will be performed to assess statistical heterogeneity. If I2 >50%, sensitivity and subgroup analysis will be conducted. The quality of evidence will be rated according to the Grading of Recommendations, Assessment, Development and Evaluation approach. Egger’s test will be used to assess reporting bias.Ethics and dissemination This systematic review will evaluate only published data; therefore, ethical approval is not required.PROSPERO registration number CRD42020216145.

Three films of Ni with thicknesses of 100, 300, and 500 ​nm were deposited on an Al2O3 base and direct bonded with Al to form high-power electronic substrates for comparison. The microstructures of Al/Al2O3 joints were evaluated using a scanning electron microscope (SEM) and transmission electron microscope (TEM) equipped with an energy dispersive spectrometer. No reaction layer was found at the interface between Al and Al2O3, and the Ni film dissolved in the Al foil and reacted with Al to form a eutectic liquid phase near the interface to wet and join with the Al2O3 base. An Al3Ni intermetallic compound was formed in the Al substrate because of Ni precipitation, which reacted with Al at its grain boundaries. The bonding area percentage, shear strength, and thermal conductivity for Al and Al2O3 were evaluated using scanning acoustic tomography (SAT), ISO 13124 shear strength test, and the laser flash method, respectively. The Al/Al2O3 specimen deposited with the 500-nm Ni film had the highest shear strength (31.5 ​MPa), thermal conductivity (37.8 ​W/mK), and bonding area percentage (~99.68%).

Background/Aims Incidences of inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn’s disease (CD), have been increasing in Asia. In this study, we report the relevant clinical characteristics and determined the epidemiological trend of IBD in Taiwan from 2001 to 2015. Methods A retrospective study was conducted to analyze data recorded from January 2001 through December 2015 in the registered database compiled by the National Health Insurance and provided by the Ministry of Health and Welfare, Taiwan. Results A total of 3,806 patients with catastrophic IBD illness were registered from 2001 to 2015 in Taiwan (CD, 919; UC, 2,887). The crude incidence of CD increased from 0.17/100,000 in 2001 to 0.47/100,000 in 2015, whereas that of UC increased from 0.54/100,000 in 2001 to 0.95/100,000 in 2015. The prevalence of CD increased from 0.6/100,000 in 2001 to 3.9/100,000 in 2015, whereas that of UC increased from 2.1/100,000 in 2001 to 12.8/100,000 in 2015. The male-to-female ratio in the study sample was 2.19 for CD and 1.62 for UC. The median age of those registered with CD was lower than that of those registered for UC: 38.86 and 44.86 years, respectively. A significantly greater increase in CD incidence rate was identified among 20 to 39-year-old compared with other age groups. Conclusions Using Taiwan’s nationwide insurance database, we determined that the number of patients with CD increased more rapidly during the study period than the number of patients with UC, especially among age 20 to 39-year-old, resulting in a decreased UC-to-CD ratio.

Nowadays, Over-The-Top (OTT) voice call service has become more popular than other Voice over Internet Protocol services provided by mobile operators due to cheaper costs. For devices with more than one network interfaces, the OTT software may need to handover between heterogeneous networks during a call. Unnecessary handover may lead to signal overload, especially in a Wi-Fi intensive area where users may handover frequently between Wi-Fi and cellular networks. For example, if the period between when a user handovers from Wi-Fi to Long Term Evolution (LTE) and when the user handovers from LTE back to Wi-Fi is too short to transmit voice data, the handover procedures between Wi-Fi and LTE can be considered unnecessary and power consuming. To tackle this issue, this paper proposes delay handover mechanism (DHM) to avoid the unnecessary handover procedures by postponing the timing to handover from Wi-Fi to LTE. We then propose an analytical model as well as a simulation model to investigate how many handovers can be reduced. The analytical model is validated against the simulation model. With extensive simulation experiments, the performance evaluation of DHM offers a guideline to configure parameters based on the trade-off between reduced handover ratio and packet loss rate. As a whole, DHM is an application-based mechanism for avoiding unnecessary handovers as well as cutting down LTE usages.

An accurate and effective neurological evaluation is indispensable in the treatment and rehabilitation of traumatic brain injury. However, most of the existing evaluation methods in basic research and clinical practice are not objective or intuitive for assessing the neurological function of big animals, and are also difficult to use to qualify the extent of damage and recovery. In the present study, we established a big animal model of traumatic brain injury by impacting the cortical motor region of beagles. At 2 weeks after successful modeling, we detected neurological deficiencies in the animal model using a series of techniques, including three-dimensional motion capture, electromyogram and ground reaction force. These novel technologies may play an increasingly important role in the field of traumatic brain injury diagnosis and rehabilitation in the future. The experimental protocol was approved by the Animal Care and Use Committee of Logistics University of People’s Armed Police Force (approval No. 2017-0006.2).

Abstract In a perturbative QCD approach we study the direct CP violation in the pure annihilation decay process of $$\bar{B}^0_{s}\rightarrow \pi ^+\pi ^-\pi ^+\pi ^-$$ B ¯ s 0 → π + π - π + π - induced by the $$\rho $$ ρ and $$\omega $$ ω double resonance effect. Generally, the CP violation is small in the pure annihilation type decay process. However, we find that the CP violation can be enhanced by double $$\rho $$ ρ – $$\omega $$ ω interference when the invariant masses of the $$\pi ^+\pi ^-$$ π + π - pairs are in the vicinity of the $$\omega $$ ω resonance. For the decay process of $$\bar{B}^0_{s}\rightarrow \pi ^+\pi ^-\pi ^+\pi ^-$$ B ¯ s 0 → π + π - π + π - , the CP violation can reach $$A_{CP}(\bar{B}^0_{s}\rightarrow \pi ^+\pi ^-\pi ^+\pi ^-)=27.20^{+0.05+0.28+7.13}_{-0.15-0.31-6.11}\%$$ A C P ( B ¯ s 0 → π + π - π + π - ) = 27 . 20 - 0.15 - 0.31 - 6.11 + 0.05 + 0.28 + 7.13 % .

This paper reports the syntheses, crystal structures and magnetic properties of Mn(III) hexadentate Schiff base complexes [Mn(4-OH-sal-N-1,5,8,12)]NO3(1) and [Mn(4-OH-sal-N-1,5,8,12)]ClO4(2), where (4-OH-sal-N-1,5,8,12)2− (4,4′-((1E,13E)-2,6,9,13-tetraazatetradeca-1,13-diene-1,14-diyl)bis(3-methoxyphenol) is a new hydroxyl-substituted hexadentate Schiff base ligand. The introduction of the (4-OH-sal-N-1,5,8,12)2− ligand induces more hydrogen bonding interactions, in addition to promoting the formation of intermolecular interactions among the cations. However, the close-packing structures of both complexes lead to their stabilization in the high-spin state in the temperature range of 2−300 K.

Necrostatin-1 (Nec-1) is a specific small molecule inhibitor of receptor-interacting protein kinase 1 (RIPK1) that specifically inhibits phosphorylation of RIPK1. RIPK1 regulates inflammation and cell death by interacting with receptor-interacting serine/threonine protein kinases 3(RIPK3). We hypothesized that Nec-1 may have anti-inflammatory efficacy in patients with osteoarthritis (OA), as the pathophysiology of OA involves the activation of inflammation-related signaling pathways and apoptosis. In this study, we explored the effects of Nec-1 on interleukin (IL)-1β-induced inflammation in mouse chondrocytes and the destabilised medial meniscus (DMM) mouse model. Inhibiting RIPK1 with Nec-1 dramatically suppressed catabolism both in vivo and in vitro, but did not inhibit changes in subchondral bone. Nec-1 abolished the in vitro increases in matrix metalloproteinase (MMP) and ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTs5) expression induced by IL-1β. However, adding high-mobility group box 1 (HMGB1) partially abrogated this effect, indicating the essential role of HMGB1 and Nec-1 in the protection of primary chondrocytes. Furthermore, Nec-1 decreased the expression of Toll-like receptor 4 (TLR4) and stromal cell-derived factor-1 (SDF-1), and attenuated the interaction between TLR4 and HMGB1. Western blot results suggested that Nec-1 significantly suppressed IL-1β-induced NF-κB transcriptional activity, but not MAPK pathway. Micro-computed tomography, immunohistochemical staining, and Safranin O/Fast Green staining were used in vivo to assess the degree of destruction of OA cartilage. The results show that NEC-1 can significantly reduce the degree of destruction of OA cartilage. Therefore, Nec-1 may be a novel therapeutic candidate to treat OA.

Osteoporosis is an enormous health problem caused by the imbalance between bone resorption and bone formation. The current therapeutic strategies for osteoporosis still have some limitations. Boldine, an alkaloid isolated from Peumus boldus, has been shown to have antioxidant and anti-inflammatory effects in vivo. For the first time, we discover that boldine has a protective effect for the estrogen deficiency-induced bone loss in mice. According to the Micro-CT and histomorphometry assays, boldine conducts this protective effect through inhibiting bone resorption without affecting bone formation in vivo. Moreover, we showed that boldine can inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation via impairing the AKT signaling pathways, while SC79 (an AKT agonist) partially rescue this effect. In conclusion, our results suggest that boldine can prevent estrogen deficiency-induced osteoporosis by inhibiting osteoclastogenesis. Thus, boldine may be served as a novel therapeutic agent for anti-osteoporotic therapy.

Ensuring an acceptable level of edible agro-products quality and safety is necessary to provide adequate protection for consumers. It is the first time that we analyzed the edible agro-products quality and safety issues in the supply chain, including production, processing, circulation, and consumption. The results indicate that the agro-products quality and safety levels improves steadily, and the supervision system and standardization system are both enhanced significantly, however, certain challenges still remain in each stage of the supply chain and the entire supervision process. Finally, five recommendations regarding four aspects (production, processing, circulation, and consumption) are concluded.