A permutable MLP-like architecture for disease prediction from gut metagenomic data.

Metagenomic data plays a crucial role in analyzing the relationship between microbes and diseases. However, the limited number of samples, high dimensionality, and sparsity of metagenomic data pose significant challenges for the application of deep learning in data classification and prediction. Previous studies have shown that utilizing the phylogenetic tree structure to transform metagenomic abundance data into a 2D matrix input for convolutional neural networks (CNNs) improves classification performance. Inspired by the success of a Permutable MLP-like architecture in visual recognition, we propose Metagenomic Permutator (MetaP), which applied the Permutable MLP-like network structure to capture the phylogenetic information of microbes within the 2D matrix formed by phylogenetic tree. Our experiments demonstrate that our model achieved competitive performance compared to other deep neural networks and traditional machine learning, and has good prospects for multi-classification and large sample sizes. Furthermore, we utilize the SHAP (SHapley Additive exPlanations) method to interpret our model predictions, identifying the microbial features that are associated with diseases.

The chromatin accessibility landscape of pistils and anthers in rice.

Transcription activation is tightly associated with the openness of chromatin and allows direct contact between transcriptional regulators and their targeted DNA for gene expression. However, there are limited studies on the annotation of open chromatin regions (OCRs) in rice (Oryza sativa), especially those in reproductive organs. Here, we characterized OCRs in rice pistils and anthers with an assay for transposase-accessible chromatin using sequencing. Despite a large overlap, we found more OCRs in pistils than in anthers. These OCRs were enriched in gene transcription start sites (TSSs) and showed tight associations with gene expression. Transcription factor (TF) binding motifs were enriched at these OCRs as validated by TF chromatin immunoprecipitation followed by sequencing. Pistil-specific OCRs provided potential regulatory networks by binding directly to the targets, indicating that pistil-specific OCRs may be indicators of cis-regulatory elements in regulating pistil development, which are absent in anthers. We also found that open chromatin of pistils and anthers responded differently to low temperature (LT). These data offer a comprehensive overview of OCRs regulating reproductive organ development and LT responses in rice.

Global, regional, and national burdens of myocarditis, 1990-2019: systematic analysis from GBD 2019 : GBD for myocarditis.

OBJECTIVES: Myocarditis, a health-threatening heart disease, is attracting increasing attention. This systematic study was conducted to study the prevalence of disease through the trends of incidence, mortality, disability-adjusted life years (DALYs) over the last 30 years, which would be helpful for the policymakers to better the choices for reasonable decisions. METHODS: The global, regional, and national burdens of myocarditis from 1990-2019 were analyzed by using the 2019 Global Burden of Disease (GBD) database. This study on myocarditis produced new findings according to age, sex, and Social-Demographic Index (SDI) by investigating DALYs, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and corresponding estimated annual percentage change (EAPC). RESULTS: The number of myocarditis incidence increased by 62.19%, from 780,410 cases in 1990 to 1,265,770 cases in 2019. The ASIR decreased by 4.42% (95%CI, from -0.26% to -0.21%) over the past 30 years. The number of deaths from myocarditis increased by 65.40% from 19,618 in 1990 to 324,490 in 2019, but the ASDR was relatively stable over the investigated period. ASDR increased in low-middle SDI regions (EAPC=0.48; 95%CI, 0.24 to 0.72) and decreased in low SDI regions (EAPC=-0.97; 95%CI, from -1.05 to -0.89). The age-standardized DALY rate decreased by 1.19% (95%CI, from -1.33% to -1.04%) per year. CONCLUSIONS: Globally, the ASIR and DALY for myocarditis decreased and the ASDR was stable over the past 30 years. The risk of incidences and death cases increased with age. Measures should be taken to control the risk of myocarditis in high-burden regions. Medical supplies should be improved in the high-middle SDI regions and middle SDI regions to reduce the deaths from myocarditis in these regions.

A Blue Light-Responsive Strong Synthetic Promoter Based on Rational Design in Chlamydomonas reinhardtii.

Chlamydomonas reinhardtii (C. reinhardtii) is a single-cell green alga that can be easily genetically manipulated. With its favorable characteristics of rapid growth, low cost, non-toxicity, and the ability for post-translational protein modification, C. reinhardtii has emerged as an attractive option for the biosynthesis of various valuable products. To enhance the expression level of exogenous genes and overcome the silencing of foreign genes by C. reinhardtii, synthetic promoters such as the chimeric promoter AR have been constructed and evaluated. In this study, a synthetic promoter GA was constructed by hybridizing core fragments from the natural promoters of the acyl carrier protein gene (ACP2) and the glutamate dehydrogenase gene (GDH2). The GA promoter exhibited a significant increase (7 times) in expressing GUS, over the AR promoter as positive control. The GA promoter also displayed a strong responsiveness to blue light (BL), where the GUS expression was doubled compared to the white light (WL) condition. The ability of the GA promoter was further tested in the expression of another exogenous cadA gene, responsible for catalyzing the decarboxylation of lysine to produce cadaverine. The cadaverine yield driven by the GA promoter was increased by 1-2 times under WL and 2-3 times under BL as compared to the AR promoter. This study obtained, for the first time, a blue light-responsive GDH2 minimal fragment in C. reinhardtii, which delivered a doubling effect under BL when used alone or in hybrid. Together with the strong GA synthetic promoter, this study offered useful tools of synthetic biology to the algal biotechnology field.

Analysis of gene expression in early seed germination of rice: landscape and genetic regulation.

BACKGROUND: Seed germination is a crucial process, which determines the initiation of seed plant life cycle. The early events during this important life cycle transition that called early seed germination is defined as initially water uptake plus radicle growing out of the covering seed layers. However, a specific genome-wide analysis of early seed germination in rice is still obscure. RESULTS: In this study, the physiological characteristics of rice seed during seed germination are determined to define key points of early seed germination. Transcriptome analyses of early phase of seed germination provided deeper insight into the genetic regulation landscape. Many genes involved in starch-to-sucrose transition were differentially expressed, especially alpha-amylase 1b and beta-amylase 2, which were predominantly expressed. Differential exon usage (DEU) genes were identified, which were significantly enriched in the pathway of starch and sucrose metabolism, indicating that DEU events were critical for starch-to-sucrose transition at early seed germination. Transcription factors (TFs) were also dramatic expressed, including the abscisic acid (ABA) responsive gene, OsABI5, and gibberellic acid (GA) responsive genes, GAI. Moreover, GAI transactivated GA responsive gene, GAMYB in vivo, indicating a potential pathway involved in early seed germination process. In addition, CBL-interacting protein kinase (CIPK) genes, such as CIPK13, CIPK14 and CIPK17 were potentially interacted with other proteins, indicating its pivotal role at early seed germination. CONCLUSION: Taken together, gene regulation of early seed germination in rice was complex and protein-to-gene or protein-to-protein interactions were indispensable.

OsTPP1 regulates seed germination through the crosstalk with abscisic acid in rice.

Seed germination is essential for direct seeding in rice. It has been demonstrated that trehalose-6-phosphate phosphatase 1 (OsTPP1) plays roles in improving yield and stress tolerance in rice. In this study, the roles of OsTPP1 on seed germination in rice were investigated. The tpp1 mutant germinated slower than the wild-type (WT), which can be restored by exogenous trehalose. tpp1 seeds showed higher ABA content compared with WT seeds. The tpp1 mutant was hypersensitive to ABA and ABA catabolism inhibitor (Dinicozanole). Furthermore, two ABA catabolism genes were downregulated in the tpp1 mutant which were responsible for increased ABA concentrations, and exogenous trehalose increased transcripts of ABA catabolism genes, suggesting that OsTPP1 and ABA catabolism genes acted in the same signaling pathway. Further analysis showed that a transcription factor of OsGAMYB was an activator of OsTPP1, and expression of OsGAMYB was decreased by both the exogenous and endogenous ABA, subsequently reducing the expression of OsTPP1, which suggested a new signaling pathway required for seed germination in rice. In addition, ABA-responsive genes, especially OsABI5, were invoved in OsTPP1-mediated seed germination. Overall, our study provided new pathways in seed germination that OsTPP1 controlled seed germination through crosstalk with the ABA catabolism pathway.

Comprehensive epigenome and transcriptome analysis of carbon reserve remobilization in indica and japonica rice stems under moderate soil drying.

Moderate soil drying (MD) imposed at the post-anthesis stage significantly improves carbon reserve remobilization in rice stems, increasing grain yield. However, the methylome and transcriptome profiles of carbon reserve remobilization under MD are obscure in indica and japonica rice stems. Here, we generated whole-genome single-base resolution maps of the DNA methylome in indica and japonica rice stems. DNA methylation levels were higher in indica than in japonica and positively correlated with genome size. MD treatment had a weak impact on the changes in methylation levels in indica. Moreover, the number of differentially methylated regions was much lower in indica, indicating the existence of cultivar-specific methylation patterns in response to MD during grain filling. The gene encoding ß-glucosidase 1, involved in the starch degradation process, was hypomethylated and up-regulated in indica, resulting in improved starch to sucrose conversion under MD treatment. Additionally, increased expression of MYBS1 transactivated the expression of AMYC2/OsAMY2A in both indica and japonica, leading to enhanced starch degradation under MD. In contrast, down-regulated expression of MYB30 resulted in increased expression of BMY5 in both cultivars. Our findings decode the dynamics of DNA methylation in indica and japonica rice stems and propose candidate genes for improving carbon reserve remobilization.

Intelligent diagnosis with Chinese electronic medical records based on convolutional neural networks.

BACKGROUND: Benefiting from big data, powerful computation and new algorithmic techniques, we have been witnessing the renaissance of deep learning, particularly the combination of natural language processing (NLP) and deep neural networks. The advent of electronic medical records (EMRs) has not only changed the format of medical records but also helped users to obtain information faster. However, there are many challenges regarding researching directly using Chinese EMRs, such as low quality, huge quantity, imbalance, semi-structure and non-structure, particularly the high density of the Chinese language compared with English. Therefore, effective word segmentation, word representation and model architecture are the core technologies in the literature on Chinese EMRs. RESULTS: In this paper, we propose a deep learning framework to study intelligent diagnosis using Chinese EMR data, which incorporates a convolutional neural network (CNN) into an EMR classification application. The novelty of this paper is reflected in the following: (1) We construct a pediatric medical dictionary based on Chinese EMRs. (2) Word2vec adopted in word embedding is used to achieve the semantic description of the content of Chinese EMRs. (3) A fine-tuning CNN model is constructed to feed the pediatric diagnosis with Chinese EMR data. Our results on real-world pediatric Chinese EMRs demonstrate that the average accuracy and F1-score of the CNN models are up to 81%, which indicates the effectiveness of the CNN model for the classification of EMRs. Particularly, a fine-tuning one-layer CNN performs best among all CNNs, recurrent neural network (RNN) (long short-term memory, gated recurrent unit) and CNN-RNN models, and the average accuracy and F1-score are both up to 83%. CONCLUSION: The CNN framework that includes word segmentation, word embedding and model training can serve as an intelligent auxiliary diagnosis tool for pediatricians. Particularly, a fine-tuning one-layer CNN performs well, which indicates that word order does not appear to have a useful effect on our Chinese EMRs.

Enhancing isobutyric acid production from engineered Acidithiobacillus ferrooxidans cells via media optimization.

The chemolithoautotrophic bacterium Acidithiobacillus ferrooxidans has previously been genetically modified to produce isobutyric acid (IBA) from carbon dioxide while obtaining energy from the oxidation of ferrous iron. Here, a combinatorial approach was used to explore the influence of medium composition in both batch and chemostat cultures in order to improve IBA yields (g IBA/mol Fe(2+)) and productivities (g IBA/L/d). Medium pH, ferrous concentration (Fe(2+)), and inclusion of iron chelators all had positive impact on the IBA yield. In batch experiments, gluconate was found to be a superior iron chelator because its use resulted in smaller excursions in pH. In batch cultures, IBA yields decreased linearly with increases in the final effective Fe(3+) concentrations. Chemostat cultures followed similar trends as observed in batch cultures. Specific cellular productivities were found to be a function of the steady state ORP (Oxidation-reduction potential) of the growth medium, which is primarily determined by the Fe(3+) to Fe(2+) ratio. By operating at low ORP, chemostat cultures were able to achieve volumetric productivities as high as 3.8 ± 0.2 mg IBA/L/d which is a 14-fold increase over the previously reported value.

Engineering the iron-oxidizing chemolithoautotroph Acidithiobacillus ferrooxidans for biochemical production.

There is growing interest in developing non-photosynthetic routes for the conversion of CO2 to fuels and chemicals. One underexplored approach is the transfer of energy to the metabolism of genetically modified chemolithoautotrophic bacteria. Acidithiobacillus ferrooxidans is an obligate chemolithoautotroph that derives its metabolic energy from the oxidation of iron or sulfur at low pH. Two heterologous biosynthetic pathways have been expressed in A. ferrooxidans to produce either isobutyric acid or heptadecane from CO2 and the oxidation of Fe(2+). A sevenfold improvement in productivity of isobutyric acid was obtained through improved media formulations in batch cultures. Steady-state efficiencies were lower in continuous cultures, likely due to ferric inhibition. If coupled to solar panels, the photon-to-fuel efficiency of this proof-of-principle process approaches estimates for agriculture-derived biofuels. These efforts lay the foundation for the utilization of this organism in the exploitation of electrical energy for biochemical synthesis.

[Effects of Scalp Acupuncture on Serum NSE and S-100ß Concentrations and Postoperative Cogni- tive Function of Elderly Patients Undergoing Hip Replacement].

OBJECTIVE: To explore the effect of Scalp acupuncture on serum neuron specific enolase (NSE) and S-100ß concentrations, and incidence rates of postoperative delirium (POD) and postoperative cognitive function (POCD) of elderly patients undergoing hip replacement. METHODS: Eighty-four patients undergoing scheduled hip replacement under combined spinal-epidural anesthesia (CSEA) were assigned to the control group (group C) and the scalp acupuncture group (group S) according to random digit table, 42 cases in each group. In group S, scalp acupuncture was additionally performed according to International Standardized Scheme for Scalp Acupuncture. Scalp acupuncture was performed during the operation from the MS1 middle line of forehead [1 cun before Shenting (GV24), including Shenting (GV24)] and MS5 middle line of vertex [from Baihui (DU20) to Qianding (DU21), including Baihui (DU20) and Qianding (DU21)]. The operation time and post-operative length of stay were observed. The midazolam dosage, hemorrhage amount, fluid transfusion amount, urine amount, use rates of ephedrine and atropine during the operation were also observed and compared between the two groups. The occurrence rate of POD and POCD at post-operative day 3 (T1), week 1 (T2), month 3 (T3), and month 6 (T4) were measured. Eighteen patients were randomly selected to collect blood from internal jugular vein before anesthesia t0), immediately after ending the surgery (t1), 6 h after operation (t2), 24 h after operation (t3), and 48 h after operation (t4), respectively. Serum levels of NSE and S-100ß were correspondingly measured. RESULTS: There was no statistical difference in the operation time, midazolam dosage used during the operation, hemorrhage amount, fluid transfusion amount, urine amount, use rates of ephedrine and atropine (P > 0.05). Compared with group C, the post-operative length of stay was shortened in group S (P < 0.05). The incidence rate of POD and that of POCD at each time point were lower in group S (P < 0.05). The expression level of NSE decreased at t2, t3, and t4, and the expression level of S100ß also decreased at t1, t2, t3, and t4(P < 0.05). There was no statistical difference in expression levels of NSE or S100ß between the two groups at other time points (P > 0.05). CONCLUSION: Scalp acupuncture could attenuate central nervous system lesion and improve POCD of elderly patients undergoing hip replacement.

Addition of citrate to Acidithiobacillus ferrooxidans cultures enables precipitate-free growth at elevated pH and reduces ferric inhibition.

Acidithiobacillus ferrooxidans is an acidophilic chemolithoautotroph that is important in biomining and other biotechnological operations. The cells are able to oxidize inorganic iron, but the insolubility and product inhibition by Fe(3+) complicates characterization of these cultures. Here we explore the growth kinetics of A. ferrooxidans in iron-based medium in a pH range from 1.6 to 2.2. It was found that as the pH was increased from 1.6 to 2.0, the maintenance coefficient decreased while both the growth kinetics and maximum cell yield increased in the precipitate-free, low Fe(2+) concentration medium. In higher iron media a similar trend was observed at low pH, but the formation of precipitates at higher pH (2.0) hampered cell growth and lowered the specific growth rate and maximum cell yield. In order to eliminate ferric precipitates, chelating agents were introduced into the medium. Citric acid was found to be relatively non-toxic and did not appear to interfere with iron oxidation at a maximum concentration of 70 mM. Inclusion of citric acid prevented precipitation and A. ferrooxidans growth parameters resumed their trends as a function of pH. The addition of citrate also decreased the apparent substrate saturation constant (KS ) indicating a reduction in the competitive inhibition of growth by ferric ions. These results indicate that continuous cultures of A. ferrooxidans in the presence of citrate at elevated pH will enable enhanced cell yields and productivities. This will be critical as these cells are used in the development of new biotechnological applications such as electrofuel production.

Psychotherapeutic and pharmacological agents for post-traumatic stress disorder with sleep disorder: network meta-analysis.

OBJECTIVE: The current guidelines and canonical norms of diagnosis or treatment for Post-traumatic stress disorder (PTSD) with sleep disorder are still conflicting and have not yet reached a consensus. This study aimed to unravel the most effective countermeasures between two categories (psychotherapy and pharmacotherapy) put forward by the National Institute for Health and Clinical Excellence (NICE) and World Federation of Societies of Biological Psychiatry (WFSBP) respectively to treat PTSD individuals co-exist with sleep disorders. METHODS: Four databases, including PubMed, EMBASE, Cochrane Library, and APA PsyNet, were searched from inception to February 02, 2023. RESULTS: Twenty articles with 24 Randomized controlled trials (RCTs) and a total number of 1,647 participants were included. As demonstrated in the network meta-analysis comparison results, CBT-I (standardized mean differences (SMD) = -1.51,95% confidence interval (CI):-2.55 to -0.47), CBT-I plus IRT (SMD = -1.71, 95%CI:-3.39, -0.03), prazosin (SMD = -0.87,95%CI:-1.59 to -0.16) and hydroxyzine (SMD = -1.06, 95%CI: -1.94 to -0.19) significantly reduced PTSD symptoms compared with placebo. In contrast to placebo, CBT-I (SMD = -5.61,95%CI:-8.82 to -2.40) significantly improved sleep quality. For nightmare severity, IRT (SMD =-0.65, 95%CI:-1.00 to -0.31), prazosin (SMD = -1.20,95%CI:-1.72 to -0.67) and hydroxyzine (SMD = -0.98,95%CI:-1.58 to -0.37) significantly reduced nightmare severity in comparison with placebo. CONCLUSIONS: This study suggested that under most circumstances, psychotherapy namely CBT-I had a favorable profile, but pharmacotherapy with prazosin was effective in managing nightmare severity. The sole avail of CBT-I was recommended to improving sleep quality while CBT-I and CBT-I plus IRT showed excellent management of PTSD symptom severity. Exposure to CBT-I isrecommended for depression. The relevant clinical guidelines for the management of individuals with PTSD and sleep disorders may regard this as a reference. PROSPERO: CRD42023415240.

Humoral immunity and safety of respiratory virus vaccines in systemic lupus erythematosus population: a meta-analysis based on twenty-five observational studies.

BACKGROUND: Systemic lupus erythematosus (SLE), an extensive autoimmune disorder, compromises viral resistance and alters immune responses post respiratory virus vaccines. This study aims to assess immune response levels and safety in SLE patients following respiratory virus vaccines. METHODS: Extensive searches, until 1 March 2024, were conducted using PubMed, EMBASE, and Cochrane Library. Outcomes, encompassing seroconversion rate (SCR), antibody and IgG titers, neutralizing antibodies, anti-spike antibodies, anti-receptor binding domain (RBD) IgG, and adverse events, were appraised. RESULTS: Sixteen articles, comprising 25 observational studies, were included. SLE patients exhibited lower SCR (OR = 0.42, 95%CI: 0.26 to 0.69), antibody titers (SMD=-2.84, 95%CI: -3.36 to -1.61), and neutralizing antibodies (OR = 0.27, 95%CI: 0.13 to 0.56) compared to the healthy population post respiratory virus vaccines. Notably, differences were statistically insignificant for anti-RBD IgG (OR = 1.75, 95%CI: 0.10 to 29.42), IgG titers (SMD=-2.54, 95%CI: -5.57 to -0.49), anti-spike antibodies (OR = 0.35, 95%CI: 0.08 to 1.53), injection site discomfort (OR = 1.03, 95%CI: 0.52 to 2.06), fatigue (OR = 1.23, 95%CI: 0.74 to 2.03), fever (OR = 1.02, 95%CI: 0.64 to 1.63), localized reactions (OR = 0.69, 95%CI: 0.37 to 1.30), systemic reactions (OR = 1.00, 95%CI: 0.59 to 1.69), allergic reactions (OR = 5.11, 95%CI: 0.24 to 107.10), self-reported vaccination-related adverse events (OR = 1.61, 95%CI: 0.56 to 4.63), and disease flares after vaccination (OR = 1.00, 95%CI: 0.14 to 7.28). CONCLUSION: Despite the reduced immune response and host protection in SLE patients post-Corona Virus Disease 2019 (COVID-19) and influenza vaccines compared to the healthy population, safety profiles are comparable. Therefore, it is recommended that SLE patients receive COVID-19 and influenza viral vaccines to fortify their resistance.

An RCT META analysis based on the effect of tai chi exercise therapy on the outcome of elderly patients with moderate-to-severe sleep disorders-A systematic review study.

Background: According to statistics, about one-fifth of the world's elderly people suffer from sleep disorders, and the problem of sleep disorders in the elderly is extremely serious, and this problem is one of the important causes of chronic diseases such as hypertension, hyperlipidemia, diabetes mellitus, and coronary heart disease in the elderly. The positive effect of Tai Chi exercise therapy on sleep problems has been confirmed, but at present, the effect of the specific duration of Tai Chi exercise on the improvement of elderly people with moderate to severe sleep disorders varies. Objective: META analysis was used to investigate and find that long-term Tai Chi exercise therapy has the best effect on improving sleep in elderly patients with moderate to severe sleep disorders. Methods: META analysis was performed using Revman 5.3 after searching Web of science, Pubmed, Scopus, The Cochroae Library, OVID, CBM, CNKI, VIP, and other databases, and then filtering and extracting. Results: A total of seven papers were included. Meta-analysis showed that tai chi exercise was more effective in improving sleep problems in elderly patients with sleep disorders compared to the control group, and the difference was significant. This was demonstrated by a decrease in the global Pittsburgh Sleep Quality Index (PSQI) score [SMD = -0.66, 95 % CI (-0.91, -0.41), P < 0.00001], as well as its subdomains of subjective sleep quality [SMD = -0.79, 95 % CI (-1.06, -0.52), P < 0.00001], sleep latency [SMD = -0.80, 95 % CI (-1.21, -0.40), P < 0.00001], sleep duration [SMD = -0.38, 95 % CI (-0.72, -0.04), P = 0.03], habitual sleep efficiency [SMD = -0.58, 95 % CI (-0.84, -0.31), P < 0.0001], sleep disturbance [SMD = -0.51, 95 % CI (-0.78, -0.25), P = 0.00001] and daytime dysfunction [SMD = -0.33, 95 % CI (-0.59, -0.07), P = 0.01]. Improvement was also observed in the Epworth Sleepiness Scale (ESS) and Insomnia Severity Index Scale (ISI). The results showed that the optimal duration and frequency of Tai Chi exercise therapy for improving moderately severe elderly patients with sleep disorders was long-term. Conclusion: This study systematically assessed the efficacy of Tai Chi exercise therapy for elderly patients with moderate-to-severe sleep disorders. Through a meta-analysis of relevant randomized controlled trials (RCTs), it aims to determine the effectiveness of Tai Chi exercise in improving sleep quality in elderly patients with moderate-to-severe sleep disorders, as well as to compare its effects with those of traditional treatments; to analyze the safety of Tai Chi exercise for this patient population and assess its feasibility as a non-pharmacological therapy; and to fill the research gaps and provide more comprehensive and systematic evidence support. This study provides a practical approach to reducing the risk of medication side effects in older adults with sleep disorders and offers a potentially effective non-pharmacological treatment option, especially for those who are unable or unwilling to use medication. Tai chi exercise may not only improve sleep, but also improve coordination, muscle strength, balance, and reduce stress and anxiety in older adults. It also helps older adults socialize and enhances their social connections and emotional support. This study suggests that community centers or activity centers for the elderly can organize tai chi classes to promote the participation of older adults, and can be used as a scientific exercise rehabilitation tool in clinical treatment, incorporating tai chi practice into daily life, such as tai chi practice at a fixed time every day or every week, which not only helps to improve the sleep disorders of older adults, but also improves their overall quality of life.

[Effects of parecoxib sodium analgesia on serum concentrations of neuron-specific enolase and S-100ß and postoperative cognitive function of elderly patients undergoing acute replacement of femoral head].

OBJECTIVE: To explore the effects of parecoxib sodium analgesia on serum concentrations of neuron-specific enolase (NSE) and S-100ß and postoperative cognitive function of elderly patients undergoing acute replacement of femoral head. METHODS: After the approval of institutional review board and the provision of informed consent, 80 patients over 70 years old, undergoing acute replacement of femoral head under combined spinal and epidural anesthesia and midazolam sedation at Qingdao Municipal Hospital and Qingdao Hiser Medical Center from January 2011 to May 2012, were randomly assigned into control group (group C, n = 40) and parecoxib group (group P, n = 40). In group P, parecoxib sodium 20/40 mg (based on weight 50 kg) was administered via an intravenous injection after admission with 12 hours intervals for six times. In group C, morphine 2/4 mg was given initially. Additional morphine 2 mg was given to maintain the pain visual analog scale (VAS) of 3 points or less in both groups. Primary observation indices: (1) postoperative time and additional amount of morphine; (2) rate of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) at 3 days, 1 week, 3 months and 6 months postoperation (T1-T4); (3) se rum levels of NSE and S-100ß were measured at the timepoints of before analgesia (t0), before anesthesia (t1), end of surgery (t2) and 6 hours, 24 hours, 48 hours postoperation (t3-t5); (4) other serious complications. RESULTS: Compared with group C, the additional amount of morphine, postoperative time, rate of POD and POCD at T1-T4, the level of NSE at t2-t5 and S-100ß at t1-t5 were lower in group P (P < 0.05). No other serious complications were observed. CONCLUSIONS: Parecoxib sodium analgesia reduces the rate of POD and POCD in elderly patients with neuroprotective effects.

Preparation of polyhydroxyalkanoate-based magnetic microspheres for carbonyl reductase purification and immobilization.

A polyhydroxyalkanoate (PHA) magnetic microsphere was designed for one-step purification and immobilization of a novel carbonyl reductase (RLSR5) from recombinant Escherichia coli lysate. The hydrophobic core of this microsphere was composed of a highly biocompatible polymer, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx), in which magnetic Fe3O4 particles were embedded during solvent evaporation. The hydrophilic shell of the fusion protein formed by PHA particle-binding protein (PhaP) and RLSR5 (PR) was expressed in recombinant E. coli. The magnetic core of Fe3O4@PHBHHx directly purified the hydrophilic shell from the E. coli lysate, and the two self-assembled to form Fe3O4@PHBHHx-PR through hydrophobic and hydrophilic interactions, eliminating the separation of the fusion protein. The microstructure, magnetic properties, morphology, size, and dispersion of Fe3O4@PHBHHx-PR were investigated by XRD, VSM, SEM, TEM, elemental mapping and DLS. It was found that Fe3O4@PHBHHx-PR correctly assembled, with a well dispersed spherical structure at the nanoscale and superparamagnetism properties. The amount of RLSR5 immobilized on PHA microspheres reached 121.9 mg/g. The Fe3O4@PHBHHx-PR was employed to synthesize (R)-tolvaptan with 99 % enantiomeric excess and 97 % bioconversion efficiency, and the catalyst maintained 78.6 % activity after 10 recovery cycles. These PHA magnetic microspheres are versatile carriers for enzyme immobilization and demonstrate improved stability and reusability of the free enzyme.

Characterization and Application of a Novel Glucose Dehydrogenase with Excellent Organic Solvent Tolerance for Cofactor Regeneration in Carbonyl Reduction.

An efficient cofactor regeneration system has been developed to provide a hydride source for the preparation of optically pure alcohols by carbonyl reductase-catalyzed asymmetric reduction. This system employed a novel glucose dehydrogenase (BcGDH90) from Bacillus cereus HBL-AI. The gene encoding BcGDH90 was found through the genome-wide functional annotation. Homology-built model study revealed that BcGDH90 was a homo-tetramer, and each subunit was composed of ßD-αE-αF-αG-ßG motif, which was responsible for substrate binding and tetramer formation. The gene of BcGDH90 was cloned and expressed in Escherichia coli. The recombinant BcGDH90 exhibited maximum activity of 45.3 U/mg at pH 9.0 and 40 °C. BcGDH90 showed high stability in a wide pH range of 4.0-10.0 and was stable after the incubation at 55 °C for 5 h. BcGDH90 was not a metal ion-dependent enzyme, but Zn2+ could seriously inhibit its activity. BcGDH90 displayed excellent tolerance to 90% of acetone, methanol, ethanol, n-propanol, and isopropanol. Furthermore, BcGDH90 was applied to regenerate NADPH for the asymmetric biosynthesis of (S)-(+)-1-phenyl-1,2-ethanediol ((S)-PED) from hydroxyacetophenone (2-HAP) with high concentration, which increased the final efficiency by 59.4%. These results suggest that BcGDH90 is potentially useful for coenzyme regeneration in the biological reduction.

Successful Treatment of pMMR MSS IVB Colorectal Cancer Using Anti-VEGF and Anti-PD-1 Therapy in Combination of Gut Microbiota Transplantation: A Case Report.

Immune checkpoint inhibitors (ICI) have shown great promise in treating advanced or metastatic colorectal cancer (mCRC), especially for CRC patients with deficient mismatch repair (dMMR) and high microsatellite instability (MSI-H). For the remainder of CRC patients presenting with proficient mismatch repair (pMMR) and microsatellite stable (MSS) or low microsatellite instability (MSI-L), ICI showed a low-level response. This study describes a 57-year-old Chinese man diagnosed with pMMR MSS IVb CRC with liver metastasis. Primarily, the patient was administered two consecutive treatments, one composed of an anti-EGFR and modified FOLFOX6 and the other composed of an anti-VEGF and FOLFOXIRI. Due to severe chemotherapy side effects, the patient discontinued treatment and decided to take a third investigational treatment, where an anti-PD-1 and an anti-VEGF were given in combination with fecal microbiota transplantation (FMT) capsules. The patient achieved a partial response (PR), and the tumor size decreased to the extent amenable to surgical resection. After surgery, the patient achieved a pathological complete response (pCR). Patients with pMMR MSS or MSI-L hardly benefit from anti-PD-1 immunotherapy. This study indicated that, to a limited extent, FMT might improve the response to ICI for pMMR MSS CRC patients.

Clinical outcomes of recommended active pharmacotherapy agents from NICE guideline for post-traumatic stress disorder: Network meta-analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a mental disorder that can emerge after an individual experiences a traumatic event such as physical abuse, sexual/relationship violence, combat exposure, witnessing death, or serious injury. This study aimed to identify the most suitable drugs for the management of PTSD based on a network meta-analysis (NMA). METHODS: Six databases (Ovid Medline, EMBase, CENTRAL, PsycINFO, Ovid Health and Psychosocial Instruments, and Web of Science) were searched from inception to September 6, 2022. RESULTS: Thirty articles with a total of 5170 participants were included. Compared with placebo, active drugs including olanzapine (SMD = -0.66, 95% CI: -1.19 to -0.13), risperidone (SMD = -0.23, 95% CI: -0.42 to -0.03), quetiapine (SMD = -0.49, 95% CI: -0.93 to -0.04), venlafaxine (SMD = -0.29, 95% CI: -0.42 to -0.16), sertraline (SMD = -0.23, 95% CI: -0.34 to -0.11), paroxetine (SMD = -0.48, 95% CI: -0.60 to -0.36) and fluoxetine (SMD = -0.27, 95% CI: -0.42 to -0.12), significantly reduced the total clinician-administered PTSD scale score. CONCLUSION: The results of this study support the use of paroxetine, venlafaxine, and quetiapine as first-line treatment for PTSD. In addition, quetiapine is recommended for patients with PTSD affected by symptoms of hyperarousal and re-experience disorder. Clinicians should prescribe medications based on the severity of PTSD symptoms and other conditions to develop the best treatment strategy for this patient population.