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Ping Xu,1 Yi Yun Hu,1 Hai Yan Yuan,1 Da Xiong Xiang,1 Yan Gang Zhou,1 Andrew J Cave,2 Hoan Linh Banh2 1Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410008, People’s Republic of China; 2Department of Family Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, CanadaCorrespondence: Ping XuDepartment of Pharmacy, The Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, Hunan 410008, People’s Republic of ChinaTel +86-138-7488-2504Email xuping1109@163.comHoan Linh BanhDepartment of Family Medicine, Faculty of Medicine and Dentistry, University of Alberta, 6-10 University Terrace, Edmonton, AB, CanadaTel +1 780-248-1835Email hoan@ualberta.caBackground: Prior to 2015, clinical consultation was the only clinical service provided by clinical pharmacists in Changsha Second Hospital. Between 2015 and 2017, a train-the-trainer program was implemented to train clinical pharmacists to provide pharmaceutical care and to conduct clinical research. The objective of the study is to examine the impact on the clinical services provided by pharmacists after the implementation of the train-the-trainer program.Patients and methods: Between 2004 and 2014, all completed clinical consultation activities were tallied and summarized. The results from the tallied consultation activities were used as a baseline for clinical activities provided by pharmacists prior to the training. A structured training program was implemented between 2015 and 2017 to train clinical pharmacists to provide pharmaceutical care. After the implementation of the training program was completed, all clinical activities provided by pharmacists between January 2017 and December 2017 were documented in the clinical workload form. The clinical activities completed by each pharmacist were tallied and summarized.Results: Between 2004 and 2014, a total of 6569 (average 657 per year) pharmacy consultations were requested and completed from a total of 44 departments. In 2017, a total of 15,078 hrs of clinical activities were logged. The pharmacists completed 3481 consultations in 2017 (an increase of 430%), averaging 316 consultations for each pharmacist and 271.8 hr per pharmacist. Over 2000 hrs (of the 15,078 hrs) were spent on direct patient care by the pharmacists.Conclusion: This study shows that there was a 430% increase in clinical pharmacy consultation services provided by the clinical pharmacists after the implementation of the training program. This is directly related to the number of well-trained pharmacists available. After the implementation of the train-the-trainer program, the range of services as well as the number of clinical services and clinical hours spent on providing pharmaceutical care have significantly increased.Keywords: clinical pharmacy, pharmacy consultation, pharmacy services, pharmaceutical care

Despite improvements in surgical techniques and implant design in orthopedic surgery, implantation-associated infections are still a challenging problem for surgeons. In 2006, trace quantities of human β-defensin 3 (hBD-3) were found in human bone tissue and bone cells. Human β-defensin 3 is a 45-amino-acid peptide that is considered the most promising class of defensin antimicrobial peptides and may help in the prevention and treatment of implantation-associated infections. Studies of the effectiveness of hBD-3 against Staphylococcus aureus showed that hBD-3 was more potent at low concentrations than other antibiotics. The effect of hBD-3 on S aureus biofilms has not been reported. We studied the effect of hBD-3, vancomycin, and clindamycin on S aureus biofilms and on the survival of the bacteria in the biofilms.Staphylococcus aureus biofilms were examined with confocal scanning laser microscopy. Staining with LIVE/DEAD BacLight viability stain (Molecular Probes Europe BV, Leiden, The Netherlands) differentiated between live and dead bacteria within the biofilms, and extracellular polymeric substances (slime) from the biofilms was evaluated after staining with calcofluor white (Sigma Chemical Company, Rocky Hill, New Jersey). Human β-defensin 3 and clindamycin reduced the S aureus biofilm area. Human β-defensin 3 was significantly more effective against bacteria from the S aureus biofilms than was clindamycin. Vancomycin did not reduce the S aureus biofilm area. [ABSTRACT FROM AUTHOR]

'Haloarcula aidinensis' was described by a pioneer Chinese scientist focused on halophilic archaea thirty years ago, and the type strain of 'Haloarcula aidinensis' was recently classified based on phylogenetic, phylogenomic, and comparative genomic analyses. Other three novel halophilic archaeal strains, CK38 T , DT43 T , and SYNS111 T , isolated from diverse saline environments in China, were simultaneously subjected to polyphasic classification. 'Haloarcula aidinensis' A 5 was found to be related to Haloarcula amylolytica, while strains CK38 T , DT43 T , and SYNS111 T represented three novel species of Haloarcula based on phylogenetic, phylogenomic, and comparative genomic analyses. These strains can be distinguished from other species within the genus Haloarcula based on multiple phenotypic characteristics. The major phospholipids, phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, and phosphatidylglycerol sulfate can be detected in these strains, while the glycolipid profiles of these strains are diverse. Strains A 5 and DT43 T contained glucosyl mannosyl glucosyl diether and a diglycosyl diether, while other strains CK38 T and SYNS111 T had sulfated mannosyl glucosyl diether and mannosyl glucosyl diether. Thus, strain A 5 should be a reference strain of Har. amylolytica and three novel species of Haloarcula, Haloarcula sediminis sp. nov., Haloarcula brevis sp. nov., and Haloarcula regularis sp. nov. are proposed to accommodate strains CK38 T (= CGMCC 1.62732 T  = JCM 36675 T ), DT43 T (= CGMCC 1.18924 T  = JCM 36146 T ), and SYNS111 T (= CGMCC 1.62601 T  = JCM 36149 T )., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To analyze the dynamic development of physical, psychological, and cognitive degenerative multimorbidity among middle-aged and older Chinese adults (≥45 years old) while estimating the longitudinal association between socioeconomic status (SES) and the progression of multimorbidity. Methods: Based on data from the China Health and Retirement Longitudinal Study (2011-2020), the Sankey diagram was used to show the dynamic development of physical, psychological, and cognitive degenerative multimorbidity from 2011 to 2020. SES was constructed based on the level of education and total household wealth. Logistic regression was used to estimate OR and 95% CI to evaluate the association between SES and the progression of multimorbidity. Results: Of the 5 393 participants included, 4 484 (83.14%) of them developed new diseases, and the prevalence of physical, psychological, and cognitive degenerative multimorbidity increased from 38.04% to 74.23%. Compared to those with no reported disorders at baseline, participants with psychological disorder (for newly developed physical-cognitive multimorbidity: OR =4.59,95% CI : 2.89-7.29), cognitive disorder (for newly developed physical-psychological multimorbidity: OR =2.24,95% CI : 1.40-3.60), or their multimorbidity at baseline were more likely to progress to physical, psychological, and cognitive degenerative multimorbidity. After adjusting covariates, individuals with low SES were more likely to develop physical diseases ( OR= 1.45, 95% CI : 1.11-1.89), cognitive disorder ( OR= 1.84, 95% CI : 1.16-2.91), physical-psychological multimorbidity ( OR= 1.87, 95% CI : 1.37-2.56), physical-cognitive multimorbidity ( OR= 3.58, 95% CI : 2.54-5.06), psychological-cognitive multimorbidity ( OR= 5.66, 95% CI : 3.04-10.55), and physical-psychological-cognitive multimorbidity ( OR= 3.21, 95% CI : 2.06-5.01) in comparison to those with high SES. There is a dose-response relationship between SES and the multimorbidity progression (all trend P <0.001). Conclusions: The prevalence of physical, psychological, and cognitive degenerative multimorbidity increased significantly among middle-aged and older Chinese adults. Lower SES was associated with multiple patterns of physical, psychological, and cognitive disorders progression.

A catalytic formal S N i reaction was designed to achieve stereoretentive products for cis -4-hydroxymethyl-1,2-cyclopentene oxides by using diarylborinic acid as a dual role catalyst and chloride as a catalytic transient nucleophile through a double-displacement mechanism. This reaction offers the advantages of a low catalyst loading of 0.1 mol % and wide substrate scope, even including N -substituents. The use of chiral boron acid as a catalyst for this reaction was also attempted.

One bacterial strain, designated as C22-A2 T , was isolated from Lake LungmuCo in Tibet. Cells of strain C22-A2 T were long rod-shaped, Gram-stain-negative, non-spore-forming, with positive catalase and oxidase activity. Optimal growth occurred at 20-25 °C, pH 8.0 and with 3.0-7.0% (w/v) NaCl. Phylogenetic analysis of 16S rRNA gene and whole genome sequences revealed that strain C22-A2 T belonged to the genus Virgibacillus , showing the highest 16S rRNA gene similarity to Virgibacillus halodenitrificans DSM 10037 T (97.6%). The average nucleotide identity values between strain C22-A2 T and the type strains of related species in the genus Virgibacillus were less than 74.4% and the digital DNA-DNA hybridization values were less than 20.2%, both below the species delineation thresholds of 95 and 70% respectively. The genome analysis revealed that strain C22-A2 T harboured genes responsible for osmotic and oxidative stress, enabling it to adapt to its surrounding environment. In terms of biochemical and physiological characteristics, strain C22-A2 T shared similar characteristics with the genus Virgibacillus, including the predominant cellular fatty acid anteiso-C 15 : 0 , the major respiratory quinone MK-7, as well as the polar lipids phosphatidylglycerol and diphosphatidylglycerol. Based on the comprehensive analysis of phylogenetic, phylogenomic, morphological, physiological and biochemical characteristics, strain C22-A2 T is proposed to represent a novel species of the genus Virgibacillus , named as Virgibacillus tibetensis sp. nov. (=CGMCC 1.19202 T =KCTC 43426 T ).

Motor learning (ML), which plays a fundamental role in growth and physical rehabilitation, involves different stages of learning and memory processes through different brain regions. However, the neural mechanisms that underlie ML are not sufficiently understood. Here, a previously unreported neuronal projection from the dorsal hippocampus (dHPC) to the zona incerta (ZI) involved in the regulation of ML behaviors is identified. Using recombinant adeno-associated virus, the projections to the ZI are surprisingly identified as originating from the dorsal dentate gyrus (DG) and CA1 subregions of the dHPC. Furthermore, projection-specific chemogenetic and optogenetic manipulation reveals that the projections from the dorsal CA1 to the ZI play key roles in the acquisition and consolidation of ML behaviors, whereas the projections from the dorsal DG to the ZI mediate the retrieval/retention of ML behaviors. The results reveal new projections from the dorsal DG and dorsal CA1 to the ZI involved in the regulation of ML and provide insight into the stages over which this regulation occurs., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: To analyze three reconstruction techniques and mid-term clinical outcomes of hip revision for acetabular bone defect after total hip arthroplasty (THA). Methods: This is a retrospective case series study. Included in the study were 109 patients (109 hips) with acetabular bone defect after THA reconstructions in hip revisions from January 2015 to December 2021 in the Senior Department of Orthopaedics, the Forth Medical Center of Chinese People's Liberation Army General Hospital and the Department of Orthopaedics, the First Medical Center of Chinese People's Liberation Army General Hospital. According to the preoperative simulated surgeries and different bone defect reconstruction techniques, patients were divided into a normal cup group, an augment group or a triflange group,respectively. There were 54 patients (54 hips) in the normal cup group, reconstructed with the uncemented porous metal cup (including Jumbo cup), with 23 males and 31 females, aged (59.6±9.9) years (range:32 to 76 years); 44 patients (44 hips) in the augment group, reconstructed with the individualized three-dimensional (3D) printed porous metal augment and uncemented porous metal cup, with 18 males and 26 females, aged (52.8±13.6) years(range:17 to 76 years); 11 patients (11 hips) in the triflange group, reconstructed by the individualized 3D printed porous metal triflange cup, with 5 males and 6 females, aged (59.4±11.2) years (range: 43 to 78 years). Radiographic results, including rotation center height, rotation center offset, and leg length discrepancy (LLD) and clinical results, including Harris hip score (HHS) and visual analogue scale(VAS) were evaluated outpatient at 3, 6, 12 months after the operation and annually thereafter. The last follow-up was completed in March 2024, and all parameters at the last follow-up and before the operation were compared. Paired sample t test and repeated measurement ANOVA were used for the radiographic and clinical parameters before and after the operation. Results: All hip revisions for patients with acetabular bone defect after THA were completed and followed for more than two years. The follow-up time of the normal cup group was (6.5±1.7) years (range: 2.8 to 9.3 years), and that of the augment group was (6.0±1.3) years (range: 3.5 to 9.0 years). The follow-up time of the triflange group was (2.8±0.6) years (range: 2.0 to 3.8 years). At the last follow-up, the rotation center height, rotation center offset and LLD of 54 hips in the normal cup group were (24.2±5.6) mm, (29.1±5.5) mm and (4.6±3.3) mm, respectively, and the rotation center height and LLD were significantly lower than those of the preoperative hips ( t =9.671, P <0.01; t =6.073, P <0.01). In the augment group, the rotational center height, the rotation center offset and the LLD of 44 hips were (22.4±9.0) mm, (25.4±5.5) mm and (6.0±4.0) mm, respectively, which were significantly lower than those of the preoperative hips ( t =9.071, P <0.01; t =11.345, P <0.01; t =4.927, P <0.01). In the triflange group, the rotational center height, the rotation center offset and LLD of 11 hips were (22.7±6.0) mm,(30.9±8.0) mm and (5.3±2.2) mm, respectively, and the rotation center height and LLD were significantly lower than those of the preoperative hips ( t =2.716, P =0.022; t =6.226, P <0.01). At the last follow-up, fractures occurred in 3 patients and dislocation occurred in 1 patient in the normal cup group, and fracture reduction and closed reduction were administered under anesthesia, respectively. In the augment group, dislocation occurred in 1 patient and open reduction under anesthesia was performed. The HHS and VAS of the three groups improved significantly after surgery and the differences were statistically significant (all P <0.01). There was no complication in the triflange group. The X-ray at the last follow-up showed that all prostheses and augments were in stable positions and no loosening or migration was observed. Conclusions: For patients with acetabular bone defect after THA undergoing hip revisions, preoperative surgical simulation and rehearsal could help surgeons choose convenient and efficient reconstruction techniques. The targeted selection of Jumbo cup, individualized 3D printed metal augment, and customized triflange cup could achieve satisfactory clinical outcomes.

Objective: To estimate the longitudinal association between serum lipid biomarkers and the development of cardiometabolic multimorbidity (CMM) in middle-aged and old adults (≥45) in China, while examining effect differences among degree of dyslipidemia aggregation and various dyslipidemia combination patterns. Methods: Based on data from the China Health and Retirement Longitudinal Study (2011-2018), logistic regression analysis was used to evaluate the associations of TC, LDL-C, HDL-C, TG (4 forms of dyslipidemias), degree and pattern of dyslipidemia combination with CMM. We also used restricted cubic splines to show the dose-response associations between 4 lipid biomarkers and CMM development. Results: Of the 6 522 participants included, 590 (9.05%) developed CMM. After adjusting for covariates, all 4 forms of dyslipidemias were positively associated with CMM development (high TC: OR =1.33, 95% CI : 1.03-1.71; high LDL-C: OR =1.35, 95% CI : 1.05-1.75; low HDL-C: OR =1.45, 95% CI : 1.19-1.77; high TG: OR =1.50, 95% CI : 1.20-1.88). The U-shaped dose-response relationship between LDL-C and CMM development was observed ( P for non-linear =0.022). The odds of CMM increased with the increase of dyslipidemias forms, which was highest in those with ≥3 forms of dyslipidemias ( OR =2.02, 95% CI : 1.33-3.06). In various dyslipidemia form combinations, the possibility of CMM development was highest in those with high TC, high LDL-C and low HDL-C ( OR =3.54, 95% CI : 1.40-8.67). High TC and high LDL-C were significantly associated with CMM development in people without cardiometabolic diseases. Low HDL-C was positively associated with diabetes and CMM development in participants without cardiometabolic diseases, cardiovascular disease (CVD) followed by diabetes, and diabetes followed by CVD. High TG was positively associated with diabetes and CMM in participants without cardiometabolic diseases, and diabetes followed by CVD. Conclusions: A total of 4 forms of dyslipidemia were all independently associated with CMM development in middle-aged and old adults in China. The dose-response relationship between LDL-C level and CMM development was U-shaped. The aggregation of 4 forms of dyslipidemia were associated with the development of CMM. Low HDL-C and high TG were significantly associated with multiple patterns of cardiometabolic diseases development.

Advanced oxidation processes (AOPs) are the most efficient water cleaning technologies, but their applications face critical challenges in terms of mass/electron transfer limitations and catalyst loss/deactivation. Bipolar electrochemistry (BPE) is a wireless technique that is promising for energy and environmental applications. However, the synergy between AOPs and BPE has not been explored. In this study, by combining BPE with AOPs, we develop a general approach of using carbon nanotubes (CNTs) as electric-field-induced bipolar electrodes to control electron transfer for efficient water purification. This approach can be used for permanganate and peroxide activation, with superior performances in the degradation of refractory organic pollutants and excellent durability in recycling and scale-up experiments. Theoretical calculations, in situ measurements, and physical experiments showed that an electric field could substantially reduce the energy barrier of electron transfer over CNTs and induce them to produce bipolar electrodes via electrochemical polarization or to form monopolar electrodes through a single particle collision effect with feeding electrodes. This approach can continuously provide activated electrons from one pole of bipolar electrodes and simultaneously achieve "self-cleaning" of catalysts through CNT-mediated direct oxidation from another pole of bipolar electrodes. This study provides a fundamental scientific understanding of BPE, expands its scope in the environmental field, and offers a general methodology for water purification.

Asymmetric hydrogenation of esters through homogeneous catalysis is a significantly important transformation in organic synthesis. The systems developed so far mainly focused on chiral iridium and ruthenium catalysts, which required a base to facilitate the activity. Herein, we present a palladium-catalyzed asymmetric hydrogenation of lactones under base-free conditions through dynamic kinetic resolution and kinetic resolution. The reaction exhibits high enantioselectivity and excellent functional group tolerance. Remarkably, the hydrogenation proceeds smoothly at the gram scale, and the products can be transformed into several chiral potential building blocks without loss of optical purity. This work provides a new strategy for asymmetric hydrogenation of esters under base-free conditions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Adenosine exerts its dual functions of homeostasis and neuromodulation in the brain by acting at mainly 2 G-protein coupled receptors, called A 1 and A 2A receptors. The adenosine A 2A receptor (A 2A R) antagonists have been clinically pursued for the last 2 decades, leading to final approval of the istradefylline, an A 2A R antagonist, for the treatment of OFF-Parkinson's disease (PD) patients. The approval paves the way to develop novel therapeutic methods for A 2A R antagonists to address 2 major unmet medical needs in PD and traumatic brain injury (TBI), namely neuroprotection or improving cognition. In this review, we first consider the evidence for aberrantly increased adenosine signaling in PD and TBI and the sufficiency of the increased A 2A R signaling to trigger neurotoxicity and cognitive impairment. We further discuss the increasing preclinical data on the reversal of cognitive deficits in PD and TBI by A 2A R antagonists through control of degenerative proteins and synaptotoxicity, and on protection against TBI and PD pathologies by A 2A R antagonists through control of neuroinflammation. Moreover, we provide the supporting evidence from multiple human prospective epidemiological studies which revealed an inverse relation between the consumption of caffeine and the risk of developing PD and cognitive decline in aging population and Alzheimer's disease patients. Collectively, the convergence of clinical, epidemiological and experimental evidence supports the validity of A 2A R as a new therapeutic target and facilitates the design of A 2A R antagonists in clinical trials for disease-modifying and cognitive benefit in PD and TBI patients., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Impact electrochemistry allows for the investigation of the properties of single entities, ranging from nanoparticles (NPs) to soft bio-particles. It has introduced a novel dimension in the field of biological analysis, enhancing researchers' ability to comprehend biological heterogeneity and offering a new avenue for developing novel diagnostic devices for quantifying biological analytes. This review aims to summarize the recent advancements in impact electrochemistry-based biosensing over the past two to three years and provide insights into the future directions of this field.

Objective: The study analyzed the impact of urbanization on epidemiological characteristics of respiratory infectious disease in Tongzhou District, Beijing during 2014-2022 to provide reference for prevention and control priorities of respiratory infectious diseases during the innovative urbanization process in China., Methods: The incidence data of notifiable respiratory infectious diseases (NRIDs) in Tongzhou Beijing during 2014-2022 were summarized. The trend of incidence rate was analyzed by Joinpoint regression model, and entropy method was performed to construct the comprehensive index of urbanization (CIU) and generalized linear model was used to analyze the influence of CIU on the incidence rate of respiratory infectious diseases., Results: Totally 72616 NRIDs cases were reported in Tongzhou District during 2014-2022, and the incidence rate of NRIDs was higher during 2017-2019 (153/100 000) than during 2014-2016 (930/100 000) and during 2020-2022 (371/100 000), respectively (both P < 0.001). The CIU constantly increased with slight fluctuation in 2016 and 2018, respectively. The incidence rate of NRIDs showed an increase along with the CIU during 2014-2019 ( r  = 0.95, P = 0.004), while the incidence rate's tendency was interrupted by COVID-19 during 2020 with slight decrease in 2020-2021 and rebounded in 2022. For the patients aged <15 years, the incidence rate of NRIDs revealed a very sharp rise at the urbanization period without COVID-19 pandemic compared with that under pre-urbanization period (RR = 7.93, 95 % CI 7.63-8.24), and dropped off to the similar level as of pre-urbanization period when COVID-19 pandemic spread., Conclusions: Urbanization process may increase the incidence of NRIDs but constrained by COVID-19. Certain measures should be taken to prevent and control the effects by urbanization process, such as good natural environment with less population density, ecological environment with good air quality, promoted hand hygiene, mask wearing, keeping interpersonal distance, vaccination, media publicity for NRIDs' prevention and control., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The chiral 4,5,6,7-tetrahydropyrazolo[1,5- a ]pyrimidine is the key core skeleton of potent Bruton's tyrosine kinase (BTK) inhibitor Zanubrutinib, and the catalyst-controlled asymmetric hydrogenation of planar multinuclear pyrimidine heteroarenes with multiple N atoms could provide an efficient route toward its synthesis. Owing to the strong aromaticity and poisoning effect toward chiral transition metal catalyst, asymmetric hydrogenation of pyrazolo[1,5- a ]pyrimidines with multiple nitrogen atoms is still a challenge for synthesizing the chiral 4,5,6,7-tetrahydropyrazolo[1,5- a ]-pyrimidine. Herein, an efficient iridium-catalyzed asymmetric hydrogenation of pyrazolo[1,5- a ]pyrimidines has been developed using substrate activation strategy, with up to 99% ee. The decagram scale synthesis further demonstrated the potential and promise of this procedure in the synthesis of Zanubrutinib. In addition, a mechanistic study indicated that the hydrogenation starts with 1,2-hydrogenation.

Using readily available manganese pentacarbonyl bromide as a regeneration catalyst, biomimetic asymmetric reduction of imines including quinoxalinones, benzoxazinones, and benzoxazine has been successfully developed in the presence of transfer catalyst chiral phosphoric acids, providing the chiral amines with high yields and enantioselectivities.

Two Gram-positive, rod-shaped, endospore-forming strains, YIM B05601 and YIM B05602 T , were isolated from soil sampled at Hamazui hot spring, Tengchong City, Yunnan Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences suggested that the two strains fell within the genus Paenibacillus , appearing most closely related to Paenibacillus alkalitolerans YIM B00362 T (96.9 % sequence similarity). Genome-based phylogenetic analysis confirmed that strains YIM B05601 and YIM B05602 T formed a distinct phylogenetic cluster within the genus Paenibacillus . The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values of strains YIM B05601 and YIM B05602 T with the related species P. alkalitolerans YIM B00362 T were within the ranges of 74.43-74.57 % and 12.1-18.5 %, respectively, which clearly indicated that strains YIM B05601, YIM B05602 T represented a novel species. Strains YIM B05601 and YIM B05602 T exhibited 99.6 % 16S rRNA gene sequence similarity. The ANI and dDDH values between the two strains were 99.8 and 100 %, respectively, suggesting that they belong to the same species. Optimum growth for both strains occurred at pH 7.0 and 45 °C. The diagnostic diamino acid in the cell-wall peptidoglycan of strains YIM B05601 and YIM B05602 T was meso -diaminopimelic acid. MK-7 was the predominant menaquinone. The polar lipids of strain YIM B05602 T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, four unidentified glycolipids, an unidentified polarlipid and phosphatidylinositol mannoside. The major fatty acids of the two stains were iso-C 15 : 0 and anteiso-C 15 : 0 . Based on phylogenomic and phylogenetic analyses coupled with phenotypic and chemotaxonomic characterizations, strains YIM B05601 and YIM B05602 T could be classified as a novel species of the genus Paenibacillus , for which the name Paenibacillus thermotolerans sp. nov. is proposed. The type strain is YIM B05602 T (=CGMCC 1.60051 T =KCTC 43460 T =NBRC 115924 T ).

Advanced techniques for both environmental and biological prescription drug monitoring are of ongoing interest. In this work, a fluorescent sensor based on an Eu 3+ -doped anionic zinc-based metal-organic framework (Eu 3+ @Zn-MOF) was constructed for rapid visual analysis of the prescription drug molecule demecycline (DEM), achieving both high sensitivity and selectivity. The ligand 2-amino-[1,1'-biphenyl]-4,4'-dicarboxylic acid (bpdc-NH 2 ) not only provides stable cyan fluorescence (467 nm) for the framework through intramolecular charge transfer of bpdc-NH 2 infinitesimal disturbanced by Zn 2+ but also chelates Eu 3+ , resulting in red (617 nm) fluorescence. Through the synergy of photoinduced electron transfer and the antenna effect, a bidirectional response to DEM is achieved, enabling concentration quantification. The Eu 3+ @Zn-MOF platform exhibits a wide linear range (0.25-2.5 μM) to DEM and a detection limit (LOD) of 10.9 nM. Further, we integrated the DEM sensing platform into a paper-based system and utilized a smartphone for the visual detection of DEM in water samples and milk products, demonstrating the potential for large-scale, low-cost utilization of the technology.

Protein kinase activity correlates closely with that of many human diseases. However, the existing methods for quantifying protein kinase activity often suffer from limitations such as low sensitivity, harmful radioactive labels, high cost, and sophisticated detection procedures, underscoring the urgent need for sensitive and rapid detection methods. Herein, we present a simple and sensitive approach for the homogeneous detection of protein kinase activity based on nanoimpact electrochemistry to probe the degree of aggregation of silver nanoparticles (AgNPs) before and after phosphorylation. Phosphorylation, catalyzed by protein kinases, introduces two negative charges into the substrate peptide, leading to alterations in electrostatic interactions between the phosphorylated peptide and the negatively charged AgNPs, which, in turn, affects the aggregation status of AgNPs. Via direct electro-oxidation of AgNPs in nanoimpact electrochemistry experiments, protein kinase activity can be quantified by assessing the impact frequency. The present sensor demonstrates a broad detection range and a low detection limit for protein kinase A (PKA), along with remarkable selectivity. Additionally, it enables monitoring of PKA-catalyzed phosphorylation processes. In contrast to conventional electrochemical sensing methods, this approach avoids the requirement of complex labeling and washing procedures.

Nanomedicine is promising for disease prevention and treatment, but there are still many challenges that hinder its rapid development. A major challenge is to efficiently seek candidates with the desired therapeutic functions from tremendously available materials. Here, we report an integrated computational and experimental framework to seek alloy nanoparticles from the Materials Project library for antibacterial applications, aiming to learn the inverse screening concept from traditional medicine for nanomedicine. Because strong peroxidase-like catalytic activity and weak toxicity to normal cells are the desired material properties for antibacterial usage, computational screening implementing theoretical prediction models of catalytic activity and cytotoxicity is first conducted to select the candidates. Then, experimental screening based on scanning probe block copolymer lithography is used to verify and refine the computational screening results. Finally, the best candidate AuCu 3 is synthesized in solution and its antibacterial performance over other nanoparticles against S. aureus and E. coli . is experimentally confirmed. The results show the power of inverse screening in accelerating the research and development of antibacterial nanomedicine, which may inspire similar strategies for other nanomedicines in the future.

The proton of alcohols as the sole hydrogen source in diboron-mediated nickel-catalyzed asymmetric transfer hydrogenation of cyclic N -sulfonyl imines has been developed, providing the chiral cyclic sulfamidates in excellent enantioselectivities. The mechanistic investigations suggested that the proton of alcohols could be activated by tetrahydroxydiboron to form active nickel hydride species.

An unprecedented dearomatization of [2.2]paracyclophane-derived cyclic N -sulfonylimines was conducted through cyclopropanation with sulfur ylides, giving a series of dearomative cyclopropanes with good yields. DFT calculations suggested that the dearomatization was attributed to the relatively weak aromaticity of [2.2]paracyclophane derivatives that resulted from the effect of the unique [2.2]paracyclophane skeleton and the electron-withdrawing N -sulfonyl group. Some downstream elaborations of the products were demonstrated.

Aims: Adenosine 2A receptor (A 2A R) is widely expressed in the brain and plays important roles in neuroinflammation, and the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a crucial component of the innate immune system while the regulation of A 2A R on it in the central nervous system (CNS) has not been clarified., Methods: The effects of microglial A 2A R on NLRP3 inflammasome assembly and activation were investigated in wild-type, A 2A R- or NLRP3-knockout primary microglia with pharmacological treatment. Microglial A 2A R or NLRP3 conditional knockout mice were used to interrogate the effects of this regulation on neuroinflammation posttraumatic brain injury (TBI)., Results: We found that A 2A R directly interacted with NLRP3 and facilitated NLRP3 inflammasome assembly and activation in primary microglia while having no effects on mRNA levels of inflammasome components. Inhibition of the interaction via A 2A R agonist or knockout attenuated inflammasome assembly and activation in vitro. In the TBI model, microglial A 2A R and NLRP3 were co-expressed at high levels in microglia next to the peri-injured cortex, and abrogating of this interaction by microglial NLRP3 or A 2A R conditional knockout attenuated the neurological deficits and neuropathology post-TBI via reducing the NLRP3 inflammasome activation., Conclusion: Our results demonstrated that inhibition of the interaction between A 2A R and NLRP3 in microglia could mitigate the NLRP3 inflammasome assembly and activation and ameliorate the neuroinflammation post-TBI. It provides new insights into the effects of A 2A R on neuroinflammation regulation post-TBI and offers a potential target for the treatment of NLRP3 inflammasome-related CNS diseases., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Plasmon-enhanced electrochemistry (PEEC) has been observed to facilitate energy conversion systems by converting light energy to chemical energy. However, comprehensively understanding the PEEC mechanism remains challenging due to the predominant use of ensemble-based methodologies on macroscopic electrodes, which fails to measure electron-transfer kinetics due to constraints from mass transport and the averaging effect. In this study, we have employed nanoparticle impact electrochemistry (NIE), a newly developed electroanalytical technique capable of measuring electrochemical dynamics at a single-nanoparticle level under optimal mass transport conditions, along with microscopic electron-transfer theory for data interpretation. By investigating the plasmon enhanced hydrogen evolution reaction (HER) at individual silver nanoparticles (AgNPs), we have clearly revealed the previously unknown influence of solvent effects within the PEEC mechanism. This finding suggests an additional approach to optimize plasmon-assisted electrocatalysis and electrosynthesis systems.

It is challenging to enantioselectively construct molecules bearing multiple nonadjacent stereocenters, in contrast to those bearing a single stereocenter or adjacent stereocenters. Herein, we report an enantio- and diastereoselective synthesis of substituted chiral allenes with nonadjacent axial and two central chiral centers through a combination of retro-oxa-Michael addition and palladium-catalyzed asymmetric allenylic alkylation. This methodology exhibits good functional-group compatibility, and the corresponding allenylic alkylated compounds, including flavonoid frameworks, are obtained with good yields and diastereoselectivities and excellent enantioselectivities (all >95% ee). Furthermore, the scalability of the current synthetic protocol was proven by performing a gram-scale reaction.

A diarylborinic acid-catalyzed ring opening of cis -4-hydroxymethyl-1,2-cyclopentene oxides was developed with N -nucleophiles including anilines, benzotriazole, and alkylamines, as well as S -nucleophiles, affording 1,2,4-trisubstituted cyclopentane compounds containing a quaternary carbon center. The mechanism study indicated that the "half-cage" structure formed by the epoxide substrate and the catalyst prevents the nucleophiles from attacking the inner side of the "half-cage", resulting in the desired ring-opening product.

Prussian blue (PB) has emerged as a promising cathode material in aqueous batteries. It possesses two distinct redox centers, and the potassium ions (K + ) are unevenly distributed throughout the compound, adding complexity to the interpretation of the K + insertion/de-insertion kinetic mechanism. Traditional ensemble-averaged measurements are limited in uncovering the precise kinetic information of the PB particles, as the results are influenced by the construction of the porous composite electrode and the redox behavior from different particles. In this study, the electrochemical processes of individual PB particles were investigated using nano-impact electrochemistry. By varying the potentials, different types of transient current signals were obtained that revealed the kinetic mechanism of each oxidation/reduction reaction in combination with theoretical simulation. Additionally, a partially contradictory conclusion between single-particle analysis and the ensemble-averaged measurement was discussed. These findings contribute to a better understanding of the electrochemical processes of cathode materials with multiple redox centers, which facilitates the development of effective strategies to optimize these materials., (© 2023 Wiley-VCH GmbH.)

Nanoparticle impact electrochemistry (NIE) is an emerging electroanalytical technique that has been utilized to the sensitive detection of a wide range of biological species. So far, the NIE based trace ion detection is largely unexplored due to the lack of effective signal amplification strategies. We herein develop an NIE-based electrochemical sensing platform that utilizes T-Hg 2+ -T coordination induced AgNP aggregation to detect Hg 2+ in aqueous solution. The proposed aggregation-collision strategy enables highly sensitive and selective detection. A dual-mode analysis based on the change in impact frequency and oxidative charge of the anodic oxidation of the AgNPs in NIE allows for more accurate self-validated quantification. Furthermore, the current NIE-based sensor demonstrates reliable analysis of Hg 2+ of real water samples, showing great potential for practical environmental monitoring and point-of-care testing (POCT) applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 Elsevier B.V. All rights reserved.)

The friction stir welding (FSW) of thermoplastic polymers is gradually receiving attention because of its advantages including high efficiency and pollution-free manufacturing. The extrusion-based additive manufacturing (EAM) of polymers has also become one of the main processing methods for thermoplastic parts. In this paper, a hybrid manufacturing method for the FSW process and EAM technology is proposed and explored. The effects of the FSW process using two different welding tools on the mechanical behaviors of 3D printing polymer parts were compared and investigated and the corresponding mechanism was analyzed. The results show that the appropriate welding tool is beneficial for eliminating the anisotropy and decreasing the porosity of 3D-printed parts. Therefore, the improving effects of the FSW process on the mechanical behaviors of the EAM parts are verified. The mechanism was attributed to the high-speed rotation of the welding tool with the appropriate shape, which can promote the flow of polymer melt in the welding region, leading to the formation of dense structures caused by the entanglement of the molecular chains. This study may provide some assistance in modern industrial manufacturing for the processing of large custom components.

ConspectusIn nature, the coenzyme NAD(P)H is utilized for the transfer of hydrogen and electrons in biocatalytic reduction, which involves the process of recycling, coenzyme usage, and reduction. Inspired by the biological system, a series of nonregenerable achiral and chiral NAD(P)H models were synthesized and employed. However, this approach faced intractable limitations, such as the need for an equivalent amount of mimics, accompanied by the production of byproducts, which resulted in poor atom economy and difficult separation of products. Therefore, the development of new and efficient methodologies for synthesis, regeneration, and application of the NAD(P)H models in organic synthesis is greatly desired.To tackle these challenges, the regenerable achiral and chiral coenzyme NAD(P)H models were designed and synthesized based on the principles of biocatalytic reduction and applied them in biomimetic asymmetric reduction (BMAR) reactions. This Account summarizes our endeavors in rational design, synthesis, regeneration, and application of the NAD(P)H models. First, we will introduce the design and synthesis of regenerable and achiral coenzyme NAD(P)H models (dihydrophenanthridine and dihydropyrroloquinoxaline), which were successfully applied to BMAR of imines and heteroaromatics using homogeneous ruthenium complex as a regeneration catalyst, chiral phosphoric acid as a transfer catalyst, and hydrogen as the terminal reductant. Regenerable and achiral NAD(P)H models require the addition of chiral catalysts or chiral ligands for stereoselective control during the BMAR process. However, the screening of the chiral transfer catalysts is tedious. Narrow substrate scope further limited their application in organic synthesis. Therefore, we designed and synthesized regenerable and chiral NAD(P)H models (CYNAM and FENAM) with planar chirality, which were successfully applied in asymmetric reduction of imines and heteroaromatics using commercially available achiral Brønsted acids, Lewis acids, or organocatalysts as transfer catalysts and a homogeneous ruthenium complex as a regeneration catalyst. Notably, the original factor of enantioselective control is from the chiral NAD(P)H models. In addition, this strategy could also realize the asymmetric reduction of a myriad of electron-deficient tetrasubstituted alkenes, which are challenging substrates in transition metal catalyzed asymmetric hydrogenation. This methodology provides an efficient strategy for the synthesis of chiral building blocks and bioactive molecules. Finally, the detailed mechanism of BMAR, based on the regenerable NAD(P)H models, was elaborated through a combination of experiments and density functional theory calculations. In summary, we believe that the results presented in this Account hold significant implications beyond our work and have the potential for further applications in the field of biomimetic asymmetric catalysis and synthetic methodology.

Background: Although ceramic-on-ceramic (CoC) bearings result in the lowest wear rate of any bearing combination, postoperative squeaking remains worrisome. However, data concerning squeaking in long-term follow-up studies are still lacking, especially for fourth-generation CoC THA., Questions/purposes: (1) After keeping the prosthesis in place for 10 years, what percentage of patients treated with fourth-generation CoC THA implants report squeaking, and are there points in time when squeaking occurs more frequently? (2) What are the characteristics, association with hip function, and factors associated with squeaking? (3) Can we create a nomogram that characterizes a patient's odds of experiencing squeaking based on the factors associated with it?, Methods: Between January 2009 and December 2011, 1050 patients received primary THAs at our institution, 97% (1017) of whom received fourth-generation CoC THAs because this was the preferred bearing during this period. Of the 1017 eligible patients, 5% (54) underwent THAs performed by low-volume surgeons, 3% (30) were implanted with cemented prostheses, 2% (22) died, 1% (10) were immobile, 1% (six) underwent revision surgery, and 17% (169) were lost to follow-up before 10 years, leaving 726 patients for analysis here at a mean of 11 ± 1 years. In the study cohort, 64% (464) were male and 36% (262) were female, with a mean age of 44 ± 13 years at primary THA. We extracted data about articular noise from follow-up records in our institutional database and used a newly developed questionnaire to ascertain the percentage of patients who reported squeaking at the latest follow-up interval. Although not validated, the questionnaire was modeled on previous studies on this topic. The longitudinal pattern for squeaking was explored to find timepoints when squeaking occurs more frequently. Based on the questionnaire data, we calculated the percentages of frequent, reproducible, and avoidable squeaking. Hip function was evaluated with the Harris Hip Score and WOMAC score and compared between the squeaking and nonsqueaking groups. Factors associated with squeaking, which were examined in a multivariate analysis, were used to develop a nomogram., Results: At 10 years, 16% (116 of 726) of patients reported squeaking. Two squeaking peaks were determined, at 0 to 1 year and 8 to 10 years. Frequent, reproducible, and avoidable squeaking accounted for 42% (36 of 86), 20% (17 of 86), and 41% (35 of 86), respectively. The mean Harris Hip Score (93 ± 4 versus 94 ± 5; p = 0.81) and WOMAC score (16 ± 13 versus 15 ± 13; p = 0.23) did not differ between patients with squeaking and those without. After controlling for potential confounding variables such as etiology and head offset, we found that patients younger than 46 years (odds ratio 2.5 [95% confidence interval 1.5 to 5.0]; p < 0. 001), those who were male (OR 2.0 [95% CI 1.1 to 3.5]; p = 0.04), those having a total flexion and extension arc of less than 50° (OR 2.0 [95% CI 1.2 to 3.3]; p = 0.02), and those with the Corail hip implant (OR 4.1 [95% CI 2.1 to 7.7]; p < 0. 001) were more likely to report squeaking. We created a nomogram that can be used at the point of care that can help clinicians identify patients at a higher risk of experiencing squeaking; this nomogram had good performance (area under the receiver operating characteristic curve of 77%)., Conclusion: As a potential late complication, squeaking after fourth-generation CoC THA is of concern and may be related to increased stripe wear. We recommend that surgeons use this nomogram to assess the odds of squeaking before selecting a bearing, especially in patients at high risk, to facilitate shared decision-making and improve patient satisfaction. Future external validation of the model is still needed to enhance its applicability.Level of Evidence Level III, therapeutic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

A series of [2,2]paracyclophane-based tridentate PNO ligands with planar chirality were designed and synthesized. The easily prepared chiral tridentate PNO ligands were successfully applied to the iridium-catalyzed asymmetric hydrogenation of simple ketones, giving chiral alcohols with high efficiency and excellent enantioselectivities (up to 99% yield and >99% ee). Control experiments revealed the indispensability of both N-H and O-H in the ligands.

Purpose: Influenza virus (IFV) causes acute respiratory tract infection (ARTI) and leads to high morbidity and mortality annually. This study explored the epidemiological change of IFV after the implementation of the universal two-child policy and evaluated the impact of coronavirus disease 2019 (COVID-19) pandemic on the detection of IFV., Methods: Hospitalized children under 18 years with ARTI were recruited from Hubei Maternal and Child Healthcare Hospital of Hubei Province from January 2014 to June 2022. The positive rates of IFV were compared among different periods by the implementation of the universal two-child policy and public health measures against COVID-19 pandemic., Results: Among 75,128 hospitalized children with ARTI, the positive rate of IFV was 1.98% (1486/75128, 95% CI 1.88-2.01). Children aged 6-17 years had the highest positive rate of IFV (166/5504, 3.02%, 95% CI 2.58-3.50). The positive rate of IFV dropped to the lowest in 2015, then increased constantly and peaked in 2019. After the universal two-child policy implementation, the positive rate of IFV among all the hospitalized children increased from 0.40% during 2014-2015 to 2.70% during 2017-2019 (RR 6.72, 95% CI 4.94-9.13, P < 0.001), particularly children under one year shown a violent increasing trend from 0.20 to 2.01% (RR 10.26, 95% CI 5.47-19.23, P < 0.001). During the initial outbreak of COVID-19, the positive rate of IFV decreased sharply compared to that before COVID-19 (0.35% vs. 3.37%, RR 0.10, 95% CI 0.04-0.28, P < 0.001), and then rebounded to 0.91%, lower than the level before COVID-19 (RR 0.26, 95% CI 0.20-0.36, P < 0.001)., Conclusion: IFV epidemiological pattern has changed after the implementation of the universal two-child policy. More attention should be emphasized to comprehend the health benefits generated by COVID-19 restrictions on IFV transmission in future., (© 2023. The Author(s).)

The formation of fear memory is crucial in emotional disorders such as PTSD and anxiety. Traumatic brain injury (TBI) can cause emotional disorders with dysregulated fear memory formation; however, their cross-interaction remains unclear and hurdled the treatment against TBI-related emotional disorders. While adenosine A2A receptor(A2AR) contributes to the physiological regulation of fear memory, this study aimed to evaluate the A2AR role and possible mechanisms in post-TBI fear memory formation using a craniocerebral trauma model, genetically modified A2AR mutant mice, and pharmacological A2AR agonist CGS21680 and antagonist ZM241385. Our finding showed (i) TBI enhanced mice freezing levels (fear memory) at seven days post-TBI; (ii) The A2AR agonist CGS21680 enhanced the post-TBI freezing levels; conversely, the A2AR antagonist ZM241385 reduced mice freezing level; further (iii) Genetic knockdown of neuronal A2AR in the hippocampal CA1, CA3, and DG regions reduced post-TBI freezing levels, while A2AR knockout in DG region yielded the most reduction in fear memory; finally, (iv) AAV-CaMKII-Cre virus-mediated DG deletion of A2AR on excitatory neurons led to a significant decreased freezing levels post-TBI. These findings indicate that brain trauma increases fear memory retrieval post-TBI, and A2AR on DG excitatory neurons plays a crucial role in this process. Importantly, inhibition of A2AR attenuates fear memory enhancement, which provides a new strategy to prevent fear memory formation/enhancement after TBI., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

In this work, we report a versatile and tunable platform for the construction of various cell array biochips using a simple soft lithographic approach to pattern polydopamine (PDA) arrays via microcontact printing (μCP). Instead of direct polymerization of PDA on the polydimethylsiloxane (PDMS) tips, dopamine monomers were first printed on the substrate followed by a self-oxidative polymerization step facilitated by ammonia vapor to grow PDA in situ, which greatly reduced the reaction time and prevented the PDMS tips from damaging. The improved robustness and utility of the PDMS tips allows the formation of tunable PDA array chips with controllable PDA feature size and shape. As a result, single cell, multi-cells and cell line arrays can be constructed. The obtained cell array chips showed high single cell capture efficiency, providing a standardized single cell array analysis platform. Meanwhile, the adhered cells can maintain excellent viability and proliferation ability on the PDA chips. Moreover, a cytotoxicity sensor with single cell resolution was enabled on the single cell array chip. This work provides a promising cell array biochip platform for high-throughput cellular analysis and cell screening., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We report a Brønsted acid-catalyzed C6 functionalization of 2,3-disubstituted indoles with 2,2-diarylacetonitriles for efficient construction of cyano-substituted all-carbon quaternary centers with excellent yields. The synthetic utility was demonstrated by the conversion of the cyano-group which enables the divergent preparation of aldehydes, primary amines and amides. Control experiments suggested that this process involves C-H oxidation of 2,2-diarylacetonitriles to in situ generate δ , δ -disubstituted p -quinone methide intermediates. This protocol provides an efficient method for C6 functionalization of 2,3-disubstituted indoles to construct all-carbon quaternary centers.

The development of a new strategy for the construction of chiral cyclic sulfide-containing multiple stereogenic centers is highly desirable. Herein, by the combination of base-promoted retro-sulfa-Michael addition and palladium-catalyzed asymmetric allenylic alkylation, the streamlined synthesis of chiral thiochromanones containing two central chiralities (including a quaternary stereogenic center) and an axial chirality (allene unit) was successfully realized with up to 98% yield, 49.0 : 1 dr and >99% ee., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Here we report the first palladium-catalyzed asymmetric hydrogenolysis of readily available aryl triflates via desymmetrization and kinetic resolution for facile construction of axially chiral biaryl scaffolds with excellent enantioselectivities and s selectivity factors. The axially chiral monophosphine ligands could be prepared from these chiral biaryl compounds and were further applied to palladium-catalyzed asymmetric allylic alkylation with excellent ee values and high branched and linear ratio, which demonstrated the potential utility of this methodology., (© 2023 Wiley-VCH GmbH.)

Zinc(II)-catalyzed [2+2+1] annulation of internal alkenes, diazooxindoles, and isocyanates was successfully developed for the construction of multisubstituted spirooxindoles. This multicomponent transformation involves in situ generation of a sulfur-containing spirocyclic intermediate from the [4+1] annulation of diazooxindole to sulfonyl isocyanate, which subsequently reacts as a 1,3-dipole with the internal alkene, that is, α-oxo ketene dithioacetal, to furnish a formal [2+2+1] annulation in a one-pot manner. This synthetic protocol features a low-toxicity main group metal catalyst, readily available reagents, and ≤96% yields, offering an efficient route to multisubstituted spirooxindole derivatives.

Five aerobic, Gram-stain-negative, non-motile, non-spore-forming, short rod bacteria strains, designated as C3-1-R+6 T , C3-2-M9, B3-2-R-7, B3-2-R-21 and C3-2-M2, were isolated from shore soil of LungmuCo Lake in Tibet of China. The 16S rRNA gene sequence comparisons confirmed their affiliation to the genus Parapedobacter of the family Sphingobacteriaceae , and showed that they were most closely related to Parapedobacter lycopersici KACC 18788 T with 94.26 % similarities. The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) values between them and the validly published Parapedobacter species were all below the thresholds for delineating species, supporting that they were novel species of genus Parapedobacter . The ANI, AAI and dDDH values between strains C3-1-R+6 T and Parapedobacter lycopersici KACC 18788 T were 72, 75, and 18% respectively. Meanwhile, the ANI/AAI and dDDH values between these five isolates were higher than the threshold values, showing that they belonged to the same species of Parapedobacter . According to genome comparison, the novel isolates have some special biosynthetic gene clusters of secondary metabolites including bacteriton, aryl-polyene, lantipeptide and t1pks, which were absent from their most related phylogenetic neighbours P. lycopersici KACC 18788 T and P. pyrenivorans CGMCC 1.12195 T . The main polar lipids contained phosphatidylethanolamine, one unidentified phospholipid, one unidentified aminolipid, one unidentified glycolipid and five unidentified lipids. The predominant respiratory quinone was MK-7. The major cellular fatty acids were iso-C 15 : 0 , summed feature 3 (C 16 : 1  ω 7 c and/or C 16 : 1  ω 6 c ) and iso-C 17 : 0 3-OH. The genome size of strain C3-1-R+6 T was 5 984 948 bp, and its genomic DNA G+C content was 46.21 mol%. To sum up, the five strains were identified as a novel species of the genus Parapedobacter , for which the name Parapedobacter tibetensis sp. nov. was proposed. The type strain was C3-1-R+6 T (=CGMCC 1.19194 T =KCTC 92150 T ).

Platinum drugs, as a class of widely used chemotherapy agents, frequently appear in the treatment of cancer at different phrases. However, platinum resistance is the major bottleneck of platinum drugs for exerting anti-tumor effect. At present, the mechanism of platinum resistance has been thoroughly explored in terms of drug delivery methods, DNA damage repair function, etc., but it has not yet been translated into an effective weapon for reversing platinum resistance. Recently, autophagy has been proved to be closely related to platinum resistance, and the involved molecular mechanism may provide a new perspective on platinum resistance. The aim of this review is to sort out the studies related to autophagy and platinum resistance, and to focus on summarizing the relevant molecular mechanisms, so as to provide clues for future studies related to autophagy and platinum resistance., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Two Gram-stain-negative, strictly aerobic, rod-shaped, non-motile and non-gliding bacteria, designated as XJ19-10 T and XJ19-11, were isolated from river water in Xinjiang Uygur Autonomous Region, PR China. Cells of these strains were catalase-, oxidase- and gelatinase-positive and contained carotenoids but no flexirubins. Growth occurred at 10-30 °C, pH 7.0-9.0 and with 0-2.5% (w/v) NaCl. On the basis of the results of 16S rRNA gene sequence and genome analyses, the two isolates represented members of the genus Aquiflexum , and the closest relative was Aquiflexum aquatile Z0201 T with 16S rRNA gene sequence pairwise similarities of 97.9-98.1%. Furthermore, the average nucleotide identities and digital DNA-DNA hybridization identities between the two isolates and other relatives were all less than 82.9 and 28.2 %, respectively, all below the species delineation thresholds. The results of pan-genomic analysis indicated that the type strain XJ19-10 T shared 2813 core gene clusters with other three type strains of members of the genus Aquiflexum , as well as having 623 strain-specific clusters. The major polar lipids were phosphatidylethanolamine, phosphatidylcholine, an unidentified aminolipid and unidentified lipids. The predominant fatty acids (>10% of the total contents) were iso-C 15 : 0 , iso-C 15 : 1 G, iso-C 17 : 0 3-OH and summed feature 9, and MK-7 was the respiratory quinone. On the basis of the results of phenotypic, physiological, chemotaxonomic and genotypic characterization, strains XJ19-10 T and XJ19-11 are considered to represent a novel species, for which the name Aquiflexum gelatinilyticum sp. nov. is proposed. The type strain is XJ19-10 T (=CGMCC 1.19385 T =KCTC 92266 T ).

Homogeneous immunoassays represent an attractive alternative to traditional heterogeneous assays due to their simplicity and high efficiency. Homogeneous electrochemical assays, however, are not commonly accessed due to the requirement of electrode immobilization of the recognition elements. Herein, we demonstrate a new homogeneous electrochemical immunoassay based on the aggregation-collision strategy for the quantification of tumor protein biomarker alpha-fetoprotein (AFP). The detection principle relies on the aggregation of AgNPs induced by the molecular biorecognition between AFP and AgNPs-anti-AFP probes, which leads to an increased AgNP size and decreased AgNP concentration, allowing an accurate self-validated dual-mode immunoassay by performing nanoimpact electrochemistry (NIE) of the oxidation of AgNPs. The intrinsic one-by-one analytical capability of NIE as well as the participation of all of the atoms of the AgNPs in signal transduction greatly elevates the detection sensitivity. Accordingly, the current sensor enables a limit of detection (LOD) of 5 pg/mL for AFP analysis with high specificity and efficiency. More importantly, reliable detection of AFP in diluted human sera of hepatocellular carcinoma (HCC) patients is successfully achieved, indicating that the NIE-based homogeneous immunoassay shows great potential in HCC liquid biopsy.

Traumatic brain injury (TBI) survivors suffer from long-term disability and neuropsychiatric sequelae due to irreparable brain tissue destruction. However, there are still few efficient therapies to promote neurorestoration in damaged brain tissue. This study aimed to investigate whether the pro-oncogenic gene ski can promote neurorestoration after TBI. We established a ski-overexpressing experimental TBI mouse model using adenovirus-mediated overexpression through immediate injection after injury. Hematoxylin-eosin staining, MRI-based 3D lesion volume reconstruction, neurobehavioral tests, and analyses of neuronal regeneration and astrogliosis were used to assess neurorestorative efficiency. The effects of ski overexpression on the proliferation of cultured immature neurons and astrocytes were evaluated using imaging flow cytometry. The Ski protein level increased in the perilesional region at 3 days post injury. ski overexpression further elevated Ski protein levels up to 14 days post injury. Lesion volume was attenuated by approximately 36-55% after ski overexpression, with better neurobehavioral recovery, more newborn immature and mature neurons, and less astrogliosis in the perilesional region. Imaging flow cytometry results showed that ski overexpression elevated the proliferation rate of immature neurons and reduced the proliferation rate of astrocytes. These results show that ski can be considered a novel neurorestoration-related gene that effectively promotes neurorestoration, facilitates neuronal regeneration, and reduces astrogliosis after TBI., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Accumulating evidence has revealed the adenosine 2A receptor is a key tuner for neuropathological and neurobehavioral changes following traumatic brain injury by experimental animal models and a few clinical trials. Here, we highlight recent data involving acute/sub-acute and chronic alterations of adenosine and adenosine 2A receptor-associated signaling in pathological conditions after trauma, with an emphasis of traumatic brain injury, including neuroinflammation, cognitive and psychiatric disorders, and other severe consequences. We expect this would lead to the development of therapeutic strategies for trauma-related disorders with novel mechanisms of action., (Copyright © 2023. Published by Elsevier Inc.)

Two novel strains, designated XJ19-45 T and XJ19-1, were isolated from water of Kuche River in Xinjiang Uygur Autonomous Region, China. Their cells were Gram-stain-negative, aerobic and motile rods. The phylogenetic analyses based on 16S rRNA genes and genomes showed that the two isolates belonged to the genus Devosia and the closest relative was Devosia subaequoris HST3-14 T . The 16S rRNA genes sequences pairwise similarities, average nucleotide identities, digital DNA-DNA hybridizations and average amino acid identities between type strain XJ19-45 T and other relatives were all less than 98.3, 80.3, 23.6 and 85.7 %, respectively, all below the species delineation thresholds. Pan-genomic analysis indicated that the novel isolate XJ19-45 T shared 1594 core gene clusters with the 11 closely related type strains in Devosia , and the number of strain-specific clusters was 390. The major cellular fatty acids (>10 %) of the two isolates were summed feature 8, C 18 : 1 ω 7c 11-methyl and C 16 : 0 . Diphosphatidylglycerol, phosphatidylglycerol and glycolipids were the major polar lipids, and Q10 was the detected respiratory quinone. Based on the results of phenotypic, physiological, chemotaxonomic and genotypic characterizations, we propose that the isolates represent a novel species, for which the name Devosia ureilytica sp. nov. is proposed. The type strain is XJ19-45 T (=CGMCC 1.19388 T =KCTC 92263 T ).

Objective: To explore the early clinical efficacy of primary total hip arthroplasty(THA) with Corail standard stems (KS type) and high offset stems (KHO type), by analyzing the postoperative radiographic parameters of different offset of femoral components with Corail stem which has a neck-shaft angle of 135 ° in unilateral primary THA, by comparing the measurement results on both sides and analyzing the reconstruction of the postoperative femoral offset and the hip joint function recovery., Methods: A retrospective analysis was made of 186 patients with unilateral hip joint lesions who underwent the first total hip arthroplasty with Johnson & Johnson Corail prostheses from January 2015 to June 2017. According to the use of femoral prostheses with different eccentricities during the operation, the patients were divided into high eccentricity group and standard eccentricity group. In the high eccentricity group, there were 52 cases of Corail high eccentricity prosthesis(KHO type), including 20 females and 32 males;aged 21 to 71 years old with an average of(50.6±13.2) years;body mass index(BMI) was (26.0±4.1) kg/m 2 . The standard eccentricity group included 134 Corail standard femoral stem prostheses(KS type), 57 females and 77 males;aged 18 to 77 years old with an average of (47.3±14.0) years;BMI was (25.3±3.5) kg/m 2 . The abduction arm, femoral eccentricity, acetabular eccentricity and the length difference of lower limbs were measured on the postoperatively positive X-ray film of the hip joint. Harris score and related complications were recorded before and after the operation, and the stability of the prosthesis was analyzed., Results: There were significant differences in femoral eccentricity, joint eccentricity and abduction arm between the affected side and the healthy side in the high eccentricity group( P <0.05). There were significant differences in femoral eccentricity and acetabular eccentricity between the affected side and the healthy side in the standard eccentricity group( P <0.05). There were significant differences in combined eccentricity, abduction arm and length of lower limbs between two groups( P <0.05). In the high eccentricity group, the abduction arm of the affected hip joint was positively correlated with the femoral eccentricity, acetabular eccentricity and joint eccentricity( r =0.633, P <0.001; r =0.384, P =0.005; r =0.690, P <0.001). The same results were also obtained in the healthy side( r =0.688, P <0.001; r =0.574, P <0.001; r =0.765, P <0.001). In the standard eccentricity group, the abduction arm of the affected hip joint was positively correlated with the femoral eccentricity, acetabular eccentricity and combined eccentricity( r =0.734, P <0.001; r =0.418, P <0.001; r =0.749, P <0.001). The same results were also obtained in the healthy side( r =0.775, P <0.001; r =0.397, P <0.001; r =0.773, P <0.001). The difference of the length of both lower limbs was significantly correlated with the difference of bilateral joint eccentricity and bilateral abduction arm ( r =0.376, P =0.006; r =-0.346, P =0.012). There was no significant correlation between the difference of the length of both lower limbs and the difference of bilateral joint eccentricity and bilateral abduction arm ( r =-0.009, P =0.919; r =-0.036, P =0.682). There was no significant difference in Harris score between two groups at the last follow-up( P >0.05). At the last follow-up, Trendelenburg was negative in all patients in both groups, and the prostheses were stable., Conclusion: Both Corail standard stem and high offset stem may be effectively reconstruct the femoral offset, reconstruct the anatomical structure and biomechanics of the hip joint, and maintain the length of lower limbs and the stability of the hip joint in the unilateral primary total hip arthroplasty. Although the offset of the femur was not reconstructed normally in some cases, the stability of the components and postoperative function were not affected.