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Zhi-Bin Kong,1 Xing-De Wang,2 Shu-Rong Shen,2 Hua Liu,1 Li Zhou,2 Bin Chen,2 Zhong Chen,2 Shao-Jun Yin1 1Department of Respiratory Medicine, Shanghai Sixth People’s Hospital East Affiliated to Shanghai University of Medicine and Health Science, Shanghai 201306, People’s Republic of China; 2Department of Cardiology, Shanghai Sixth People’s Hospital East Affiliated to Shanghai University of Medicine and Health Science, Shanghai 201306, People’s Republic of ChinaCorrespondence: Xing-De WangDepartment of Cardiology, Shanghai Sixth People’s Hospital East Affiliated to Shanghai University of Medicine and Health Science, No. 222 Huanhu West Road, Lingang New City, Pudong New Area, Shanghai 201306, People’s Republic of ChinaTel +862138297277Email sd_wangxd@sumhs.edu.cnShao-Jun YinDepartment of Respiratory Medicine, Shanghai Sixth People’s Hospital East Affiliated to Shanghai University of Medicine and Health Science, No. 222 Huanhu West Road, Lingang New City, Pudong New Area, Shanghai 201306, People’s Republic of ChinaTel +862138297762Email yinshaojun2010@163.comPurpose: Chronic obstructive pulmonary disease (COPD) is associated with increased incidence of arrhythmias, which has been attributed to autonomic dysregulation. Detection of autonomic function may facilitate stratification of COPD patients with respect to their risk of development of arrhythmias.Patients and Methods: A total of 151 COPD patients and 45 non-COPD patients were included in this study. Heart rate deceleration runs (DRs) were detected by dynamic electrocardiogram (ECG); DRs successively occurring in 2, 4, or 8 cardiac cycles were denoted as DR2, DR4, and DR8, respectively. Indicators of arrhythmias including isolated premature atrial contractions (PAC), supraventricular tachycardia (SVT), isolated premature ventricular contractions (PVC), and ventricular tachycardia (VT) were recorded. Occurrence of SVT or PAC ≥ 70/day was considered positive for supraventricular arrhythmias, while positive ventricular arrhythmias category (PVAC) was defined as occurrence of VT or PVC ≥ 10/hour.Results: Compared with non-COPD individuals, COPD patients were associated with increased number of PAC, PVC, higher incidence of PAC > 70/d, SVT, PVAC, and decreased DRs (DR2, DR4, DR8) (P< 0.05). In COPD patients, DRs showed a negative correlation with the incidence of PAC, PVC, SVT, and PVAC (P< 0.05). In receiver operating characteristic curve analysis, all the DRs were found to be significant predictors of PAC > 70/d, SVT, and PVAC. The predictive power of DRs was significantly different from one another with the order ranged as DR4>DR8>DR2 for PAC > 70/d, DR8>DR4>DR2 for SVT, and DR8>DR4>DR2 for PVAC.Conclusion: Our study provides evidence of significant autonomic dysregulation in COPD patients. DRs may serve as a marker of the risk of arrhythmias in COPD patients.Keywords: chronic obstructive pulmonary disease, arrhythmias, deceleration capacity runs, autonomic function, risk stratification

Kv1.3 belongs to the voltage-gated potassium (Kv) channel family, which is widely expressed in the central nervous system and associated with a variety of neuropsychiatric disorders. Kv1.3 is highly expressed in the olfactory bulb and piriform cortex and involved in the process of odor perception and nutrient metabolism in animals. Previous studies have explored the function of Kv1.3 in olfactory bulb, while the role of Kv1.3 in piriform cortex was less known. In this study, we investigated the neuronal changes of piriform cortex and feeding behavior after smell stimulation, thus revealing a link between the olfactory sensation and body weight in Kv1.3 KO mice. Coronal slices including the anterior piriform cortex were prepared, whole-cell recording and Ca 2+ imaging of pyramidal neurons were conducted. We showed that the firing frequency evoked by depolarization pulses and Ca 2+ influx evoked by high K + solution were significantly increased in pyramidal neurons of Kv1.3 knockout (KO) mice compared to WT mice. Western blotting and immunofluorescence analyses revealed that the downstream signaling molecules CaMKII and PKCα were activated in piriform cortex of Kv1.3 KO mice. Pyramidal neurons in Kv1.3 KO mice exhibited significantly reduced paired-pulse ratio and increased presynaptic Cav2.1 expression, proving that the presynaptic vesicle release might be elevated by Ca 2+ influx. Using Golgi staining, we found significantly increased dendritic spine density of pyramidal neurons in Kv1.3 KO mice, supporting the stronger postsynaptic responses in these neurons. In olfactory recognition and feeding behavior tests, we showed that Kv1.3 conditional knockout or cannula injection of 5-(4-phenoxybutoxy) psoralen, a Kv1.3 channel blocker, in piriform cortex both elevated the olfactory recognition index and altered the feeding behavior in mice. In summary, Kv1.3 is a key molecule in regulating neuronal activity of the piriform cortex, which may lay a foundation for the treatment of diseases related to piriform cortex and olfactory detection., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Previous studies found that histamine H2 receptor antagonists (H2RAs) had blood pressure lowering and cardioprotective effects, but the impact of H2RAs on the survival outcomes of critically ill patients with essential hypertension is still unclear. The aim of this study was to investigate the association of H2RAs exposure with all-cause mortality in patients with essential hypertension based on Medical Information Mart for Intensive Care III database. A total of 17,739 patients were included, involving 8482 H2RAs users and 9257 non-H2RAs users. Propensity score matching (PSM) was performed to improve balance between 2 groups that were exposed to H2RAs or not. Kaplan-Meier survival curves were used to compare the cumulative survival rates and multivariable Cox regression models were performed to evaluate the association between H2RAs exposure and all-cause mortality. After 1:1 PSM, 4416 pairs of patients were enrolled. The results revealed potentially significant association between H2RAs exposure and decreased 30-day, 90-day, and 1-year mortalities in multivariate analyses (HR = 0.783, 95% CI: 0.696-0.882 for 30-day; HR = 0.860, 95% CI: 0.778-0.950 for 90-day; and HR = 0.883, 95% CI: 0.811-0.961 for 1-year mortality, respectively). Covariate effect analyses showed that the use of H2RAs was more beneficial in essential hypertension patients with age ≥ 60, BMI ≥ 25 kg/m 2 , coronary arteriosclerosis, stroke, and acute kidney failure, respectively. In conclusion, H2RAs exposure was related to lower mortalities in critically ill patients with essential hypertension, which provided novel potential strategy for the use of H2RAs in essential hypertension patients., (© 2024, The American College of Clinical Pharmacology.)

Background: Severe heart failure (HF) has a higher mortality during vulnerable period while targeted predictive tools, especially based on drug exposures, to accurately assess its prognoses remain largely unexplored. Therefore, this study aimed to utilize drug information as the main predictor to develop and validate survival models for severe HF patients during this period., Methods: We extracted severe HF patients from the MIMIC-IV database (as training and internal validation cohorts) as well as from the MIMIC-III database and local hospital (as external validation cohorts). Three algorithms, including Cox proportional hazards model (CoxPH), random survival forest (RSF), and deep learning survival prediction (DeepSurv), were applied to incorporate the parameters (partial hospitalization information and exposure durations of drugs) for constructing survival prediction models. The model performance was assessed mainly using area under the receiver operator characteristic curve (AUC), brier score (BS), and decision curve analysis (DCA). The model interpretability was determined by the permutation importance and Shapley additive explanations values., Results: A total of 11,590 patients were included in this study. Among the 3 models, the CoxPH model ultimately included 10 variables, while RSF and DeepSurv models incorporated 24 variables, respectively. All of the 3 models achieved respectable performance metrics while the DeepSurv model exhibited the highest AUC values and relatively lower BS among these models. The DCA also verified that the DeepSurv model had the best clinical practicality., Conclusions: The survival prediction tools established in this study can be applied to severe HF patients during vulnerable period by mainly inputting drug treatment duration, thus contributing to optimal clinical decisions prospectively., (© 2024. The Author(s).)

Purpose: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV)., Methods: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients., Results: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020-1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not., Conclusion: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To observe the therapeutic effect of transcutaneous electrical acupoint stimulation (TEAS) based on the theory of " qi ascending and descending movement" in patients after general anesthesia laparoscopic cholecystectomy, so as to explore the impact of TEAS on the autonomic nervous system and gastrointestinal function of patients., Methods: A total of 204 patients scheduled to undergo general anesthesia laparoscopic cholecystectomy were selected and randomly divided into control, double acupoints and multiple acupoints groups, with 68 cases in each group. For patients in the multiple acupoints group, TEAS was applied at Zusanli (ST36), Tiantu (CV22), Danzhong (CV17), Zhongwan (CV12), Taichong (LR3), and Neiguan (PC6) 30 min before anesthesia induction until the end of the surgery. In the double acupoints group, TEAS was applied only at ST36 and PC6. No electrical stimulation was applied in the control group. The postoperative bloating, bowel sound recovery time, first farting time, first defecation time, length of hospital stay, nausea and vomiting were compared among the three groups. Heart rate variability was monitored by twelve-lead electrocardiogram to evaluate the autonomic nervous function of the patients, including the low frequency power/high frequency power ratio (LF/HF), the standard deviation of all sinus RR intervals (SDNN), and the root mean square of difference between successive normal RR intervals (RMSSD)., Results: At 6 h and 24 h after surgery, the symptoms of bloating, nausea and vomiting in the multiple acupoints group and double acupoints group were significantly improved compared to the control group ( P <0.05), and the multiple acupoints group was superior to the double acupoints group ( P <0.05). Compared with the control group, the bowel sound recovery time, first farting time, first defecation time, and length of hospital stay were significantly shorter ( P <0.05) in the multiple acupoints group and double acupoints group, and the multiple acupoints group was superior to the double acupoints group ( P <0.05). At 1 d and 2 d after surgery, compared with the control group, LF/HF was decreased ( P <0.05) while SDNN and RMSSD were increased ( P <0.05) in the multiple acupoints group and double acupoints group, and there was a significant difference between the two groups ( P <0.05)., Conclusions: TEAS treatment based on the theory of " qi ascending and descending movement" can relieve gastrointestinal dysfunction, reduce early postoperative sympathetic nerve excitement and maintain parasympathetic nerve tension in patients after general anesthesia laparoscopic cholecystectomy, thereby promoting gastrointestinal function recovery.

Based on the one-year observational data of volatile organic compounds （VOCs） in an urban area of Yuncheng in 2021， the concentration， composition， sources， and ozone-sensitive species of VOCs in four seasons were analyzed. The results showed that the average annual concentration of VOCs was （32.1 ±24.2）×10 -9 ， i.e.， at the national middle level. The seasonal concentrations of VOCs were in the order of： winter （46.3×10 -9 ）&gt; autumn （35.5×10 -9 ）&gt; spring （25.6×10 -9 ）&gt; summer （21.2×10 -9 ）. Alkanes and OVOCs were the most dominant VOCs compounds， accounting for 69.0%-80.4% of TVOCs in Yuncheng. Affected by changes in source emissions， the proportion of OVOCs was higher in spring and summer （41%-43%）， whereas the proportion of alkanes was higher in autumn and winter （42%-43%）. Vehicle exhaust， LPG/NG， industrial production， and combustion sources were identified as the main sources of VOCs in Yuncheng. The largest contributors in the four seasons were vehicle exhaust （28.5% in spring）， secondary + combustion sources （29.0% in summer）， LPG/NG sources （30.4% in autumn）， and coal combustion （27.3% in winter）. The ozone formation was located in the transitional regime in summer and in the VOC-limited regime in other seasons. Ozone production was more sensitive to alkenes （isoprene， ethylene， and propene）， OVOCs （acetaldehyde and propanal）， and aromatics （xylene， toluene， and benzene）. Winter was more sensitive to ethylene， and the other seasons were more sensitive to isoprene. The primary emission sources related to these sensitive species should be reduced to achieve the goal of air quality improvement.

To investigate the mechanism of Wenshen Xuanbi Decoction (WSXB) in treating osteoarthritis (OA) via network pharmacology, bioinformatics analysis, and experimental verification. The active components and prediction targets of WSXB were obtained from the TCMSP database and Swiss Target Prediction website, respectively. OA-related genes were retrieved from GeneCards and OMIM databases. Protein-protein interaction and functional enrichment analyses were performed, resulting in the construction of the Herb-Component-Target network. In addition, differential genes of OA were obtained from the GEO database to verify the potential mechanism of WSXB in OA treatment. Subsequently, potential active components were subjected to molecular verification with the hub targets. Finally, we selected the most crucial hub targets and pathways for experimental verification in vitro. The active components in the study included quercetin, linolenic acid, methyl linoleate, isobergapten, and beta-sitosterol. AKT1, tumor necrosis factor (TNF), interleukin (IL)-6, GAPDH, and CTNNB1 were identified as the most crucial hub targets. Molecular docking revealed that the active components and hub targets exhibited strong binding energy. Experimental verification demonstrated that the mRNA and protein expression levels of IL-6, IL-17, and TNF in the WSXB group were lower than those in the KOA group (p < 0.05). WSXB exhibits a chondroprotective effect on OA and delays disease progression. The mechanism is potentially related to the suppression of IL-17 and TNF signaling pathways and the down-regulation of IL-6.

Due to its clinical and cosmetic applications, investigators have paid attention to tyrosinase (TYR) inhibitor development. In this study, a TYR inhibition study with acarbose was investigated to gain insights into the regulation of the catalytic function. Biochemical assay results indicated that acarbose was turned to be an inhibitor of TYR in a reversible binding manner and probed as a distinctive mixed-type inhibitor via measurement of double-reciprocal kinetic ( K i = 18.70 ± 4.12 mM). Time-interval kinetic measurement indicated that TYR catalytic function was gradually inactivated by acarbose in a time-dependent behavior displaying with a monophase process that was evaluated by semi-logarithmic plotting. Spectrofluorimetric measurement by integrating with a hydrophobic residue detector (1-anilinonaphthalene-8-sulfonate) showed that the high dose of acarbose derived a conspicuous local structural deformation of the TYR catalytic site pocket. Computational docking simulation showed that acarbose bound to key residues such as HIS61, TYR65, ASN81, HIS244, and HIS259. Our study extends an understanding of the functional application of acarbose and proposes that acarbose is an alternative candidate drug for a whitening agent via direct retardation of TYR catalytic function and it would be applicable for the relevant skin hyperpigmentation disorders concerning the dermatologic clinical purpose.Communicated by Ramaswamy H. Sarma.

Purpose: To investigate the association between proton pump inhibitors (PPIs) administration during hospitalization and mortality and length of stay in critically ill pediatric patients., Materials and Methods: This is a retrospective observational cohort study on pediatric ICU patients (0 to 18 years). Propensity score matching (PSM), Kaplan-Meier curves, Cox proportional hazards model and Linear regression model was applied for assessing the effects of PPIs on mortality and other outcomes during hospitalization., Results: A total of 2269 pediatric ICU patients were included, involving 1378 omeprazole (OME) users and 891 non-OME users. The results showed significant association between OME exposure and decreased ICU stay (β -0.042; 95% CI -0.073--0.011; P = 0.008) but prolonged non-ICU hospital stay (β 0.121; 95% CI 0.097-0.155; P = 0.040). No statistical significance was observed between OME exposure and reduced mortality, but the OME group had a slightly decreased tendency in 28-day mortality (HR 0.701; 95% CI 0.418-1.176) and in-hospital mortality (HR 0.726; 95% CI 0.419-1.257). Furthermore, subgroup analyses revealed that the decreased tendency of mortality were more obvious in patients less than 1 year old compared with older pediatric patients, although not statistically significant. In addition, we also observed that OME exposure was significantly associated with reduced mortality of general ICU subgroup., Conclusions: This study provided a sign that PPIs used only in the ICU, rather than throughout hospital stay, might provide more benefit for critically ill pediatric patients. Additionally, younger pediatric patients might gain relatively more benefit than older children when receiving PPIs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Our previous study reported that histamine H2 receptor antagonists (H2RAs) exposure was associated with decreased mortality in critically ill patients with heart failure (HF) through the same pharmacological mechanism as β-blockers. However, population-based clinical study directly comparing the efficacy of H2RAs and β-blockers on mortality of HF patients are still lacking. This study aims to compare the association difference of H2RAs and β-blockers on mortality in critically ill patients with HF using the Medical Information Mart for Intensive Care III database (MIMIC-III). Methods: Study population was divided into 4 groups: β-blockers + H2RAs group, β-blockers group, H2RAs group, and Non-β-blockers + Non-H2RAs group. Kaplan-Meier curves and multivariable Cox regression models were employed to evaluate the differences of all-cause mortalities among the 4 groups. Propensity score matching (PSM) was used to increase comparability of four groups. Results: A total of 5593 patients were included. After PSM, multivariate analyses showed that patients in H2RAs group had close all-cause mortality with patients in β-blockers group. Furthermore, 30-day, 1-year, 5-year and 10-year all-mortality of patients in β-blockers + H2RAs group were significantly lower than those of patients in β-blockers group, respectively (HR: 0.64, 95%CI: 0.50-0.82 for 30-day; HR: 0.80, 95%CI: 0.69-0.93 for 1-year mortality; HR: 0.83, 95%CI: 0.74-0.93 for 5-year mortality; and HR: 0.85, 95%CI: 0.76-0.94 for 10-year mortality, respectively). Conclusion: H2RAs exposure exhibited comparable all-cause mortality-decreasing effect as β-blockers; and, furthermore, H2RAs and β-blockers had additive or synergistic interactions to improve survival in critically ill patients with HF., 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., (Copyright © 2023 Zhang, Cai, Wang, Xu, Yin, Huang, Guo, Jiang, Pan, Li and He.)

Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare no competing financial interests.

Background: Recently, increasing evidence has demonstrated that IL-10 single nucleotide polymorphisms (SNPs) are associated with the risk of acute leukemia (AL), but the findings of different articles remain controversial. Thus, we performed a meta-analysis to further investigate the exact roles of IL-10 SNPs in AL susceptibility., Methods: Six common Chinese and English databases were utilized to retrieve eligible studies. The strength of the association was assessed by calculating odds ratios and 95 % confidence intervals. All analyses were carried out using Review Manager (version 5.3) and STATA (version 15.1). The registered number of this research is CRD42022373362., Results: A total of 6391 participants were enrolled in this research. The results showed that the AG genotype of rs1800896 increased AL risk in the heterozygous codominant model (AG vs. AA, OR = 1.41, 95 % CI = 1.04-1.92, P = 0.03) and overdominant model (AG vs. AA + GG, OR = 1.32, 95 % CI = 1.04-1.70, P = 0.03). In the subgroup analysis, associations between the G allele, GG genotype, AG genotype, AG + GG genotype of rs1800896 and increased AL risk were also observed in the mixed population based on allelic, homozygote codominant, heterozygous codominant, dominant, and overdominant models. Furthermore, an association between the AC genotype of rs1800872 and increased AL risk was observed in the Caucasian population in the overdominant model. However, the rs1800871, rs3024489 and rs3024493 polymorphisms did not affect AL risk., Conclusion: IL-10 rs1800896 and rs1800872 affected the susceptibility of AL and therefore may be biomarkers for early screening and risk prediction of AL., 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 Ltd. All rights reserved.)

A core-shell-derived structural magnetic zeolite imidazolate framework-67 (Fe 3 O 4 -COOH@ZIF-67) nanocomposite was fabricated through a single-step coating of zeolite imidazolate framework-67 on glutaric anhydride-functionalized Fe 3 O 4 nanosphere for the magnetic solid-phase extraction (MSPE) of theophylline (TP). The Fe 3 O 4 -COOH@ZIF-67 nanocomposite was characterized through scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectrometry, Fourier transform infrared spectroscopy, Zeta potential analysis, X-ray diffraction, Brunauer-Emmett-Teller, and vibrating sample magnetometer. The material has a high specific surface area and good magnetism, which maintains the regular dodecahedron structure of ZIF-67 without being destroyed by the addition of Fe 3 O 4 -COOH nanospheres. The Fe 3 O 4 -COOH@ZIF-67 can rapidly adsorb TP mainly through the strong coordination interaction between undercoordinated Co 2+ on ZIF-67 and -NH from imidazole of TP. The adsorption and desorption conditions, such as the amount of adsorbent, adsorption time, pH value, and elution solvent, were optimized. The kinetics of TP adsorption on Fe 3 O 4 -COOH@ZIF-67 was found to follow pseudo-second-order kinetics. The Langmuir model fits the adsorption data well and the maximum adsorption capacity is 1764 mg/g. Finally, the developed MSPE-HPLC method was applied in the enrichment and analysis of TP in four tea samples and rabbit plasma. TP was not detected in oolong tea and rabbit plasma, and its contents in jasmine tea, black tea, and green tea are 5.80, 4.31, and 1.53 μg/g, respectively. The recoveries of spiked samples are between 74.41% and 86.07% with RSD in the range of 0.81-3.83%. The adsorption performance of Fe 3 O 4 -COOH@ZIF-67 nanocomposite was nearly unchanged after being stored at room temperature for at least 80 days and two consecutive adsorption-desorption cycles. The results demonstrate that Fe 3 O 4 -COOH@ZIF-67 nanocomposite is a promising magnetic adsorbent for the preconcentration of TP in complex samples.

Euphausia superba (Antarctic krill) serine protease (ESP) was investigated to gain insights into the activity-structural relationship, folding behavior, and regulation of the catalytic function. We purified ESP from the krill muscle and characterized biochemical distinctions via enzyme kinetics. Studies of inhibition kinetics and unfolding in the presence of a serine residue modifier, such as phenylmethanesulfonyl fluoride, were conducted. Structural characterizations were measured by spectrofluorimetry, including 1-anilinonaphthalene-8-sulfonate dye labeling for hydrophobic residues. The computational simulations such as docking and molecular dynamics were finally conducted to detect key residues and folding behaviors in a nano-second range. The kinetic parameters of ESP were measured as K m BANH = 0.97 ± 0.15 mM and k cat / K m BANH = 4.59 s -1 /mM. The time-interval kinetics measurements indicated that ESP inactivation was transformed from a monophase to a biphase process to form a thermodynamically stable state. Spectrofluorimetry measurements showed that serine is directly connected to the regional folding of ESP. Several osmolytes such as proline and glycine only partially protected the inactive form of ESP by serine modification. Computational molecular dynamics and docking simulations showed that three serine residues (Ser183, Ser188, and Ser207) and Cys184, Val206, and Gly209 are key residues of catalytic functions. Our study revealed the functional roles of serine residues as key residues of catalytic function at the active site and of the structural conformation as key folding factors, where ESP displays a flexible property of active site pocket compared to the overall structure.Communicated by Ramaswamy H. Sarma.

A core-shell structure UiO-66-(OH) 2 @UiO-66-NH 2 (MOF@MOF) nanoparticle was synthesized through a simple hydrothermal method and employed as an adsorbent and laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) matrix for the quantitative analysis of rhubarb anthraquinones (RAs). The properties of the materials were characterized by field emission scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, and Brunauer-Emmett-Teller. The results indicate that MOF@MOF is regular octahedral structure with a size distribution of about 100 nm, having large BET specific surface area (920 m 2 /g). Using the MOF@MOF as a matrix shows lower background interference, higher sensitivity, and better storage stability than that of traditional matrices. The MOF@MOF matrix exhibits excellent salt tolerance even under a NaCl concentration of 150 mM. Then, the enrichment conditions were optimized, and the adsorption time of 10 min, adsorption temperature of 40 °C and adsorbent amount of 100 μg were selected. In addition, the possible mechanism of MOF@MOF as an adsorbent and matrix was discussed. Finally, the MOF@MOF nanoparticle was employed as a matrix for the sensitive MALDI-TOF-MS analysis of RAs in spiked rabbit plasma, and the recoveries are in the range of 88.3-101.5% with RSD ≤9.9%. In short, the novel MOF@MOF matrix has demonstrated its potential in the analysis of small-molecule compounds in biological samples., 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., (© 2023 The Authors.)

To deal with problems such as the difficult treatment of low-concentration fluoride-containing water and water pollution caused by excessive fluoride (F - ) discharge, aluminum and zirconium-modified biochar (AZBC) was prepared and its adsorption characteristics and adsorption mechanism for low-concentration fluoride in water were studied. The results showed that AZBC was a mesoporous biochar with uniform pore structure. It could rapidly adsorb F - from water and reach adsorption equilibrium within 20 min. When the initial ρ (F - ) was 10 mg·L -1 and the AZBC dosage was 30 g·L -1 , the removal rate was 90.7%, and the effluent concentration was lower than 1 mg·L -1 . The pH pzc of AZBC was 8.9, and the recommended pH in practical application was 3.2-8.9. The adsorption kinetics accorded with pseudo-second order kinetics, and the adsorption process accorded with the Langmuir model. The maximum adsorption capacities at 25, 35, and 45℃ were 8.91, 11.40, and 13.76 mg·g -1 , respectively. Fluoride could be desorbed by 1 mol·L -1 NaOH. The adsorption capacity of AZBC decreased by approximately 15.9% after 5 cycles. The adsorption mechanisms of AZBC were the combination of electrostatic adsorption and ion exchange.Taking actual sewage as theexperimental object, when the AZBC dosage was 10 g·L -1 , the ρ (F - ) was reduced to below 1 mg·L -1 .

Comprehensive surveillance systems are the key to provide accurate data for effective modeling. Traditional symptom-based case surveillance has been joined with recent genomic, serologic, and environment surveillance to provide more integrated disease surveillance systems. A major gap in comprehensive disease surveillance is to accurately monitor potential population behavioral changes in real-time. Population-wide behaviors such as compliance with various interventions and vaccination acceptance significantly influence and drive the overall epidemic dynamics in the society. Original infoveillance utilizes online query data (e.g., Google and Wikipedia search of a specific content topic such as an epidemic) and later focuses on large volumes of online discourse data about the from social media platforms and further augments epidemic modeling. It mainly uses number of posts to approximate public awareness of the disease, and further compares with observed epidemic dynamics for better projection. The current COVID-19 pandemic shows that there is an urgency to further harness the rich, detailed content and sentiment information, which can provide more accurate and granular information on public awareness and perceptions toward multiple aspects of the disease, especially various interventions. In this perspective paper, we describe a novel conceptual analytical framework of content and sentiment infoveillance (CSI) and integration with epidemic modeling. This CSI framework includes data retrieval and pre-processing; information extraction via natural language processing to identify and quantify detailed time, location, content, and sentiment information; and integrating infoveillance with common epidemic modeling techniques of both mechanistic and data-driven methods. CSI complements and significantly enhances current epidemic models for more informed decision by integrating behavioral aspects from detailed, instantaneous infoveillance from massive social media data., 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., (Copyright © 2023 Chen, Yin, Guo, Ge, Janies, Dulin, Brown, Robinson and Zhang.)

The aim of this study was to characterize the functions of the mitochondrial creatine kinases in the Chinese soft-shelled turtle Pelodiscus sinensis (PSCK-MT1 and PSCK-MT2) to characterize function in relation to hibernation. Computational prediction via molecular dynamics simulations showed that PSCK-MT1 had stronger kinase- and creatine-binding affinity than PSCK-MT2. We measured PSCK-MT1 and PSCK-MT2 levels in the myocardium, liver, spleen, lung, kidney, and ovary of P. sinensis before and after hibernation and found that the expression of these enzymes was the most significantly upregulated in the ovary. We enumerated the ovarian follicles and evaluated the physiological indices of P. sinensis and discovered that fat was the main form of energy storage in P. sinensis . Moreover, both PSCK-MTs promoted follicular development during hibernation. Immunohistochemistry was used to study follicular development and revealed that both PSCK-MTs were expressed primarily in the follicular fluid and granulosa layer before and after hibernation. We found that PSCK-MT1 and PSCK-MT2 could play important roles in ovarian follicular development under hibernation. Hence, both PSCK-MTs probably function effectively under the conditions of low temperature and oxygen during hibernation. Communicated by Ramaswamy H. Sarma.

The soft-shelled turtle, Pelodiscus sinensis, is an important economic aquaculture species. Its reproduction exhibits seasonality; however, there is a lack of systematic studies focused on sperm maturation and epididymal storage. The testes and epididymides of P. sinensis were sampled from March to December. The seasonal reproduction and maturation of the spermatozoa were examined by anatomy, hematoxylin and eosin staining, AB-PAS staining, and immunohistochemistry. Spermatogenesis exhibited obvious seasonality in P. sinensis. It was found that the spermatogenic epithelium was most active during June to September, whereas the diameter of the epididymal tubules was smallest during June to October. As key enzymes of ATP metabolism, creatine kinases were highly expressed in the epididymal tubule epithelium during the breeding season, which may be important for the regulation of sperm maturation. In addition, the epididymal tubule epithelium changed with the season in June to September, the epididymal tubule epithelium proliferated to form villous structures, and secreted a large number of glycoproteins, which may be related to the rapid maturation of sperm during the breeding season. In conclusion, this study provided insights into the spermatogenesis of P. sinensis through histological analysis and enriched our understanding of reproduction in reptiles., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be defined as a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The Chinese soft-shelled turtle, Pelodiscus sinensis (Reptilia: Trionychidae) is a typical seasonal breeding species and its spermatogenesis pattern is complex. In this study, the process of sperm cell development was studied using histology. The process of sperm cell development may be divided into six stages based on a combination of different cell types in the seminiferous epithelium. A close examination revealed two patterns of sperm cell development in the seminiferous tubules during the breeding season. The first is a normal sperm cell development pattern, in which the process of sperm cell development and maturation are completed in the seminiferous epithelium without round spermatozoa in the lumen. The second is rapid sperm cell development, in which the first batches of round spermatozoa fall off the seminiferous epithelium before they mature, thus beginning a second batch of sperm cell development. The round sperm cells are shed into the lumen and further mature in the seminiferous tubules and epididymis. This rapid sperm cell development process of the Chinese soft-shelled turtle is rare in other vertebrate species and may be an adaptation to cope with seasonal breeding. The results of this study provide insight into the theory of seasonal reproduction in reptiles.

Objectives: The current world witnesses a greatly increased prevalence and incidence of hyperuricemia and gout with unfortunately the comparative efficacy and safety of present available uricosuric agents remaining uncertain. We herein aimed to investigate the most appropriate uricosuric agent for gout or hyperuricemia patients., Method: PubMed, Embase, Cochrane Library databases, and ClinicalTrials.gov from inception to 2 July 2022 were searched to retrieve eligible studies assessing efficacy and safety of uricosuric drugs in hyperuricemia or gout patients. Network meta-analysis was carried out using the Stata 16.0 software., Results: Twelve randomized controlled trials comprising 1851 patients were eventually included. Network meta-analysis showed that dotinurad 4 mg once daily, verinurad, dotinurad 2 mg once daily, dotinurad 1 mg once daily, and benzbromarone were the top 5 effective treatments to achieve target serum uric acid. Furthermore, dotinurad 4 mg once daily was more effective at achieving urate-lowering targets (RR of dotinurad 4 mg once daily vs. probenecid: 1.68, 95% CI [1.13; 2.50]) and safer (RR of probenecid vs. dotinurad 4 mg once daily: 1.77, 95% CI [0.69; 4.56]) than probenecid., Conclusions: This network meta-analysis demonstrated an important absolute benefit of dotinurad 4 mg once daily to achieve target serum uric acid and low risk of adverse events for drug treatment of gout or hyperuricemia patients. Additionally, verinurad might be used as an alternative uricosuric therapeutic option to dotinurad. These findings provided further comprehensive insight into the treatment value of current uricosuric agents for gout or hyperuricemia. Key Points 1. This is the first systematic review and network meta-analysis examining the efficacy and safety of currently available uricosuric agents in gout or hyperuricemia patients. 2. Recommended doses of dotinurad 4mg once daily used for the treatment of gout or hyperuricemia patients can significantly decrease serum uric acid levels. 3. The present findings will provide further comprehensive insight into the treatment value of certain uricosuric agents for gout or hyperuricemia., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Histamine H2 receptor antagonists (H2RAs) were widely used to inhibit gastric acid secretion, but its association with adverse events remains controversial and unclear. We conducted an umbrella review of meta-analyses to systematically assess the quality and credibility of the correlations between H2RA use with the risk of adverse outcomes through searching 4 major databases from inception to April 30, 2022. Forty-six individual meta-analyses were identified, including 29 meta-analyses of observation studies with 32 unique outcomes and 19 meta-analyses of randomized controlled trials with 3 unique outcomes for comparing the H2RA versus non-H2RA group. A Measurement Tool to Assess Systematic Reviews 2 rating for the included meta-analyses showed that 4 of 46 meta-analyses were assigned as high scores, 3 were assigned as "moderate," and 25 were assigned as low scores. Grading of Recommendations Assessment, Development and Evaluation assessment for combined results demonstrated that 6 outcomes were rated as "moderate," 9 outcomes were rated as "low," and 17 outcomes were rated as "very low." We confirmed significant associations of H2RA use with pneumonia, peritonitis, necrotizing enterocolitis, Clostridium difficile infection, liver cancer, gastric cancer, and hip fracture diseases. No associations for colorectal cancer, melanoma, kidney cancer, lung cancer, or common reproductive system cancer or renal, neurological, and cardiovascular system diseases were observed. We found a variety of evidence for the associations between H2RAs and adverse outcomes, which would give clinicians more positive guidance on prescription of H2RAs in clinical practice., (© 2022, The American College of Clinical Pharmacology.)

In this study, 3,3',5,5'-tetramethylbenzidine (TMB) was selected as a chromogenic substrate to evaluate the light-responsive oxidase-like activity of different zeolitic imidazolate frameworks (ZIFs). The synthesized ZIFs were systematically characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis. Several main operational parameters, including ZIFs and TMB concentrations, pH value, radiation time, and working current, in the reaction process were optimized. The kinetic measurement results show that ZIF-90 exhibits higher affinity to the substrate than horseradish peroxidase. Furthermore, given that adenosine triphosphate (ATP) can specifically combine with Zn 2+ binding site and destroy the structure of ZIF-90, a specific and sensitive colorimetric method was established for the quantitative detection of ATP within the range 10 - 240 μM. In addition, on the basis that phenolic pollutants can impact the reaction kinetics diversely on different ZIFs, a sensor array was constructed and successfully applied to differentiate five phenolic pollutants in lake water samples. This work is expected to shed light on the establishment of ZIF-based light-responsive oxidase-like nanozymes for the highly selective colorimetric detection and sensor array., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

In this study, the alkaline phosphatase (ALP)-like activity of zeolitic-imidazolate framework-8 (ZIF-8) is reported for the first time. Then, colorimetric sensors for the ascorbic acid oxidase (AAO) and copper ion (Cu 2+ ) detection were developed based on the acetylcholinesterase (AChE)- and ALP-like activities of ZIF-8. The ZIF-8 has good mimetic enzyme activity and exhibits high affinity to the substrates. Its AChE- and ALP-like activities also have good reusability and storage stability. Good linear dependences are obtained in the range of 1.3-250.0 μM (AChE-like activity-based) and 4.5-454.5 μM (ALP-like activity based) for Cu 2+ detection. Furthermore, good linear dependence is also obtained based on the ALP-like activity of ZIF-8 for AAO detection in the range of 2.3-454.5 U/L. Their limits of detection (LODs) are calculated to be 0.7 µM, 2.8 µM, and 1.8 U/L, respectively. Finally, the sample spiked recoveries of Cu 2+ in tap water, Cu 2+ , and AAO in human serum and rabbit plasma were measured, and the results are in the range of 80.0-119.3%. In short, the preparation of ZIF-8 is simple, environmentally friendly, and harmless, and can realize highly selective detection of AAO and Cu 2+ in an efficient and fast process.

In this study, a simple colorimetric method was established to detect copper ion (Cu 2+ ), sulfathiazole (ST), and glucose based on the acetylcholinesterase (AChE)-like activity of zeolitic imidazolate framework-8 (ZIF-8). The AChE-like activity of ZIF-8 can hydrolyze acetylthiocholine chloride (ATCh) to thiocholine (TCh), which will further react with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) to generate 2-nitro-5-thiobenzoic acid (TNB) that has a maximum absorption peak at 405 nm. The effects of different reaction conditions (buffer pH, the volume of ZIF-8, reaction temperature and time, and ATCh concentration) were investigated. Under the optimized conditions, the value of the Michaelis-Menten constant ( K m ) is measured to be 0.83 mM, which shows a high affinity toward the substrate (ATCh). Meanwhile, the ZIF-8 has good storage stability, which can maintain more than 80.0% of its initial activity after 30 days of storage at room temperature, and the relative standard deviation (RSD) of batch-to-batch ( n = 3) is 5.1%. The linear dependences are obtained based on the AChE-like activity of ZIF-8 for the detection of Cu 2+ , ST, and glucose in the ranges of 0.021-1.34 and 5.38-689.66 µM, 43.10-517.24 µM, and 0.0054-1.40 mM, respectively. The limit of detections (LODs) are calculated to be 20.00 nM, 9.25 µM, and 5.24 µM, respectively. Moreover, the sample spiked recoveries of Cu 2+ in lake water, ST in milk, and glucose in strawberry samples were measured, and the results are in the range of 98.4-115.4% with the RSD ( n = 3) lower than 3.3%. In addition, the method shows high selectivity in the real sample analysis.

Arginine kinase is a crucial phosphagen kinase in invertebrates, which is associated to the environmental stress response, plays a key role in cellular energy metabolism. In this study, we investigated the Pb 2+ -induced inhibition and aggregation of Euphausia superba arginine kinase (ESAK) and found that significantly inactivated ESAK in a dose-dependent manner ( IC 50 = 0.058 ± 0.002 mM). Spectrofluorimetry results showed that Pb 2+ induced tertiary structural changes via the internal polarity increased and the non-polarity decreased in ESAK and directly induced ESAK aggregation. The ESAK aggregation process induced by Pb 2+ occurred with multi-phase kinetics. The addition of osmolytes did not show protective effect on Pb 2+ -induced inactivation of ESAK. The computational molecular dynamics (MD) simulation showed that three Pb 2+ interrupt the entrance of the active site of ESAK and it could be the reason on the loss of activity of ESAK. Several important residues of ESAK were detected that were importantly contributed the conformation and catalytic function of ESAK. Our study showed that Pb 2+ -induced misfolding of ESAK and the complete loss of activity irreversibly, which cannot be recovered by osmolytes.Communicated by Ramaswamy H. Sarma.

Objective: To compare and analyze the clinical efficacy of negative pressure wound therapy (NPWT) combined with lavage system in the treatment of Wagner grade 3-5 diabetic foot ulcers combined with infections., Methods: The clinical data of 100 patients with Wagner grade 3-5 diabetic foot ulcers combined with infections admitted to our department between January 2016 and January 2020 were retrospectively analyzed. According to the methods of surgical wound management, they were divided into two groups, a combination treatment group treated by NPWT plus a lavage system and a single treatment group receiving NPWT only. Patients were studied for the types of bacterial infection found in the wounds, the amount of time it took for the wound bacterial culture to turn negative, and the status of blood inflammatory indicators, including white blood cell count and C-reactive protein (CRP). Data concerning hospitalization were collected, including the waiting time before the first operation, the number of operations, length of hospital stay, NPWT usage time, and wound closure time. In addition, data concerning patient condition after discharge were also collected, including the duration of out-of-hospital antibiotic use, the final wound healing rate, the final wound healing time, and long-term wound complications, which include wound dehiscence, new ulcer, infection recurrence, readmission, reoperation, and amputation., Results: There were no statistically significant differences in age, sex, course of disease, lesion side, lesion size and combined diseases between the two groups. Likewise, there was no significant difference in the species and genus, or the composition of bacteria found in the wounds ( P >0.05). However, the combination treatment group showed better results than the single treatment group did in the amount of time it took for wound bacterial culture to turn negative ( P <0.05). As for the blood inflammatory indicators, there was no significant difference between the two groups except that the CRP of the combination group decreased more significantly than that of the single treatment group did at one week postop. The number of surgeries, length of hospital stay, NPWT use time, and wound closure time were lower in the combination treatment group than those in the single treatment group ( P <0.05). However, there was no significant difference in long-term wound complications between the two groups., Conclusion: When applying NPWT plus lavage system in the treatment of Wagner grade 3-5 diabetic foot ulcers combined with infection, wound infection can be controlled effectively at an early stage and the amount of time needed for wound bacterial culture to turn negative can also be reduced. In addition, the combination treatment stimulates granulation growth of the wounds to effectively cover the wound at an early stage., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objectives: Increasing evidence suggested that proton pump inhibitors (PPIs) use might affect the development of cancers, but previous conclusions remain controversial. Therefore, an umbrella review was performed to clarify the associations between PPIs and various types of cancer by summarizing the existing meta-analyses and systematic reviews., Methods: We searched PubMed, Cochrane Library, Embase, CNKI, Wanfang, and VIP database up to June 2022 for eligible meta-analyses or systematic reviews. The summary effect size, 95% CI, heterogeneity, small study effect, and 95% prediction interval were considered in the present study. A Measurement Tool to Assess Systematic Review 2 and grading of recommendation, assessment, development, and evaluation were used to assess methodological quality and evidence., Results: The umbrella review included 21 meta-analyses containing 65 studies and 10 cancer types with 6.8 million subjects. The results showed that PPI use was significantly associated with increased risks of certain types of cancer, including gastric cancer (odds ratio [OR]: 2.07; 95% CI, 1.30 to 3.29), pancreatic cancer (OR: 1.73; 95% CI, 1.23 to 2.44), colorectal cancer (OR: 1.84; 95% CI, 1.26 to 2.67), and liver cancer (OR: 1.80; 95% CI, 1.27 to 2.54), but was not associated with esophageal cancer. In addition, PPI use was associated with decreased risk of breast cancer (OR: 0.69; 95% CI, 0.50 to 0.96)., Conclusions: These findings suggested that clinicians should pay more attention to the occurrence of gastric cancer, pancreatic cancer, colorectal cancer, and liver cancer in patients who used PPIs, and PPI prescription should be written only when an accurate specific diagnosis has been made. Furthermore, additional PPIs to the treatment regimen may be benefit for women with a higher-than-average risk of breast cancer., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Previous studies reported that histamine H2 receptor antagonists (H2RAs) had cardioprotective effects. However, the effect of H2RAs on mortality of critical ill patients with heart failure (HF) remains unclear. The aim of this study was to clarify the association between H2RAs and all-cause mortality of critical ill patients with HF based on Medical Information Mart for Intensive Care III database (MIMIC-III)., Methods and Results: Propensity score matching (PSM) was applied to account for the baseline differences between two groups that were exposed to H2RAs or not. The study primary outcome was all-cause mortality. Kaplan-Meier curves and multivariable Cox regression models were employed to estimate the effects of H2RAs on mortality of critical ill patients with HF. A total of 10 387 patients were included, involving 4440 H2RAs users and 5947 non-H2RAs users. After matching, 3130 pairs of patients were matched between H2RAs users and non-H2RAs users. The results showed significant association between H2RAs exposure and decreased 30-day, 90-day, and 1-year mortality in both univariate analyses and multivariate analyses [hazard ratio (HR) = 0.73, 95% confidence interval (CI): 0.65-0.83 for 30-day; HR = 0.80, 95%CI: 0.72-0.89 for 90-day; and HR = 0.83, 95%CI: 0.76-0.90 for 1-year mortality, respectively] by Cox regression after PSM. Furthermore, stratified analyses revealed that the 30-day, 90-day, and 1-year mortality of ranitidine users were significantly lower than those of famotidine users, respectively., Conclusion: Histamine H2 receptor antagonists exposure was associated with lower mortality in critical ill patients with HF. Furthermore, ranitidine might be superior to famotidine in reducing mortality of critical ill patients with HF., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A simple and time-saving colorimetric method was developed to quantify sulfonamides (SAAs) in milk via inhibition of the human carbonic anhydrase II (hCAII)-like activity of ZIF-8 that can hydrolyze p-nitrophenyl acetate (pNPA) to p-nitrophenol (pNP), following the color change from yellow to colorless. Effects of different reaction conditions, including pH, temperature, amount of ZIF-8, and incubation time, were investigated. The value of Michaelis-Menten constant (K m ) is measured to be 0.15 mM, which exhibits high affinity to pNPA. The IC 50 (0.17, 0.24, and 0.60 mM) and inhibition constant (K i ) (0.09, 0.13, and 0.33 mM) of sulfamethazine (SD), sulfadimethoxine (SDM), and sulfathiazole (ST) on ZIF-8 were measured, respectively. Moreover, the activity of ZIF-8 remains more than 90.0% of its initial activity after 30 days' storage. The colorimetric method for SD, SDM, and ST determination was established at the linear ranges of 6.3-750.0 μM (1.75-208.75 mg/kg), 6.3-750.0 μM (1.96-232.75 mg/kg), and 5.0-1250.0 μM (1.28-319.15 mg/kg) with limit of detection of 4.3, 3.2, and 3.9 μΜ (1.2, 0.99, and 0.96 mg/kg), respectively. In addition, the spiked recoveries of SAAs in milk sample are in the range of 81.6%-106.7% with RSD less than 6.5%. In short, the developed colorimetric method can achieve rapid analysis of SAAs in milk with simple operations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Pyroptosis is a novel inflammatory form of programmed cell death and a prospective target for cancer therapy. Nevertheless, little is known about the association between pyroptosis-related genes (PRGs) and acute myeloid leukemia (AML) prognosis. Herein, we systematically investigated the specific functions and clinical prognostic value of multiple PRGs in AML. Methods: Univariate and LASSO Cox regression analyses based on TCGA and GTEx databases were used to generate the PRG signature, whose predictive efficacy of survival was evaluated using survival analysis, ROC, univariate and multivariate Cox analyses as well as subgroup analysis. The BeatAML cohort was used for data validation. The association between risk score and immune cell infiltration, HLA, immune checkpoints, cancer stem cell (CSC), tumor mutation burden (TMB), and therapeutic drug sensitivity were also analyzed. Results: Six -PRG signatures, namely, CASP3 , ELANE , GSDMA , NOD1 , PYCARD , and VDR were generated. The high-risk score represented a poorer prognosis and the PRG risk score was also validated as an independent predictor of prognosis. A nomogram including the cytogenetic risk, age, and risk score was constructed for accurate prediction of 1-, 3-, and 5-year survival probabilities. Meanwhile, this risk score was significantly associated with the tumor immune microenvironment (TIME). A high-risk score is characterized by high immune cell infiltration, HLA, and immune checkpoints, as well as low CSC and TMB. In addition, patients with low-risk scores presented significantly lower IC50 values for ATRA, cytarabine, midostaurin, doxorubicin, and etoposide. Conclusion: Our findings might contribute to further understanding of PRGs in the prognosis and development of AML and provide novel and reliable biomarkers for its precise prevention and treatment., 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., (Copyright © 2022 Zhou, Qian, Li, Cai, Yin, Wang and He.)

An innovative sandwich-structural Fe-based metal-organic framework magnetic material (Fe 3 O 4 @SW-MIL-101-NH 2 ) was fabricated using a facile solvothermal method. The characteristic properties of the material were investigated by field emission scanning electron microscopy, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction, vibrating sample magnetometry, and Brunauer-Emmett-Teller measurements. Fe 3 O 4 @SW-MIL-101-NH 2 is associated with advantages, such as robust magnetic properties, high specific surface area, and satisfactory storage stability, as well as good selective recognition ability for chlorogenic acid (CA) and its metabolites via chelation, hydrogen bonding, and π-interaction. The results of the static adsorption experiment indicated that Fe 3 O 4 @SW-MIL-101-NH 2 possessed a high adsorption capacity toward CA and its isomers, cryptochlorogenic acid (CCA) and neochlorogenic acid (NCA), and the adsorption behaviors were fitted using the Langmuir adsorption isotherm model. Then, a strategy using magnetic solid-phase extraction (MSPE) and ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF MS/MS) was developed and successfully employed for the selective pre-concentration and rapid identification of CA metabolites in rat plasma, urine, and feces samples. This work presents a prospective strategy for the synthesis of magnetic adsorbents and the high-efficiency pretreatment of CA metabolites., (© 2022 The Authors.)

In this work, a magnetic octahedral metal-organic framework (Fe 3 O 4 @NH 2 -MIL-101(Fe)) was synthesized for the magnetic solid-phase extraction of three anthraquinones, including aloe-emodin, emodin, and physcion, in rhubarb. The Fe 3 O 4 @NH 2 -MIL-101(Fe) exhibits a high specific surface area of 259.2 m 2 /g with an average pore size of 6.0 nm and high magnetic responsivity of 23.4 emu/g, which may be used as an adsorbent for rapid preconcentration and separation of target analytes. The main parameters for magnetic solid-phase extraction of anthraquinones, including the amount of adsorbent, extraction time, extraction temperature, extraction pH, elution solvent, and elution time, were systematically optimized. The whole extraction process requires a very low amount of adsorbent and a small volume of the sample. Besides, under the optimized conditions, the method shows satisfactory spiked recovery for anthraquinones in the range of 93.3-109.1% and the limits of detection are 1.7-3.4 ng/mL. The relative standard deviations for intra- and inter-day precision are 0.2-1.3% and 0.2-0.6%, respectively. The experimental results indicate that the developed method is feasible for the analysis of anthraquinones in rhubarb., (© 2022 Wiley-VCH GmbH.)

Objective: FOXP3 single nucleotide polymorphisms (SNPs) were recently elucidated to influence the development of preeclampsia (PE), but the results on this issue still remained controversial. Thus, a meta-analysis was implemented to systematically investigate the roles of FOXP3 SNPs in PE., Methods: Eligible publications were identified by retrieving relevant electronic databases. Meanwhile, the association intensity was estimated by calculating odds ratios (ORs) and 95% confidence intervals (CIs) in various genetic models., Results: Totally eight investigations involving 3446 subjects were enrolled in the final meta-analysis. The AC and AC + CC genotypes of FOXP3 rs3761548 were related to the susceptibility of PE in over-dominant (OR = 1.19, 95%CI = 1.02-1.38, P = 0.03) and recessive (OR = 0.59, 95% CI: 0.36-0.97, P = 0.04) models. Furthermore, correlation between rs2232365 and PE was observed in recessive model (GG vs. GA + AA) (OR = 0.79, 95%CI: 0.65-0.97, P = 0.03). Moreover, rs2232365 GA and GG + GA genotypes were associated with the severity of PE. However, rs4824747, rs3761547 and rs2280883 polymorphisms had no significant impact on PE susceptibility., Conclusions: FOXP3 rs3761548 and rs2232365 SNPs influenced the PE susceptibility and therefore may be potential biomarkers for prediction of PE risk., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A novel MOF@HOF composite that can serve as a matrix for analysis of small molecules by MALDI-TOF-MS was fabricated through a simple solvothermal method. Taking falvonoids as an example, this composite/matrix presents high desorption/ionization efficiency, low background interference, high salt tolerance, and satisfactory signal reproducibility for MALDI-TOF-MS analysis.

In this study, a highly sensitive visual colorimetric sensor was designed for the detection of trichlorfon based on inhibiting ascorbate oxidase (AAO)-induced metallization of gold nanorods (Au NRs). Ascorbic acid (AA) can reduce silver ion (Ag + ) to metal silver (Ag) that will be deposited on the surface of Au NRs, which results in the blue shift of longitudinal localized surface plasmon resonance (LSPR) peak of Au NRs, accompanying by perceptible color changes from red to cyan to red to yellow. In the presence of trichlorfon, the activity of AAO will be inhibited, resulting in less AA is hydrolyzed to dehydroascorbic acid (DHA), and therefore more Ag + is reduced to Ag by AA. Under the optimized conditions, detection of trichlorfon has a wide linear range of 27.8-11111.1 μg/L with a limit of detection as low as 132.6 ng/L. Moreover, the sensor has a good sample spiked recovery (84.7-96.8%) for the determination of trichlorfon in lake water samples. The proposed method can achieve rapid analysis (about 10 min) of trichlorfon with simple operation when there are no other types of organophosphorus pesticides in the real samples., 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 © 2022 Elsevier B.V. All rights reserved.)

Objective: To assess the efficacy and safety of hypotensive anesthesia (HA) combined with tranexamic acid (TXA) for reducing perioperative blood loss in simultaneous bilateral total hip arthroplasty (SBTHA)., Methods: In this retrospective cohort study, a total of 183 eligible patients (15 females and 168 males, 44.01 ± 9.29 years old) who underwent SBTHA from January 2015 to September 2020 at our medical center were enrolled for analysis. Fifty-nine patients received standard general anesthesia (Std-GA group), the other 85 and 39 patients received HA with an intraoperative mean arterial pressure between 70 and 80 mmHg (70-80 HA group) and below 70 mmHg (<70 HA group), respectively. TXA was administrated to all patients. Perioperative blood loss (total, dominant, and hidden), transfusion rate and volume, hemoglobin and hematocrit reduction, duration of operation and anesthesia, length of hospitalization, range of hip motion as well as postoperative complications were collected from hospital's electronic records and compared between groups., Results: All patients were followed for more than 3 months. Total blood loss in the two HA groups (1390.25 ± 595.67 ml and 1377.74 ± 423.46 ml, respectively) was significantly reduced compared with that in Std-GA group (1850.83 ± 800.73 ml, P < 0.001). Both dominant and hidden blood loss were dramatically decreased when HA was applied (both P < 0.001). Accordingly, the transfusion rate along with volume in 70-80 HA group (14.1%, 425.00 ± 128.81 ml) and <70 HA group (12.8%, 340.00 ± 134.16 ml) were reduced in comparison with those in Std-GA group (37.3%, 690.91 ± 370.21ml; P = 0.001 and P = 0.014, respectively). The maximal hemoglobin and hematocrit reduction in both HA groups were significantly less than those in Std-GA group (both P < 0.001). Of note, 70-80 and <70 HA groups exhibited comparable efficacy with no significant differences between them. Besides, significant difference in duration of surgery was found among groups (P = 0.044 and P < 0.001), while no differences in anesthesia time and postoperative range of hip motion were observed. Regarding complications, the incidence of both acute kidney injury and postoperative hypotension in <70 HA group was significantly higher than that in 70-80 HA and Std-GA groups (P = 0.014 and P < 0.001). Incidence of acute myocardial injury was similar among groups (P = 0.099) and no other severe complications or mortality were recorded., Conclusion: The combination of HA with a mean arterial pressure (MAP) of 70-80 mmHg and TXA could significantly reduce blood loss and transfusion during SBTHA, in addition to shortening operation time and length of hospitalization, and with no increase in complications., (© 2022 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Two liposomes, including 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) + 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (PE) + cholesterol (Chol) (DSPC/PE/Chol liposomes) and soybean lecithin (SPC) + PE + Chol (SPC/PE/Chol liposomes), were prepared and fixed on the inner wall of capillary column by using the adhesion of polydopamine (PDA) membrane and the cross-linking property of glutaraldehyde (GA). The immobilized liposome capillary column (ILCC) has good repeatability and stability based on the electrophoretic mobility of analyte. A CE method based on the immobilized liposome capillary column chromatography (ILCCC) was successfully developed to study the retention behavior of drugs on ILCC, and the logarithm of retention factor (log k) of neutral and ionic drugs were determined. The results show that the log k measured by the ILCCC based on two liposomes have a good linear fitting (R 2 = 0.86). Moreover, the linear relationship between ILCCC system and other related research systems (octanol-water system and immobilized artificial membrane (IAM)) was analyzed, and the results indicate that SPC/PE/Chol ILCCC, DSPC/PE/Chol ILCCC and IAM systems have good fitting results, R 2 values are 0.86 and 0.78, respectively. In addition, the normalization coefficients of ILCCC and IAM systems obtained by the linear free energy relationship (LFER) analysis are close and the d value is small. In short, the ILCCC is a simple and feasible method for studying drug membrane permeability., 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 © 2021 Elsevier B.V. All rights reserved.)

During hibernation of Pelodiscus sinensis , sperm mature and are stored in the epididymis. We investigated seasonal changes in the morphology of epithelial cells of the epididymis of P. sinensis and changes in expression of cytoplasmic creatine kinase (CK). We found that the epididymal epithelium proliferates rapidly to form multiple layers from June to September, while the epididymal epithelial cells are arranged in a single layer from October to May. From the March before the mating period to the end of the mating period in September, a large amount of neutral glycoprotein is secreted in the epididymal epithelium and in the sperm aggregation area; after October, the glycoprotein in the epididymis decreases. At sperm maturation, cytoplasmic CK is expressed abundantly in the villous epithelium, which is formed by proliferation of epididymal epithelial cells. During hibernation and reproduction, the epididymal epithelium of P. sinensis exhibits different proliferation and secretion patterns as the animal adapts to two types of sperm storage. Cytoplasmic CK may participate in regulating the energy metabolism of the epididymal epithelium; it is an important enzyme for regulating sperm maturation.

Objective: Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematological diseases. Previous investigations reported that tumor necrosis factor-alpha (TNF-α) gene polymorphisms were associated with MDS susceptibility, but the results remained controversial. Thus, we conducted a meta-analysis to higher elucidate the correlation between TNF-α gene polymorphisms and MDS susceptibility., Methods: The PubMed, Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched for eligible literatures published up to July 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the strength of association., Results: Eight studies involving 1180 MDS patients and 1387 controls were included in this meta-analysis. For the TNF-α G308A polymorphism, we confirmed that the G allele (G versus A: P  = 0.001), GG genotypes (GG versus GA: P  = 0.005; GG versus GA + AA: P  = 0.002), and GG + AA genotypes (GG + AA versus GA: P  = 0.008) was significantly associated with decreased MDS susceptibility according to different genetic models. Furthermore, the G308A polymorphism was significantly correlated with decreased occurrence risk of MDS in the Caucasian population as compared with Asians in the above four genetic models ( P  < 0.05). However, no significant association was observed between the TNF-α G238A polymorphism and MDS risk., Conclusion: This research showed that TNF-α G308A polymorphism might be a potential biomarker in early clinical screening of MDS, which would contribute to improving the individualized prevention of MDS patients in clinic.

In this study; a spectrum-effect relationship analysis combined with a high-performance liquid chromatography-mass spectrometry (LC-MS) analysis was established to screen and identify active components that can inhibit thrombin and factor Xa (THR and FXa) in Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma (Danshen-Chuanxiong) herbal pair. Ten potential active compounds were predicted through a canonical correlation analysis (CCA), and eight of them were tentatively identified through an LC-MS analysis. Furthermore; the enzyme inhibitory activity of six available compounds; chlorogenic acid; Z -ligustilide; caffeic acid; ferulic acid; tanshinone I and tanshinone IIA; were tested to verify the feasibility of the method. Among them; chlorogenic acid was validated to possess a good THR inhibitory activity with IC 50 of 185.08 µM. Tanshinone I and tanshinone IIA are potential FXa inhibitors with IC 50 of 112.59 µM and 138.19 µM; respectively. Meanwhile; molecular docking results show that tanshinone I and tanshinone IIA; which both have binding energies of less than -7.0 kcal·mol -1 ; can interact with FXa by forming H-bonds with residues of SER214; GLY219 and GLN192. In short; the THR and FXa inhibitors in the Danshen-Chuanxiong herbal pair have been successfully characterized through a spectrum-effect relationship analysis and an LC-MS analysis.

Yolk-shell structure magnetic metal-organic framework nanoparticles were prepared via post solvothermal method and employed as a magnetic solid-phase extraction adsorbent for selective pre-concentration of 5'-ribonucleotides by π stacking interaction, hydrogen bonding, and the strong interaction between titanium ions (Ti 4+ ) and phosphate group. The properties of the materials were confirmed by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectrometry, vibrating sample magnetometer, infrared spectroscopy, thermogravimetric analysis, and Brunauer-Emmett-Teller analysis. The main parameters affecting the adsorption-desorption process, including adsorbent amount, incubation time, incubation temperature, sample pH, shaking speed, elution solution, and elution time, were systematically optimized. Finally, 1.0 mg of adsorbent mixed with 1.0 mL sample solution (10.0 mmol⋅L -1 NaCl, pH 3.0) and shaken at 135 rpm for 5 min at 40 °C, washed with 1.0 mL Na 3 PO 4 -NH 3 ∙H 2 O under vortex for 5 min were selected as optimized adsorption-desorption conditions. The binding performance of adsorbent towards five nucleotides was evaluated by static adsorption experiments. The data are well-fitted to the Langmuir isotherm model and the maximum adsorption capacity is 27.8 mg g -1 for adenosine 5'-monophosphate. The limit of detection of the method is 19.44-38.41 ng mL -1 . Under the optimal conditions, the adsorbent was successfully applied to magnetic solid-phase extraction and high performance liquid chromatography determination of five nucleotides in octopus, chicken, fish, and pork samples., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Aim: A comprehensive meta-analysis was carried out to evaluate the association between high PARP1 expression and clinical outcomes in diverse types of cancers. Materials & methods: The electronic databases for all articles about PARP1 expression and cancers were searched. Additionally, bioinformatics analysis was utilized to validate the results of the meta-analysis. Results: Fifty-two studies with a total of 7140 patients were included in the current meta-analysis. High PARP1 expression was found to be significantly associated with poor overall survival and recurrence in various cancers, which were further strengthened and complemented by the results of bioinformatic analysis. Furthermore, increased PAPR1 expression was also related to clinicopathological features. Conclusion: Our findings confirmed that PARP1 might be a promising biomarker for prognosis in human cancers.

In this study, a magnetic yolk-shell structured metal-organic framework material (Fe 3 O 4 @YS-UiO-66-NH 2 ) is prepared by the directional etching of Co 2+ /peroxymonosulfate and in situ magnetization. The characteristic properties of the material were investigated by using field emission scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometer, Brunauer-Emmett-Teller, and contact angle test. The Fe 3 O 4 @YS-UiO-66-NH 2 shows the advantages of large surface area, good magnetic property, and satisfactory stability, as well as giving high affinity to alkaloids (ALs) via hydrophilic interaction, hydrogen bonding, and π-π interaction. The results of static adsorption experiment indicate that the Fe 3 O 4 @YS-UiO-66-NH 2 possesses high adsorption capacity towards ALs and the adsorption behaviors are fitted with Langmuir adsorption isotherm model. Furthermore, a magnetic solid-phase extraction using Fe 3 O 4 @YS-UiO-66-NH 2 and HPLC method was developed for the analysis of ALs in spiked samples with the recovery of 89.6-100.8%. In addition, the proposed method was successfully applied in the pharmacokinetics study of berberine, coptisine, and palmatine in the rat. In short, the developed method might be used for high-efficient recognition and determination of ALs in plasma sample, which would also provide a new way to fabricate magnetic functionalized metal-organic framework in separation science., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)