[Genetic analysis and PGT-SR outcome of a male carrier of exceptional complex chromosome rearrangement].

OBJECTIVE: To investigate the clinical and genetic characteristics of a male carrier of exceptional complex chromosome rearrangement (CCR) and the outcome of preimplantation genetic testing for chromosomal structural rearrangement (PGT-SR). METHODS: Using the modified high resolution G banding technique and whole-genome low-coverage sequencing (WGLCS), we analyzed the cellular karyotype and molecular karyotype of a male carrier of CCR, performed an analysis of the single-sperm chromosome copy number and conducted PGT-SR for the patient by next-generation sequencing (NGS). In addition, we reviewed the literature on reported male carriers of CCRs and summarized their normal/balanced sperm ratios and PGT-SR outcomes. RESULTS: The karyotype of the patient was 46,XY,der(5)inv(5)(q14.3q23.2)t(5;14;11) (q23.2;q31.1;q21),der(11)t(5;14;11);der(14)t(5;14;11), with the translocation breakpoints located in the intergenic region. Single-sperm sequencing revealed 20.0%（7/35）of normal haploids in the male's spermatozoa， and the results PGT-SR showed a proportion of 25.0%（4/16）of normal/balanced embryos. After thawing and transferring of 2 euploid blastocysts, a healthy male infant was successfully delivered. CONCLUSION: The proportion of normal haploids in the spermatozoa of male CCR carriers may be higher than theoretically predicted, and PGT-SR can effectively improve the pregnancy outcome in male CCR carriers and provide valuable data for genetic counseling.

In-situ construction of biomineralized cadmium sulfide-Rhodopseudomonas palustris hybrid system: Mechanism of synergistic light utilization.

Sulfide biomineralization is a microorganism-induced process for transforming the environmentally hazardous cadmium into useful resource utilization. This study successfully constructed cadmium sulfide nanoparticles-Rhodopseudomonas palustris (Bio-CdS NPs-R. palustris) hybrids. For the self-assembling hybrids, Bio-CdS NPs were treated as new artificial-antennas to enhance photosynthesis, especially under low light (LL). Bacterial physiological results of hybrids were significantly increased, particularly for cells under LL, with higher enhancement photon harvesting ability. The enhancement included the pigment contents, and the ratio of the peripheral light-harvesting complex Ⅱ (LH2) to light-harvesting Ⅰ (1.33 ± 0.01 under LL), leading to the improvements of light-harvesting, transfer, and antenna conversion efficiencies. Finally, the stimulated electron chain of hybrids improved bacterial metabolism with increased nicotinamide adenine dinucleotide (NADH, 174.5% under LL) and adenosine triphosphate (ATP, 41.1% under LL). Furthermore, the modified photosynthetic units were induced by the up-regulated expression of fixK, which was activated by reduced oxygen tension of the medium for hybrids. fixK up-regulated genes encoding pigments (crt, and bch) and complexes (puf, pucAB, and pucC), leading to improved light-harvesting and transfer, and transform ability. This study provides a comprehensive understanding of the solar energy utilization mechanism of in-situ semiconductor-phototrophic microbe hybrids, contributing to further theoretical insight into their practical application.

Stability and biomineralization of cadmium sulfide nanoparticles biosynthesized by the bacterium Rhodopseudomonas palustris under light.

Cadmium (Cd) pollution is regarded as a potent problem due to its hazard risks to the environment, making it crucial to be removed. Compared to the physicochemical techniques (e.g., adsorption, ion exchange, etc.), bioremediation is a promising alternative technology for Cd removal, due to its cost-effectiveness, and eco-friendliness. Among them, microbial-induced cadmium sulfide mineralization (Bio-CdS NPs) is a process of great significance for environmental protection. In this study, microbial cysteine desulfhydrase coupled with cysteine acted as a strategy for Bio-CdS NPs by Rhodopseudomonas palustris. The synthesis, activity, and stability of Bio-CdS NPs-R. palustris hybrid was explored under different light conditions. Results show that low light (LL) intensity could promote cysteine desulfhydrase activities to accelerate hybrid synthesis, and facilitated bacterial growth by the photo-induced electrons of Bio-CdS NPs. Additionally, the enhanced cysteine desulfhydrase activity effectively alleviated high Cd-stress. However, the hybrid rapidly dissolved under changed environmental factors, including light intensity and oxygen. The factors affecting the dissolution were ranked as follows: darkness/microaerobic ≈ darkness/aerobic < LL/microaerobic < high light (HL)/microaerobic < LL/aerobic < HL/aerobic. The research provides a deeper understanding of Bio-CdS NPs-bacteria hybird synthesis and its stability in Cd-polluted water, allowing advanced bioremediation treatment of heavy metal pollution in water.

Biochar-immobilized Bacillus megaterium enhances Cd immobilization in soil and promotes Brassica chinensis growth.

Phosphate solubilizing bacteria (PSB) has been considered an environmental-friendly phosphate fertilizer without cadmium (Cd) input into soils, but its possibility of Cd fixation in soil needs to be explored. Since direct inoculation results in a rapid decline of the population and activity, we immobilized Bacillus megaterium with maize straw biochar (B-PSB) and investigated its feasibility in remediating Cd-contaminated soil. Pot experiments showed that the application of B-PSB significantly ameliorated the growth of Brassica chinensis under Cd stress, with a fresh weight increased by 59.08% compared to the Cd-control. B-PSB reduced Cd accumulation in Brassica chinensis by 61.69%, and promoted the uptake of P and N by 134.97% and 98.71% respectively. Microbial community analysis showed B-PSB recruited more plant growth-promoting bacteria in near-rhizosphere soil, which provides a favorable microenvironment for both PSB and crops. Column leaching experiments verified that B-PSB achieved the dissolution of stable P while fixing Cd. Batch tests further revealed that biochar served as a successful carrier facilitating the growth of B. megaterium and Cd immobilization. Given the widespread Cd contamination in agricultural soils, our results indicate that B-PSB is a promising soil amendment to secure food safety.

Subcortical Structural Alterations in Autism Spectrum Disorder Aged 12-18 Years Old / 中国医学影像学杂志

Purpose To explore the subcortical structure characteristics in autism spectrum disorder(ASD)aged 12-18 years old and the developmental characteristics of abnormal regions with age.Materials and Methods A total of 102 adolescents aged 12-18 years old meeting the diagnostic criteria for ASD in diagnostic and statistical manual,fifth edition and 42 gender and age matched typically developing controls were enrolled from March 2013 to January 2021 in Peking University Sixth Hospital.Structural magnetic resonance imaging scans were performed on all participants.The freeSurfer software was used to process the 3D T1 images of all participants and segment the subcortical regions.Covariance analysis was performed to compare the volumes of subcortical regions between the two groups.Analysis of variance and covariance were used to explore the developmental differences of brain regions with significant group differences within the ASD and control groups in the age groups of 12-13,14-15 and 16-18,as well as between the ASD and control groups in these age groups.Results Compared to the control group,the volumes of the right caudate,right pallidum,left hippocampus,and corpus callosum anterior region were significantly increased in the ASD group(F=4.522,5.955,7.191,5.326,P<0.05).The volume of the corpus callosum anterior region showed significant differences among the aged 12-13,14-15 and 16-18 years groups of the control group(F=5.248,P=0.01),while there was no significant difference among these three groups of the ASD group(F=2.345,P=0.101).Conclusion Adolescents with ASD aged 12-18 years show abnormalities in multiple subcortical structures,and the developmental characteristics of the corpus callosum anterior region are different from typically developing controls,suggesting that the brains of adolescents with ASD have distinct developmental features.

P38MAPK/NF-κB-based study of the molecular mechanism of miR-146a intervention in septic cardiomy-opathy / 实用医学杂志

Objective An exploration of the molecular mechanism of microRNA-146a(miR-146)inter-vention in Sepsis-induced cardiomyopathy(SIC)using P38MAPK/NF-κB.Methods SD rats were divided into four groups by the random number table method:the normal control group,the SIC model group,the miR-146a agonist group,and the miR-146a inhibitor group.Rats in the normal control group and SIC model group were injected intraperitoneally with 0.2 μL/g saline,rats in the miR-146a agonist group were injected intraperitoneally with 0.2 μL/g miR-146a agonist,rats in the miR-146a inhibitor group were injected intraperitoneally with 0.2 μL/g miR-146a inhibitor;24 h later,rats in the SIC model group,miR-146a agonist group,and miR-146a inhibitor group were injected intraperitoneally with lipopolysaccharide(LPS)to prepare the SIC rat model,and the normal control group was injected with an equal amount of saline.Histopathological morphology was observed by HE staining;apoptosis rate of cardiomyocytes was detected by TUNEL;cardiac troponin I(cTnI)and B-type brain natriuretic peptide(BNP)contents were detected by ELISA;creatine kinase cardiac muscle binding(CK-MB)and myoglobin(Mb)contents were detected by chemiluminescence;p38 mitogen activation in rat myocardial tissue was detected by Western blot protein kinase(p38MAPK),nuclear factor-kB(NF-κB),tumor necrosis factor-α(TNF-α)and intercellular adhesion molecule-1(ICAM-1)by Western-Blot;miR-146a,TNF-α,interleukin-1α(IL-1α)and interleukin-1β(IL-1β)mRNA by reverse transcription quantitative(RT-q)PCR.Results Myocardial cells in the normal control group were uniform in size,neatly arranged,with distinct transverse lines,and had normal structure;myocardial cells in the SIC model group and miR-146a inhibitor group were disordered,with myocardial fibers fragmented and expanded at intervals.Myocardial structural damage was minimized in the miR-146a agonist group compared to the SIC model group.Compared with the normal control group,the apoptosis rate,serum cTnI,BNP,CK-MB,Mb levels,myocardial tissue p-p38 MAPK,p-NF-κB p65,TNF-α,ICAM-1 protein expression levels,TNF-α,IL-1α,miR-146a mRNA levels were significantly higher in the SIC model group,miR-146a agonist group and miR-146a inhibitor group,IL-1β mRNA levels were significantly increased and miR-146a mRNA levels were decreased.Compared with the SIC model group,the apoptosis rate,serum cTnI,BNP,CK-MB,Mb levels,myocardial tissue p-p38 MAPK,p-NF-κB p65,TNF-α,ICAM-1 protein expression in the miR-146a agonist group of rats levels,TNF-α,IL-1α,IL-1β mRNA levels were significantly reduced,and miR-146a mRNA levels were increased.Conclusion miR-146a has the ability to modulate the p38 MAPK/NF-κB signaling axis and the release of inflammatory factors.High miR-146a expression has some negative influence on the inflammatory response,reducing the onset and development of the inflammatory response while improving it.It can offer SIC early interven-tion therapy with a pre-study mechanism and theoretical support.

Changes of retinal nerve fiber layer thickness in patients with pseudoexfoliation glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the retinal nerve fiber layer(RNFL)thickness in Uyghur patients with pseudoexfoliation syndrome(PEX)or pseudoexfoliative glaucoma(PEXG)and to provide a theoretical basis for the early diagnosis of PEXG.METHODS: A retrospective case-control study was conducted. A total of 70 cases(70 eyes)of Uyghur PEX patients, 80 cases(80 eyes)of PEXG patients, and 60 cases(60 eyes)of age-related cataract patients who were admitted to our hospital from April 2018 to June 2020 were selected as the PEX group, PEXG group, and CON group, respectively. The PEXG group was further divided into mild-to-moderate stage(56 eyes)and severe stage(24 eyes)based on the stage of visual field defect, and the RNFL thickness at different locations of the optic disc was analyzed.RESULTS: The mean defect(MD)gradually increased in the CON group, PEX group, and PEXG group, and it was significantly higher in PEXG group than that in the PEX group(P&#x003C;0.01). The RNFL thickness at different locations of the optic disc in the PEX group, mild-to-moderate stage PEXG group, and severe-stage PEXG group was thinner than that in the CON group(all P&#x003C;0.01). The mean RNFL thickness, as well as the RNFL thickness below and above the optic disc, were lower in the PEX group than in the CON group(all P&#x003C;0.01). The RNFL thickness at all locations of the optic disc in the severe-stage PEXG group was significantly lower than that in the mild-to-moderate stage PEXG group(all P&#x003C;0.01).CONCLUSION: The RNFL thickness in Uyghur patients with PEX begins to be thinner than those without pseudoexfoliation syndrome, and early detection of RNFL thickness in PEX patients is helpful for the diagnosis and early treatment of PEXG.

Risk factor analysis of patients with biochemical recurrence after radical prostatectomy / 中华泌尿外科杂志

Objective:To investigate the risk factors for biochemical recurrence after radical prostatectomy.Methods:The clinical data of 558 radical prostatectomy patients admitted to the First Affiliated Hospital of Air Force Military Medical University from January 2010 to December 2020 were retrospectively analyzed. The average age was 67.9 (40-87) years old, and the average body mass index was 24.56 (15.12-35.94) kg/m 2. The average PSA was 41.07 ng/ml, including 48 cases<10 ng/ml, 98 cases 10-20 ng/ml, and 412 cases>20 ng/ml. There were 123, 214, 118, 89, and 14 cases with biopsy Gleason 6-10 score, respectively. The clinical stage : 90 cases in ≤T 2b, 273 cases in T 2c, and 195 cases in ≥T 3 . 558 cases underwent radical prostatectomy, including 528 robotic-assisted laparoscopic surgery, 25 laparoscopic surgery, and 5 open-surgery. The risk factors for postoperative biochemical recurrence were analyzed by Cox regression. Results:A total of 63 patients had postoperative pathological stage pT 2a, 32 patients had pT 2b, 241 patients had pT 2c, and 222 patients had ≥pT 3. A total of 210 cases developed biochemical recurrence after surgery, and the mean time to biochemical recurrence was 33.3 (3-127) months after the radical prostatectomy. The biochemical recurrence rates at 1, 3, and 5 years were 9.7% (54/558), 21.5% (120/558), and 31.7% (177/558), respectively. Among pT 2a and pT 2b patients, 7 (11.1%) and 4 (12.5%) cases developed biochemical recurrence, respectively. Among pT 2c stage patients, 145 (60.17%) cases had positive cut margins, treated with androgen-deprivation therapy (ADT) after surgery. 68 (28.21%) cases of pT 2c stage patients had biochemical recurrence at mean 36.1 (3-106)months after the radical prostatectomy. Among ≥pT 3 patients, 147 patients with positive margins, perineural invasion, seminal vesicle invasion and positive pelvic lymph nodes were treated with postoperative androgen deprivation therapy (ADT) + radiotherapy. 98 of 147 patients (66.67%) had biochemical recurrence, and the average time to biochemical recurrence was 30.6 (24-98) months.75 patients of ≥pT 3 without positive margins, perineural invasion, seminal vesicle invasion or positive pelvic lymph nodes, were treated with postoperative ADT. 33 of them (44%) had biochemical recurrence, and the average time to biochemical recurrence was 32.5 (21-106) months. 5-and 10-year survival rates of 210 patients with biochemical recurrence were 89.05% (187/210) and 78.09% (164/210) respectively, 5- and 10-year tumor-specific survival rates were 92.57% and 87.69%, respectively. 46 of 210 cases died, of which 31 (67.39%) died from prostate cancer, and 15 cases (32.61%) died from cardiovascular and cerebrovascular diseases. Multifactorial Cox regression analysis showed that patient's age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7 were independent risk factors for biochemical recurrence. Conclusions:After radical prostatectomy, patients were treated according to their pathological stage and surgical margins. Patients with positive margins have a higher risk of biochemical recurrence. The independent risk factors for biochemical recurrence included age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7.

A proof of concept for neutralizing antibody-guided vaccine design against SARS-CoV-2.

Mutations and transient conformational movements of the receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To mitigate viral escape, we developed a cocktail of neutralizing antibodies (NAbs) targeting epitopes located on different domains of spike (S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting the N-terminal domain (NTD) and RBD domain of S, effective at nM concentrations. Remarkably, a combination of RBD-targeting NAbs and NTD-binding NAbs, FC05, enhanced the neutralization potency in cell-based assays and an animal model. Results of competitive surface plasmon resonance assays and cryo-electron microscopy (cryo-EM) structures of antigen-binding fragments bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in the NTD and RBD of S, when immunized in rabbits and macaques, elicited potent protective immune responses against SARS-CoV-2. More importantly, two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection. These results provide a proof of concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD.

Establishment of a resource recycling strategy by optimizing isobutanol production in engineered cyanobacteria using high salinity stress.

BACKGROUND: Isobutanol is an attractive biofuel with many advantages. Third-generation biorefineries that convert CO2 into bio-based fuels have drawn considerable attention due to their lower feedstock cost and more ecofriendly refining process. Although autotrophic cyanobacteria have been genetically modified for isobutanol biosynthesis, there is a lack of stable and convenient strategies to improve their production. RESULTS: In this study, we first engineered Synechococcus elongatus for isobutanol biosynthesis by introducing five exogenous enzymes, reaching a production titer of 0.126 g/L at day 20. It was then discovered that high salinity stress could result in a whopping fivefold increase in isobutanol production, with a maximal in-flask titer of 0.637 g/L at day 20. Metabolomics analysis revealed that high salinity stress substantially altered the metabolic profiles of the engineered S. elongatus. A major reason for the enhanced isobutanol production is the acceleration of lipid degradation under high salinity stress, which increases NADH. The NADH then participates in the engineered isobutanol-producing pathway. In addition, increased membrane permeability also contributed to the isobutanol production titer. A cultivation system was subsequently developed by mixing synthetic wastewater with seawater to grow the engineered cyanobacteria, reaching a similar isobutanol production titer as cultivation in the medium. CONCLUSIONS: High salinity stress on engineered cyanobacteria is a practical and feasible biotechnology to optimize isobutanol production. This biotechnology provides a cost-effective approach to biofuel production, and simultaneously recycles chemical nutrients from wastewater and seawater.

Selenium nanoparticles ameliorate Brassica napus L. cadmium toxicity by inhibiting the respiratory burst and scavenging reactive oxygen species.

Cadmium (Cd) is a widely distributed soil contaminant which induces oxidative damage and is therefore toxic to plants. Although selenium oxyanions such as selenite (SeO32-) and selenate (SeO42-) can alleviate Cd stress to plants, it is not known whether selenium nanoparticles (SeNPs) are able to do the same. The present study demonstrated the positive impact of both SeNPs and SeO32- on Brassica napus L. growth under conditions of Cd stress. Underlying mechanisms were elucidated using an oxidative stress detection assay, whole-genome RNA sequencing, and RT-qPCR. Application of selenium, especially in the form of SeNPs, decreased Cd-induced reactive oxygen species production by inhibiting the expression of NADPH oxidases (BnaRBOHC, BnaRBOHD1, and BnaRBOHF1) and glycolate oxidase (BnaGLO), thereby decreasing oxidative protein and membrane lipid damage. In addition, SeNPs improved resistance to Cd stress by decreasing Cd accumulation, maintaining intracellular calcium homeostasis, promoting disulfide bond formation, and restoring the waxy outer layer of the leaf surface. Although both forms of selenium decreased Cd toxicity, the beneficial concentration range was more extensive for SeNPs than for SeO32-.

Preoperative PSMA PET-CT guidance for patients with high-risk prostate cancer and its effect on postoperative positive margin / 中华泌尿外科杂志

Objective:To explore the preoperative 68Ga-PSMA PET/CT examination on the guidance of surgical strategies for high-risk prostate cancer patients and the influence of positive surgical margins after surgery. Methods:The clinical data of 118 patients with high-risk prostate cancer who underwent robot-assisted laparoscopic radical prostatectomy from June 2019 to December 2020 in Xijing Hospital of Air Force Military Medical University was retrospectively analyzed. 47 patients received 68Ga-PSMA PET/CT examination before surgery (study group), and 71 cases without 68Ga-PSMA PET/CT examination before operation ( control group). There was no statistically significant difference in the age [69 (63, 76) vs. 67 (64, 74) years], PSA [PSA≤20ng/ml: 9.91 (6.00, 13.67) vs. 11.64 (8.15, 15.44) ng/ ml, PSA> 20ng/ml: 66.53 (53.66, 195.30) vs. 63.18 (30.08, 148.05) ng/ml], preoperative clinical staging (T 2/≥T 3: 21/26 cases vs. 34/37 cases), and Gleason score [8 (7, 9) vs. 8 (7, 9) points] (all P>0.05) between study group and control group. Both groups underwent robot-assisted laparoscopic radical prostatectomy. The surgical plan was based on the PSMA PET/CT and MRI results in study group and control group respectively. First, ensure that all tumors are removed, and secondly, preserve the patient's urethral length as much as possible to ensure postoperative urinary control.If there is seminal vesicle invasion, expand the scope of resection as needed. If lymph node metastasis is shown, lymph node dissection is performed. For those with negative lymph nodes in imaging studies, if enlarged lymph nodes are found during the operation, lymph node dissection is also performed. After the operation, the perioperative results and surgical margins of the two groups were compared, and the correlation between the PSA value and the SUVmax value of prostate cancer tissue was analyzed. Results:The operations of the two groups were successfully completed, and there was no transfer to open surgery. The operation time of the study group was shorter than that of the control group [175 (155, 205) min vs. 205 (155, 235) min, P=0.003], and the positive rate of resection margin was significantly lower than that of the control group [23.40% (11/47) vs. 45.07%(32/71), P=0.017]. For patients with pathological stage ≥pT 3, the positive rate of surgical margins in the study group was significantly lower than that in the control group [30.77%(8/26) vs. 62.16%(23/37), P=0.014]. In the study group, 11 cases of PSMA-PET showed positive lymph nodes before operation, 10 cases were pathologically positive after operation (90.91%). PSMA-PET showed negative lymph nodes in 1 case, which was pathologically positive after operation. In the control group, 26 cases underwent lymph node dissection, and 16 cases (61.54%) were pathologically positive after operation. The preoperative PSA value of 47 cases in the study group was positively correlated with the SUVmax value of prostate cancer tissue ( r=0.579, P<0.01). Conclusions:Preoperative 68Ga-PSMA PET/CT for high-risk prostate cancer patients can guide the surgeon to optimize the surgical plan, reduce the positive rate of resection margins, and effectively remove the metastatic lymph nodes, which will benefit the patients.

Risk factors for early neurological complications after revascularization in adult patients with moyamoya disease / 中华麻醉学杂志

Objective:To identify the risk factors for early neurological complications after revascularization in adult patients with moyamoya disease.Methods:The medical records of patients of both sexes with moyamoya disease, aged 18-65 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, who underwent revascularization in our hospital from January 2017 to June 2019, were retrospectively collected.According to the occurrence of early postoperative neurological complications, patients were divided into early postoperative neurological complication group and non-early postoperative neurological complication group.The factors such as patient′s age, gender, preoperative clinical symptoms, previous history of hypertension, history of diabetes, history of coronary heart disease, American Society of Anesthesiologists physical status, methods of anesthesia, type of operation, anesthesia time, time for start of operation, operation time, intraoperative urine volume, times of intraoperative vasoactive drugs used, and time of the post-anaesthesia observation room (PACU) stay were collected.Logistic regression analysis was used to identify the risk factors for postoperative early neurological complications.Results:A total of 510 adult patients with moyamoya disease underwent revascularization were enrolled in this study, and the incidence of early postoperative neurological complications was 9.0%.The results of logistic regression analysis showed that preoperative ischemia, intraoperative use of vasoactive drugs more than 3 times and PACU stay time>90 min were risk factors for postoperative neurological complications ( P<0.05). Conclusion:Preoperative ischemia, intraoperative use of vasoactive drugs >3 times and PACU stay time>90 min are risk factors for early neurological complications after revascularization in the patients with moyamoya disease.

Gut microbiota-mediated tributyltin-induced metabolic disorder in rats.

Tributyltin (TBT), an environmental pollutant widely used in antifouling coatings, can cause multiple-organ toxicity and gut microbiome dysbiosis in organisms, and can even cause changes in the host metabolomic profiles. However, little is known about the underlying effects and links of TBT-induced metabolic changes and gut microbiome dysbiosis. In this study, rats were exposed to TBT at a dose of 100 µg kg-1 body weight (BW) for 38 days, followed by multi-omics analysis, including microbiome, metabolomics, and metallomics. Results showed that TBT exposure reduced rat weight gain and decreased the serum triglyceride (TG) level. Metabolic analysis revealed that TBT fluctuated linoleic acid metabolism and glycerophospholipid metabolism in the liver; the tricarboxylic acid cycle (TCA cycle), nicotinate and nicotinamide metabolism, and arachidonic acid metabolism in serum; glycine, serine, and threonine metabolism, the one carbon pool by folate, nicotinate, and nicotinamide metabolism; and tryptophan metabolism in feces. Furthermore, TBT treatment dictated liver inflammation due to enhancing COX-2 expression by activating protein kinase R-like ER kinase (PERK) and C/EBP homologous protein (CHOP) to induce endoplasmic reticulum (ER) stress instead of stimulating arachidonic acid metabolism. Meanwhile, alteration of the intestinal flora [Acetivibrio]_ethanolgignens_group, Acetatifactor, Eisenbergiella, Lachnospiraceae_UCG-010, Enterococcus, Anaerovorax, and Bilophila under TBT exposure were found to be involved in further mediating liver inflammation, causing lipid metabolism abnormalities, such as TG, linoleic acid, and glycerophospholipids, and interfering with the energy supply process. Among these, [Acetivibrio]_ethanolgignens_group, Enterococcus, and Bilophila could be considered as potential biomarkers for TBT exposure based on receiver operator characteristic (ROC) curve analysis.

Intervention effect of seven-step exercise rehabilitation combined with elastic band resistance training on functional fitness and cardiovascular adverse events in patients with coronary heart disease / 中国医师杂志

Objective:To investigate the effects of seven-step exercise rehabilitation combined with elastic resistance training on functional fitness and cardiovascular adverse events in patients with coronary heart disease (CHD).Methods:116 patients with CHD in our hospital from March 2017 to March 2019 were selected for prospective study, and they were divided into observation group ( n=58) and control group ( n=58) according to the order of admission time. The control group was given routine intervention, and the observation group was given seven step exercise rehabilitation combined with elastic band resistance training on the basis of the control group. The intervention satisfaction, incidence of cardiovascular adverse events, functional physical fitness indexes, cardiac function [left ventricular ejection fraction (LVEF), cardiac stroke volume (SV), cardiac index (CI)] and activities of daily living (BI) were compared between the two groups. Results:After intervention, the aerobic endurance, limb flexibility, lower extremity muscle strength and upper limb muscle strength were better than those in the control group ( P<0.05). After intervention, the LVEF, CI, SV, daily behavior, physiology and daily activities scores in the observation group were higher were higher than those of the control group ( P<0.05) . The intervention satisfaction of the observation group was 94.83%(55/58) , higher than that of the control group 79.31%(46/58) ( P<0.05); the incidence of cardiovascular adverse events in the observation group was 5.17%(3/58) and 10.34%(6/58) of the control group, with no statistically significant difference ( P>0.05). Conclusions:Seven-step exercise rehabilitation combined with elastic band resistance training can effectively improve the functional fitness and heart function of CHD patients, improve daily living ability and intervention satisfaction, and prevent cardiovascular adverse events.

Short-term outcome of laparoscopic surgery versus open surgery on colon carcinoma: A meta-analysis.

OBJECTIVE: The aim of this article is to compare the oncological outcomes of laparoscopic and open resection for colon cancer. METHOD: Search the publications on comparison the efficacy of laparoscopic surgery comparison with open surgery in treatment outcomes of colon cancer to May, 2018. After rigorous reviewing on quality, the data was extracted from eligible trials. All trials analyzed the summary hazard ratios (HRs) of the endpoints of interest, including intraoperative and postoperative outcomes. RESULTS: A total of 13 trials were met our inclusion criteria. With the pooled result of duration of surgery indicate that laparoscopic surgery was associated with a trend longer operate time (SMD = 0.58, 95% CI 0.17-0.99; P＝0.005) , shorter length of hospital stay (SMD = -0.57, 95% CI -1.00--0.15; P = 0.008) and postoperative hospital stay (SMD = -0.66, 95% CI -0.99--0.33; P = 0.0001) , less blood loss (SMD = -0.68, 95% CI -1.12--0.24; P = 0.002), shorter incision length (SMD = -4.61, 95% CI -5.79--3.43; P＜＝0.00001 and less wound infection (OR = 0.30, 95% CI 0.13-0.67; P = 0.004). However, there were no differences in the number of lymph nodes harvested (P = 0.17), ileus (P = 0.91), pulmonary infection (P = 0.22) and postoperative complications (P = 0.24) between the 2 groups. CONCLUSION: Laparoscopic surgery had similar intraoperative and postoperative recovery parameters to those of the patients in the open group. The patients treated with laparoscopic had a trend longer operate time, shorter hospital stays, less intra-operative blood loss, faster recovery and lower incidence of wound infection. Whether it can be expected to be a standardization operation method for colon carcinoma still need more random clinical trials to be verified.

PDZ Scaffold Protein CAL Couples with Metabotropic Glutamate Receptor 5 to Protect Against Cell Apoptosis and Is a Potential Target in the Treatment of Parkinson's Disease.

Targeting mGluR5 has been an attractive strategy to modulate glutamate excitotoxicity for neuroprotection. Although human clinical trials using mGluR5 negative allosteric modulators (NAMs) have included some disappointments, recent investigations have added several more attractive small molecules to this field, providing a promise that the identification of more additional strategies to modulate mGluR5 activity might be potentially beneficial for the advancement of PD treatment. Here, we determined the role of the interacting partner CAL (cystic fibrosis transmembrane conductance regulator-associated ligand) in mGluR5-mediated protection in vitro and in vivo. In astroglial C6 cells, CAL deficiency blocked (S)-3, 5-dihydroxyphenylglycine (DHPG)-elicited p-AKT and p-ERK1/2, subsequently prevented group I mGluRs-mediated anti-apoptotic protection, which was blocked by receptor antagonist 1-aminoindan-1, 5-dicarboxylic acid (AIDA), and PI3K or MEK inhibitor LY294002 or U0126. In rotenone-treated MN9D cells, both CAL and mGluR5 expressions were decreased in a time- and dose-dependent manner, and the correlation between these 2 proteins was confirmed by lentivirus-delivered CAL overexpression and knockdown. Moreover, CAL coupled with mGluR5 upregulated mGluR5 protein expression by inhibition of ubiquitin-proteasome-dependent degradation to suppress mGluR5-mediated p-JNK and to protect against cell apoptosis. Additionally, CAL also inhibited rotenone-induced glutamate release to modulate mGluR5 activity. Furthermore, in the rotenone-induced rat model of PD, AAV-delivered CAL overexpression attenuated behavioral deficits and dopaminergic neuronal death, while CAL deficiency aggravated rotenone toxicity. On the other hand, the protective effect of the mGluR5 antagonist MPEP was weakened by knocking down CAL. In vivo experiments also confirmed that CAL inhibited ubiquitination-proteasome-dependent degradation to modulate mGluR5 expression and JNK phosphorylation. Our findings show that CAL protects against cell apoptosis via modulating mGluR5 activity, and may be a new molecular target for an effective therapeutic strategy for PD.

Association of free fatty acids with anxiety and depression in elderly patients with chronic heart failure / 中华老年医学杂志

Objective To analyze whether free fatty acids(FFA)are associated with anxiety and depression in elderly patients with chronic heart failure(CHF).Methods A cross-sectional study was conducted in patients by using questionnaires.According to the Zung Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale(SDS),126 patients were divided into the depression group (n=94),non-depression group (n =32),and anxiety group (n =48),and non-anxiety group (n =78).The difference in FFA levels between the two groups was analyzed.Moreover,the association of FFA with anxiety and depression was analyzed Results The incidence of anxiety in elderly patients with CHF was 38.1％(48 cases),and the incidence of depression was 74.6％ (94 cases).FFA levels were higher in both the anxiety and depression groups than in the non-anxiety and non-depression groups [(559.9 ± 256.2)μmol/L vs.(393.8 ± 147.8) μmol/L,(573.8 ± 264.7)μmol/L vs.(483.2 ± 225.2)μmol/L,P＜0.05 and 0.01)].The FFA level was positively correlated with SAS and SDS in elderly patients with CHF(r=0.214 and 0.275,P＜0.05 and 0.01).Multivariate regression analysis showed that the FFA level was a risk factor for elderly CHF patients with anxiety(β=0.074,95％CI:0.024～0.125,P=0.004)and depression(β=0.084,95％CI:0.022～0.145,P=0.008).Conclusions FFA levels are correlated with anxiety and depression in elderly patients with CHF.The FFA level is a risk factor for anxiety and depression in elderly patients with CHF.Psychological intervention should be carried out early in CHF patients with high levels of FFA to reduce the incidence of anxiety and depression.

Optimization of yeast autolysis under solid-state fermentation conditions / 生物工程学报

Yeast autolysis under solid-state fermentation can effectively promote the release of various active substances, thereby improving the quality of yeast products. The optimal process for yeast autolysis under solid-state fermentation was obtained by optimizing the autolysis temperature, autolysis time and the zinc ion concentration. We analyzed the indexes of free amino acid, soluble protein and α-amino nitrogen in the fermentation material, as well as A₂₆₀/A₂₈₀ ratio to determine yeast autolysis process conditions in the solid-state fermentation. On the basis of the obtained data, L₉ (3³) orthogonal test was designed to optimize the solid-state fermentation parameters for yeast autolysis: temperature at 40, 50 and 55 °C; time 12, 18 and 24 h; zinc ion concentration 2, 4 and 8 mg/kg. The optimum process conditions for yeast autolysis were: autolysis temperature 55 °C, time 18 h, zinc ion concentration 2 mg/kg, and soluble protein content reached 9.31 mg/g, free amino acid 14.36 mg/g, α-amino nitrogen 10.16 μg/g and A₂₆₀/A₂₈₀ 1.73. After optimization of the process, the soluble protein, free amino acid and α-amino nitrogen contents of the yeast autolysis production can be significantly increased, thereby obviously improving the quality of the composite culture.