Establishment and validation of the prediction model for postoperative delirium risk factors in older patients after total knee arthroplasty: A retrospective study.

This study aimed to establish an effective predictive model for postoperative delirium (POD) risk assessment after total knee arthroplasty (TKA) in older patients. The clinical data of 446 older patients undergoing TKA in the Orthopedics Department of our University from January to December 2022 were retrospectively analyzed, and the POD risk prediction model of older patients after TKA was established. Finally, 446 patients were included, which were divided into training group (n = 313) and verification group (n = 133). Logistic regression method was used to select meaningful predictors. The prediction model was constructed with nomographs, and the model was evaluated with correction curve and receiver operating characteristic curve. The logistic regression analysis showed that age, educational level, American Society of Anesthesiologists grade, accompaniment of chronic obstructive pulmonary disease, accompaniment of cerebral stroke, postoperative hypoxemia, long operation time, and postoperative pain were independent risk factors for POD after TKA (P < .05). The nomogram prediction model established. The area under receiver operating characteristic curve of the model group and the validation group were 0.954 and 0.931, respectively. The calibration curve of the prediction model has a high consistency between the 2 groups. The occurrence of POD was associated with age, educational level, American Society of Anesthesiologists grade, accompaniment of chronic obstructive pulmonary disease, accompaniment of cerebral stroke, postoperative hypoxemia, long operation time, and postoperative pain in TKA patients.

ABCC4 suppresses glioblastoma progression and recurrence by restraining cGMP-PKG signalling.

BACKGROUND: Cyclic nucleotides are critical mediators of cellular signalling in glioblastoma. However, the clinical relevance and mechanisms of regulating cyclic nucleotides in glioblastoma progression and recurrence have yet to be thoroughly explored. METHODS: In silico, mRNA, and protein level analyses identified the primary regulator of cyclic nucleotides in recurrent human glioblastoma. Lentiviral and pharmacological manipulations examined the functional impact of cyclic nucleotide signalling in human glioma cell lines and primary glioblastoma cells. An orthotopic xenograft mice model coupled with aspirin hydrogels verified the in vivo outcome of targeting cyclic nucleotide signalling. RESULTS: Elevated intracellular levels of cGMP, instead of cAMP, due to a lower substrate efflux from ATP-binding cassette sub-family C member 4 (ABCC4) is engaged in the recurrence of glioblastoma. ABCC4 gene expression is negatively associated with recurrence and overall survival outcomes in glioblastoma specimens. ABCC4 loss-of-function activates cGMP-PKG signalling, promoting malignancy in glioblastoma cells and xenografts. Hydrogels loaded with aspirin, inhibiting glioblastoma progression partly by upregulating ABCC4 expressions, augment the efficacy of standard-of-care therapies in orthotopic glioblastoma xenografts. CONCLUSION: ABCC4, repressing the cGMP-PKG signalling pathway, is a tumour suppressor in glioblastoma progression and recurrence. Aspirin hydrogels impede glioblastoma progression through ABCC4 restoration and constitute a viable translational approach.

Protective mechanism of rhubarb decoction against inflammatory damage of brain tissue in rats with mild hepatic encephalopathy： A study based on the PI3K/AKT/mTOR signaling pathway / 临床肝胆病杂志

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

Bottom-Up Synthesis of Multicompartmentalized Microreactors for Continuous Flow Catalysis.

The bottom-up assembly of biomimetic multicompartmentalized microreactors for use in continuous flow catalysis remains a grand challenge because of the structural instability or the absence of liquid microenvironments to host biocatalysts in the existing systems. Here, we address this challenge using a strategy that combines stepwise Pickering emulsification with interface-confined cross-linking. Our strategy allows for the fabrication of robust multicompartmentalized liquid-containing microreactors (MLMs), whose interior architectures can be exquisitely tuned in a bottom-up fashion. With this strategy, enzymes and metal catalysts can be separately confined in distinct subcompartments of MLMs for processing biocatalysis or chemo-enzymatic cascade reactions. As exemplified by the enzyme-catalyzed kinetic resolution of racemic alcohols, our systems exhibit a durability of 2000 h with 99% enantioselectivity. Another Pd-enzyme-cocatalyzed dynamic kinetic resolution of amines further demonstrates the versatility and long-term operational stability of our MLMs in continuous flow cascade catalysis. This study opens up a new way to design efficient biomimetic multicompartmental microreactors for practical applications.

Cellular and exosomal GPx1 are essential for controlling hydrogen peroxide balance and alleviating oxidative stress in hypoxic glioblastoma.

Tumor hypoxia promotes malignant progression and therapeutic resistance in glioblastoma partly by increasing the production of hydrogen peroxide (H2O2), a type of reactive oxygen species critical for cell metabolic responses due to its additional role as a second messenger. However, the catabolic pathways that prevent H2O2 overload and subsequent tumor cell damage in hypoxic glioblastoma remain unclear. Herein, we present a hypoxia-coordinated H2O2 regulatory mechanism whereby excess H2O2 in glioblastoma induced by hypoxia is diminished by glutathione peroxidase 1 (GPx1), an antioxidant enzyme detoxifying H2O2, via the binding of hypoxia-inducible factor-1α (HIF-1α) to GPx1 promoter. Depletion of GPx1 results in H2O2 overload and apoptosis in glioblastoma cells, as well as growth inhibition in glioblastoma xenografts. Moreover, tumor hypoxia increases exosomal GPx1 expression, which assists glioblastoma and endothelial cells in countering H2O2 or radiation-induced apoptosis in vitro and in vivo. Clinical data explorations further demonstrate that GPx1 expression was positively correlated with tumor grade and expression of HIF-1α, HIF-1α target genes, and exosomal marker genes; by contrast, it was inversely correlated with the overall survival outcome in human glioblastoma specimens. Our analyses validate that the redox balance of H2O2 within hypoxic glioblastoma is clinically relevant and could be maintained by HIF-1α-promoted or exosome-related GPx1.

Separation of Panax notoginseng saponins on modified rosin ester-bonded silica stationary phase and its mechanism.

A column prepared using a unique three-membered phenanthrene skeleton of rosin has complementary selectivity to a C18 column for some separation tasks. In this study, propylene pimaric acid (16-hydroxyethyl acrylate-34-n-butyl) ester (BRB) and propylene pimaric acid (16-hydroxyethyl acrylate-34-dodecyl) ester (BRLA) were used as functional ligands to prepare two novel stationary phases, namely BRB@SiO2 and BRLA@SiO2, through a "thiol-ene" click chemistry reaction. The characterization results of Fourier transform infrared spectroscopy, thermogravimetric analysis, nitrogen adsorption-desorption measurements, and contact angle tests showed that the BRB@SiO2 and BRLA@SiO2 stationary phases were successfully prepared. In addition, the performance of the columns was evaluated using the Tanaka test and hydrophobic subtraction model, which showed that the stationary phases exhibited typical reversed-phase chromatography performance and good hydrophobicity, hydrophobic selectivity, and steric selectivity. The changes in the retention of Panax notoginseng saponins on a column under different chromatographic conditions (acetonitrile content, flow rate, and column temperature) were investigated. The separation effect of BRB@SiO2 and BRLA@SiO2 columns on P. notoginseng saponins was better than that of the C18 column and the BRLA@SiO2 column could replace the C18 column for the detection of P. notoginseng saponins.

Hypoxia-induced CXC chemokine ligand 14 expression drives protumorigenic effects through activation of insulin-like growth factor-1 receptor signaling in glioblastoma.

Hypoxic tumor microenvironment (HTM) promotes a more aggressive and malignant state in glioblastoma. However, little is known about the role and mechanism of CXC chemokine ligand 14 (CXCL14) in HTM-mediated glioblastoma progression. In this study, we report that CXCL14 expression correlated with poor outcomes, tumor grade, and hypoxia-inducible factor (HIF) expression in patients with glioblastoma. CXCL14 was upregulated in tumor cells within the hypoxic areas of glioblastoma. Hypoxia induced HIF-dependent expression of CXCL14, which promoted glioblastoma tumorigenicity and invasiveness in vitro and in vivo. Moreover, CXCL14 gain-of-function in glioblastoma cells activated insulin-like growth factor-1 receptor (IGF-1R) signal transduction to regulate the growth, invasiveness, and neurosphere formation of glioblastoma. Finally, systemic delivery of CXCL14 siRNA nanoparticles (NPs) with polysorbate 80 coating significantly suppressed tumor growth in vivo and extended the survival time in patient-derived glioblastoma xenografts. Together, these findings suggest that HIF-dependent CXCL14 expression contributes to HTM-promoted glioblastoma tumorigenicity and invasiveness through activation of the IGF-1R signaling pathway. CXCL14 siRNA NPs as an oligonucleotide drug can inhibit glioblastoma progression and constitute a translational path for the clinical treatment of glioblastoma patients.

Design, Synthesis, and Molecular Docking Study of Novel 3-Cyanopyridine Derivatives for the Anti-Cancer Drug Target Survivin Protein.

Survivin is an important member of the antiapoptotic protein family and controls the cell's life cycle. Overexpression of survivin in tumor cells leads to inhibition of apoptosis, thus contributing to cancer cell proliferation. The largest binding pocket in the survivin dimer was located in the BIR domain. The key to the efficacy of 3-cyanopyridines was their surface interaction with the survivin amino acid Ile74. METHODS: Through the optimization of the 3-cyanopyridine, 29 new compounds with a 3- Cyanopyridine structure were designed, synthesized, and characterized by NMR, IR, and mass spectrometry. The antitumor activity of the compounds in vitro was detected by the MTT method. RESULTS: In vitro anti-tumor experiments showed that some compounds exhibited good anti-cancer effects. The IC50 values of the compound 2-amino-6-(2,4-difluorophenyl)-4-(4-hydroxyphenyl) nicotinonitrile (10n) against human liver cancer (Huh7), human glioma (U251), and human melanoma (A375) cells were 5.9, 6.0 and 7.2 µM, respectively. The IC50 values of the compound 6-(2,4-difluorophenyl)- 4-(4-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (9o) against Huh7, U251 and A375 cells were 2.4, 17.5 and 7.2 µM, respectively, which were better than those of 10- hydroxycamptothecin and 5-fluorouracil. Analysis of the results of molecular dynamics simulation established that the BIR domain is the optimal binding site on the survivin protein, and the fingerprints of the eight most active compounds and the molecular docking to the survivin protein are analyzed. CONCLUSION: 3-Cyanopyridine is an excellent backbone for antitumor lead compounds, 10n and 9o, as derivatives of 3-Cyanopyridine are excellent survivin protein-targeting inhibitors worthy of further study. The key factor in inhibiting survivin protein through the action of amino acid Ile74.

Mechanisms and research progress of targeted therapies on regulation of autophagy by natural compounds from traditional Chinese medicine / 药学学报

Autophagy is an important physiological process that can degrade cell components and maintain cell homeostasis, divided into three types including macroautophagy, microautophagy and chaperon-mediated autophagy generally, and macroautophagy is the most common form. Autophagy can affect the progression of a variety of diseases, such as cancer, neurodegenerative diseases, heart-related diseases, and autoimmune diseases, etc. However, autophagy can promote or inhibit diseases in different circumstances because of the dual roles of autophagy. Therefore, targeted regulating autophagy may be a potential treatment plan for diseases in specific stages of disease development. Now, with the development of traditional Chinese medicine (TCM) resources and the deepening of researches on the modern utilization of TCM, many active compounds from TCM have been discovered that can target autophagy to exert pharmacological activity. Most of the natural compounds activate or inhibit autophagy by affecting the classical PI3K/AKT/mTOR autophagy pathway. In addition, some compounds can also affect autophagy through MAPKs signaling pathways such as MEK/ERK, JNK and p38MAPK. These active compounds exert various biological activities by regulating autophagy, including anti-tumor, inhibiting neurodegenerative diseases, protecting cardiomyocytes, and relief of inflammatory response. In this review, we summarized the active compounds in TCM that affect autophagy by targeting different signaling pathways and their mechanisms of regulating autophagy, also introduced the effects of active compounds on diseases after affecting autophagy. Finally, this paper summarized and prospected the development of targeted autophagy for the treatment of diseases by TCM compounds, hoping to provide clues for subsequent exploration and research.

Investigation on blood lead level of workers in a lead-acid battery factory in Wuhan / 公共卫生与预防医学

Objective To investigate the occupational lead exposure and blood lead levels of workers in a lead-acid battery factory in Wuhan in 2020 and analyze the influencing factors of blood lead, and to provide reference for the blood lead intervention of the workers in the lead-acid battery factory. Methods The blood lead test results of 320 occupational lead-exposed workers in the factory were investigated and the influencing factors were analyzed. Results Among the 320 blood lead samples collected, 4 people had blood lead≥400 μg/L, accounting for 1.25%, and 89 people had blood lead≥200 μg/L, accounting for 27.81%. Among them, there were 235 males with a median blood lead of 155.10 μg/L, and 85 females with a median blood lead of 82.40 μg/L. The Wilcoxon rank sum test results of two independent samples showed that the overall blood lead level of male employees was higher than that of female employees, and the difference was statistically significant (P 50 years old. Using the Bonferroni method to adjust the significance level for pairwise comparison, it was found that there were significant differences in the blood lead concentrations between the group under 40 years old, the group of 40 - 50 years old, and the group of over 50 years old ( P < 0.016 after adjustment). The employees were classified into different workshops, including 38 samples from the administrative workshop , 40 samples from the charging workshop, and 242 samples from the assembly workshop. Using the Bonferroni method to adjust the significance level for pairwise comparison, it was found that the blood lead concentrations in the administrative workshop, the charging workshop, and the assembly workshop were statistically different ( P <0.016 after adjustment). Conclusion The age, gender, and type of work of the employees in the battery factory all have a certain impact on the blood lead level. It is necessary to continuously improve the management of the labor hygiene operation system and strengthen the self-protection level of the workers, and regularly carry out occupational hygiene inspection and health monitoring.

Tumoral calcinosis on thigh in a hemodialysis patient and literature review / 中华肾脏病杂志

The paper reported a patient under maintained hemodialysis for 11 years, with a large mass appeared in the right thigh after local injury. The mass was clinically considered as tumoral calcinosis combined with clinical, imaging and pathological findings. Several treatments such as enhancing dialysis adequacy, low calcium dialysate, calcimimetic agent, non-calcium- phosphorus binding agents, parathyroidectomy and intravenous infusion of sodium thiosulfate could not vanish the mass. Finally, the lump was surgically removed. The treatment of tumoral calcinosis in the hemodialysis patient can provide a instruction for similar situations in clinical practice.

Efficacy of lenalidomide in treatment of multiple myeloma and its effect on levels of regulatory T cells and natural killer cells of patients / 白血病·淋巴瘤

Objective:To investigate the clinical efficacy of lenalidomide combined with bortezomib and dexamethasone (RVd) regimen in treatment of newly diagnosed multiple myeloma (NDMM) patients and its effect on the levels of regulatory T cells (Treg cells) and natural killer (NK) cells.Methods:Thirty-eight NDMM patients who were admitted to the Second Affiliated Hospital of Bengbu Medical College from September 2019 to May 2022 were selected for a prospective study, and were divided into control group (18 cases) and observation group (20 cases) according to random number table method. The control group was treated with bortezomib+epirubicin+dexamethasone (VAd) regimen, and the observation group was treated with RVd regimen. The efficacy and safety were compared between the two groups. The levels of Treg cells (CD4 + CD25 + FOXP3 +) and NK cells (CD3 - CD56 + CD16 +) before and after treatment in the two groups were detected by flow cytometry, and the results were compared. Results:After 4 courses of treatment, the objective response rate (ORR) of the observation group was 95.0% (19/20), which was higher than that of the control group [77.8% (14/18)], and the difference was statistically significant ( P = 0.016). Before treatment, there was no statistical difference in the levels of Treg cells and NK cells between the two groups ( P values were 0.381 and 0.650). After treatment, the level of Treg cells in the control group increased from (1.5±0.5)% before treatment to (4.7±1.3)% ( P = 0.008), while the level of Treg cells in the observation group increased from (1.4±0.5)% before treatment to (6.8±1.5)% ( P = 0.001), and the level in the observation group was higher than that in the control group ( P = 0.027); the level of NK cells in the control group increased from (16±6)% before treatment to (20±5)% ( P = 0.004), while the level of NK cells in the observation group increased from (16±6)% before treatment to (24±6)% ( P = 0.006), and the level in the observation group was higher than that in the control group ( P = 0.032). The incidence rates of thrombocytopenia and neutropenia in the observation group were higher than those in the control group, and the differences were statistically significant ( P values were 0.012 and 0.027), which was reversible after active treatment. There was no statistical difference in the incidence rates of other adverse reactions (all P>0.05). Conclusions:RVd regimen for NDMM is clinically effective, safe and reliable, and the patients' levels of Treg cells and NK cells elevate after treatment.

Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B / 中南大学学报(医学版)

OBJECTIVES@#Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT).@*METHODS@#This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored.@*RESULTS@#Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910).@*CONCLUSIONS@#The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.

Epidemiological and etiological characteristics of active surveillance of foodborne illness / 公共卫生与预防医学

Objective To realize the epidemiological and pathogenic characteristics of foodborne illness in Shiyan in 2019 and provide targeted measures for the prevention and control work of the foodborne illness． Methods The active surveillance data of foodborne illness in shiyan in 2019 were collected and analyzed. The Salmonella strains isolated from the patients with foodborne illness were tested with serotyping，PFGE molecular classification and drug sensitivity test respectively according to《National foodborne illness surveillance workbook 2019》. Result A total of 3 191 cases of foodborne illness were analyzed. The pre-school children were the highest-risk group of foodborne diseases. Grain and grain product was the main suspicious contaminated food．The main location of eating place was family. A total of 330 samples were tested. The positive detection rate of foodborne illness was 20.30%（73/330）.The main pathogen were Rotavirus and Salmonella,and the detection rates were 11.21%(37/330) and 4.85%(16/330) respectively. The pre-school children were the group with the highest detection rate, which was 57.27% (63/110). The dominant serotype of the 14 Salmonella strains isolated from patients were Salmonella typhimurium and Salmonella enteritis. 14 different genotypes were obtained through PFGE classification and clustering. 64.29% (9/14) of Salmonella strains were multidrug-resistant strains. The drug resistance rates of ampicillin and tetracycline were the highest, which were 71.43%（11/14）and 64.29%（10/14）respectively. Conclusions The publicity and education of food safety should be strengthened and the surveillance network system of food-borne disease should be further improved according to the epidemiological and pathogenic characteristics of foodborne illness in Shiyan in 2019, and the use of clinical antibiotics should be controlled reasonably as well.

Genetic mechanism of adaptive evolution: the example of adaptation to high altitudes.

Since Darwin's time, elucidating the mechanism of adaptive evolution has been one of the most important scientific issues in evolutionary biology and ecology. Adaptive evolution usually means that species evolve special phenotypic traits to increase fitness under selective pressures. Phenotypic adaptation can be observed at different hierarchical levels of morphology, physiology, biochemistry, histology, and behavior. With the breakthroughs of molecular biology and next-generation sequencing technologies, mounting evidence has uncovered the genetic architecture driving adaptive complex phenotypes. Studying the molecular genetic mechanisms of evolutionary adaption will enable us to understand the forces shaping biodiversity and set up genotype-phenotype-environment interactions. Genetic bases of adaptive evolution have been explained by multiple hypotheses, including major-effect genes, supergenes, polygenicity, noncoding regions, repeated regions, and introgression. The strong selection pressure exerted by high-altitude extreme environments greatly promotes the occurrence of phenotypic and genetic adaptation in species. Studies on multi-omics data provide new insights into adaptive evolution. In this review, we systematically summarize the genetic mechanism of adaptive evolution, research progress in adaptation to high-altitude environmental conditions, and existing challenges and discuss the future perspectives, thereby providing guidance for researchers in this field.

N-doped pinecone-based carbon with a hierarchical porous pie-like structure: a long-cycle-life anode material for potassium-ion batteries.

Pinecone-based biomass carbon (PC) is a potential anode material for potassium-ion batteries because it is abundant, cheap, renewable, and easy to obtain. However, because of inferior kinetics and the effects of volume expansion due to the large radius of the K+ ion, it does not meet commercial performance requirements. In this study, nitrogen-doped PC (NPC) was prepared by carbonization in molten ZnCl2 with urea as a nitrogen source. A strategy based on synergistic effects between N doping and ZnCl2 molten salt was used to produce a hierarchically porous pie-like NPC with abundant defects and active sites and an enlarged interlayer distance-properties that enhance K+ adsorption, promote K+ intercalation/diffusion, and reduce the effects of volume expansion. This NPC exhibited a high reversible capacity (283 mA h g-1 at 50 mA g-1) and superior rate performance and cyclic stability (110 mA h g-1 after 1000 cycles at 5 A g-1), demonstrating its potential for use in potassium-ion batteries.

Haloperidol Instigates Endometrial Carcinogenesis and Cancer Progression by the NF-κB/CSF-1 Signaling Cascade.

Haloperidol is a routine drug for schizophrenia and palliative care of cancer; it also has antitumor effects in several types of cancer. However, the role of haloperidol in endometrial cancer (EC) development is still unclear. Here, we show that chronic haloperidol treatment in clinically relevant doses induced endometrial hyperplasia in normal mice and promoted tumor growth and malignancy in mice with orthotopic EC. The pharmacokinetic study indicated that haloperidol highly accumulated in the uterus of mice. In vitro studies revealed that haloperidol stimulated the cellular transformation of human endometrial epithelial cells (HECCs) and promoted the proliferation, migration, and invasion of human endometrial carcinoma cells (HECCs) by activating nuclear factor kappa B (NF-κB) and its downstream signaling target, colony-stimulating factor 1 (CSF-1). Gain of function of CSF-1 promotes the cellular transformation of HEECs and the malignant progression of HECCs. Moreover, blockade of CSF-1 inhibited haloperidol-promoted EC progression in vitro and in vivo. A population-based cohort study of EC patients further demonstrated that the use of haloperidol was associated with increased EC-specific mortality. Collectively, these findings indicate that clinical use of haloperidol could potentially be harmful to female patients with EC.

Potential millennial-scale avian declines by humans in southern China.

Mounting observational records demonstrate human-caused faunal decline in recent decades, while accumulating archaeological evidence suggests an early biodiversity impact of human activities during the Holocene. A fundamental question arises concerning whether modern wildlife population declines began during early human disturbance. Here, we performed a population genomic analysis of six common forest birds in East Asia to address this question. For five of them, demographic history inference based on 25-33 genomes of each species revealed dramatic population declines by 4- to 48-fold over millennia (e.g. 2000-5000 thousand years ago). Nevertheless, summary statistics detected nonsignificant correlations between these population size trajectories and Holocene temperature variations, and ecological niche models explicitly predicted extensive range persistence during the Holocene, implying limited demographic consequence of Holocene climate change. Further analyses suggest high negative correlations between the reconstructed population declines and human disturbance intensities and indicate a potential driver of human activities. These findings provide a deep-time and large-scale insight into the recently recognized avifaunal decline and support an early origin hypothesis of human effects on biodiversity. Overall, our study sheds light on the current biodiversity crisis in the context of long-term human-environment interactions and offers a multi-evidential framework for quantitatively assessing the ecological consequences of human disturbance.

Biocontrol potential of Burkholderia sp. BV6 against the rice blast fungus Magnaporthe oryzae.

AIM: To investigate the broad-spectrum antifungal activity of Burkholderia sp. BV6, that is isolated from rice roots and its biocontrol potential against rice blast caused by Magnaporthe oryzae. METHODS AND RESULTS: We evaluated the ability to isolate BV6 in the biological control of rice blast disease and investigated its antifungal mechanisms. BV6 strongly inhibited the hyphal growth of M. oryzae Guy11 and other plant pathogenic fungi, and pot experiments showed that BV6 significantly decreases the disease index of rice blast from 47.5 to 24.6. The secreted small-molecule secondary metabolites were regarded as weapons during the antifungal process by inhibiting the germination of M. oryzae conidia and mycelial growth, and thereby prevent the following infection. Liquid chromatography-mass spectrometry analysis of the metabolites from the supernatant of isolate BV6 showed that the antifungal weapons of isolate BV6 are novel, small, molecular hydrophilic compounds that are different from reported antifungal compounds. CONCLUSIONS: The isolate BV6 inhibits the M. oryzae infection by the production of small-molecule antifungal compounds. SIGNIFICANCE AND IMPACT OF THE STUDY: The current study discovers the role of the Burkholderia sp. BV6 in the biocontrol of plant pathogenic fungi. Therefore, isolate BV6 is a potential candidate for developing a microbial formulation for the biocontrol of the most common disease of rice blast.

Synthesis, antifungal activity and 3D-QSAR study of novel acyl thiourea compounds containing gem-dimethylcyclopropane ring.

A series of novel acyl thiourea compounds containing gem-dimethylcyclopropane ring were designed and synthesized by multi-step reactions in search of novel antifungal molecules. Structures of all the target compounds were characterized by spectral techniques of UV-vis, FT-IR, 1H-NMR, 13C-NMR, and ESI-MS. The antifungal activity of the target compounds was preliminarily evaluated by agar dilution method. The antifungal bioassay revealed that, at 50 µg/mL, compounds 5h (R = o-F), 5m (R = p-Br), and 5n (R = o-NO2) showed the same antifungal activity of 73.6% against Physalospora piricola, which was comparable than that of the positive control. Furthermore, against Gibberella zeae, compounds 5k (R = m-Cl), 5l (R = m-Br), 5m (R = p-Br), and 5n (R = o-NO2) displayed the same antifungal activity of 75.6%, and compound 5o (R = p-NO2) displayed antifungal activity of 78.8%, which were all better than that of the positive control. The preliminary analysis of 3D-QSAR model was performed to study the effect of molecular structure on biological activity using the comparative molecular field analysis (CoMFA) method. The results showed 3D-QSAR model (r2 = 0.995, q2 = 0.503) was reasonable and effective.