AnnoPRO: a strategy for protein function annotation based on multi-scale protein representation and a hybrid deep learning of dual-path encoding.

Protein function annotation has been one of the longstanding issues in biological sciences, and various computational methods have been developed. However, the existing methods suffer from a serious long-tail problem, with a large number of GO families containing few annotated proteins. Herein, an innovative strategy named AnnoPRO was therefore constructed by enabling sequence-based multi-scale protein representation, dual-path protein encoding using pre-training, and function annotation by long short-term memory-based decoding. A variety of case studies based on different benchmarks were conducted, which confirmed the superior performance of AnnoPRO among available methods. Source code and models have been made freely available at: https://github.com/idrblab/AnnoPRO and https://zenodo.org/records/10012272.

MoDAFold: a strategy for predicting the structure of missense mutant protein based on AlphaFold2 and molecular dynamics.

Protein structure prediction is a longstanding issue crucial for identifying new drug targets and providing a mechanistic understanding of protein functions. To enhance the progress in this field, a spectrum of computational methodologies has been cultivated. AlphaFold2 has exhibited exceptional precision in predicting wild-type protein structures, with performance exceeding that of other methods. However, predicting the structures of missense mutant proteins using AlphaFold2 remains challenging due to the intricate and substantial structural alterations caused by minor sequence variations in the mutant proteins. Molecular dynamics (MD) has been validated for precisely capturing changes in amino acid interactions attributed to protein mutations. Therefore, for the first time, a strategy entitled 'MoDAFold' was proposed to improve the accuracy and reliability of missense mutant protein structure prediction by combining AlphaFold2 with MD. Multiple case studies have confirmed the superior performance of MoDAFold compared to other methods, particularly AlphaFold2.

Intraoperative electroencephalogram features related to frailty in older patients: an exploratory prospective observational study.

Frailty is an independent risk factor for the increased incidence of postoperative delirium (POD). To date, the effect of frailty on intraoperative electroencephalogram (EEG) changes remains unexplored. The present study, an exploratory analysis of a prospective cohort study, aimed to investigate the differences in EEG characteristics between frail and robust patients. This prospective observational study was conducted between December 2020 and November 2021. The preoperative frailty status was assessed using the FRAIL scale. The patients' baseline (before anesthesia) and intraoperative EEG data were collected using a brain function monitor. Finally, 20 robust and 26 frail older patients scheduled for elective spinal surgery or transurethral prostatectomy under propofol-based general anesthesia were included in the final analysis. Baseline and intraoperative EEG spectrogram and power spectra were compared between the frail and robust groups. No differences were observed in baseline EEG between the frail and robust groups. When the intraoperative EEG spectral parameters were compared, the alpha peak frequency (10.56 ± 0.49 vs. 10.14 ± 0.36 Hz, P = 0.002) and alpha peak, delta, theta, alpha, and beta powers were lower in the frail group. After adjusting for age, Charlson Comorbidity Index (CCI), and mini-mental state examination (MMSE) score, the FRAIL score was still negatively associated with total, delta, theta, alpha, and beta powers. Frail patients had reduced EEG (0-30 Hz) power after the induction of propofol-based general anesthesia. After adjusting for age, CCI, and MMSE score, frail patients still showed evidence of reduced δ, θ, α, and ß power.

EEG-derived pain threshold index-guided versus standard care during propofol-remifentanil anesthesia: A randomized controlled trial.

Purpose: The pain threshold index (PTI), a novel index of nociception based on spontaneous EEG wavelet analysis, has been reported to provide reliable accuracy for predicting postoperative pain and hemodynamic reactivity. The present study is aimed to investigate whether PTI-guided analgesia reduces the pain intensity and rate of remedial analgesia in the post-anesthesia care unit (PACU). Methods: A total of 122 females undergoing elective gynecologic surgeries had been randomized to receive either PTI-guided analgesia (PTI group) or standard clinical care (control group). Remifentanil administration in the PTI group was guided by PTI to maintain the value between 40 and 65, while that in the control group was guided by hemodynamic changes. The primary outcome was remedial analgesia rate in the PACU. The postoperative pain scores, intraoperative remifentanil requirements, opioid-related adverse events and perioperative serum stress hormone concentrations between the two groups were also compared. Findings: It was found that 23 of 58 patients (40%) in the control group and 8 of 58 patients (14%) in the PTI group needed remedial analgesia. The relative risk of receiving remedial analgesia was 2.88 (95% CI, 1.40-5.89, P = 0.002) in the control group. Sufentanil consumption in the PACU (µg) was lower in the PTI group (P = 0.002) than in the control group. Remifentanil and propofol consumption, opioid-related adverse events between these two groups were comparable. Implications: PTI-guided analgesia during gynaecologic operations resulted in 25.87% less remedial analgesia. However, studies with different PTI thresholds and larger, more diverse populations should be conducted to further demonstrate the clinical effectiveness of PTI.

Multi-phase composite synchronization of three vibrators in a space far-resonant vibration system.

To improve the problem that self-synchronization and control synchronization of vibration systems are respectively restricted by their inherent characteristics and product cost, by combining them a multi-phase composite synchronization scheme is proposed for space far-resonant vibration system actuated by three vibrators. Based on the established mathematical model and sliding mode control (SMC) algorithm, controller of one vibrator is designed to implement the multi-phase control synchronization. Then self-synchronization mechanism of the other two vibrators is analyzed through small parameter average method and Routh-Hurwitz criterion. Besides, necessary calculation and simulation cases in multi-phase composite synchronization state are further conducted. Research results indicate that the multi-phase composite synchronization of three vibrators can be carried out in stable operation regions, but chaotic behaviors, since severe mass asymmetry of the eccentric rotors (ERs), will be induced when the phase differences (PDs) between two coaxial vibrators are controlled in -1.99∼-1.67 and 1.63∼2.1 (rad), and the controlled PDs around -0.4 (rad) should be avoid to ensure a stronger synchronization ability.

Contribution of intraoperative electroencephalogram suppression to frailty-associated postoperative delirium: mediation analysis of a prospective surgical cohort.

BACKGROUND: Frailty is a risk factor for postoperative delirium (POD), and has led to preoperative interventions that have reduced, but not eliminated, the risk. We hypothesised that EEG suppression, another risk factor for POD, mediates some of the frailty risk for POD. METHODS: A prospective cohort study enrolled patients aged 65 yr or older, scheduled for noncardiac surgery under total intravenous anaesthesia. Frailty was assessed using the FRAIL scale. Cumulative duration of EEG suppression, defined as an amplitude between -5 and 5 µV for >0.5 s during anaesthesia, was measured. POD was diagnosed by either confusion assessment method (CAM), CAM-ICU, or medical records. The severity of POD was assessed using the Delirium Rating Scale - Revised-98 (DRS). Mediation analysis was used to estimate the relationships between frailty, EEG suppression, and severity of POD. RESULTS: Among 252 enrolled patients, 51 were robust, 129 were prefrail, and 72 were frail. Patients classified as frail had higher duration of EEG suppression than either the robust (19 vs 0.57 s, P<0.001) or prefrail groups (19 vs 3.22 s, P<0.001). Peak delirium score was higher in the frail group than either the robust (17 vs 15, P<0.001) or prefrail groups (17 vs 16, P=0.007). EEG suppression time mediated 24.2% of the frailty-DRS scores association. CONCLUSION: EEG suppression time mediated a statistically significant portion of the frailty-POD association in older noncardiac surgery patients. Trials directed at reducing EEG suppression time could result in intraoperative interventions to reduce POD in frail patients. CLINICAL TRIAL REGISTRATION: ChiCTR2000041092 (Chinese Clinical Trial Registry).

Analysis of iodine nutrition status of children aged 8 - 10 and pregnant women in Fushun City, Liaoning Province in 2021 / 中华地方病学杂志

Objective:To study the iodine nutrition status of children aged 8 to 10 and pregnant women and thyroid of children in Fushun City, Liaoning Province, and to provide data for formulation of prevention and control programs on iodine deficiency disorders in Fushun.Methods:In 2021, according to population probability proportional sampling method (PPS), 1 street (township) was selected from 7 districts and counties (Dongzhou District, Wanghua District, Dongzhou District, Xinfu District, Fushun County, Xinbin County and Qingyuan County) in Fushun City according to 5 directions (east, south, west, north and middle) and 1 primary school was selected from each street (township). Forty to 50 children aged 8 to 10 from each primary school and 20 pregnant women were selected from each street (township). Urine samples and salt samples of children and pregnant women were collected for urine iodine and salt iodine levels detection, and thyroid gland of children was examined to calculate the goiter rate. Urine iodine was determined by "Determination of Iodine in Urine Part 1: Method for Determination of Iodine in Urine by As 3+-Ce 4+ Eatalytic Spectrophotometry", salt iodine was determined by "General Test Method in Salt Industry - Determination of Iodine", and children's thyroid was examined by Doppler B-ultrasound. Children iodine nutrition criteria: urinary iodine median < 100 μg/L was iodine deficiency; 100 - < 200 μg/L was suitable for iodine; 200 - < 300 μg/L was more than the appropriate amount of iodine; ≥300 μg/L was iodine excess. Pregnant women iodine nutrition criteria: urinary iodine median < 150 μg/L was iodine deficiency; 150 - < 250 μg/L was suitable for iodine. 250 - < 500 μg/L was more than the appropriate amount of iodine; ≥500 μg/L was iodine excess. Criteria for iodized salt: 18 - 33 mg/kg was qualified iodized salt; < 5 mg/kg was non-iodized salt; 5 - < 18 or > 33 mg/kg was unqualified iodized salt. Results:A total of 1 647 children aged 8 to 10 years were selected, including 829 males and 818 females. The median urinary iodine of children was 203.4 μg/L. The median urinary iodine of children by district and county ranged from 151.6 to 232.4 μg/L, and the difference was statistically significant ( H = 24.227, P < 0.001). A total of 700 urine samples were collected from pregnant women. The median urine iodine was 164.7 μg/L. The median urine iodine of pregnant women by district and county ranged from 131.3 to 193.0 μg/L, and the difference was statistically significant ( H = 48.516, P < 0.001). A total of 2 347 salt samples were collected, including 2 329 iodized salt samples, with iodized salt coverage rate of 99.23% (2 329/2 347). There were 2 254 qualified iodized salt samples, and the rate of qualified iodized salt was 96.04% (2 254/2 347). There was no correlation between total urinary iodine level and salt iodine content ( r = 0.129, P > 0.05). The thyroid gland of 1 439 children was examined, and 25 children of them had goiter, with an enlargement rate of 1.74% (25/1 439), lower than the national standard for elimination of iodine deficiency disorders (< 5%), and the difference between counties and districts was statistically significant (χ 2 = 31.692, P < 0.01). Conclusion:The iodine nutrition of 8 to 10 years old children and pregnant women in Fushun City, Liaoning Province in 2021 is basically at an appropriate level, the rate of qualified iodized salt is high, and the goiter rate of children conforms to the national elimination standards of iodine deficiency disorders.

Application value of ERCP in the diagnosis and treatment of pancreaticobiliary maljunction in children / 中华胰腺病杂志

Objective:To investigate the application value of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and treatment of pancreaticobiliary maljunction (PBM) in children.Methods:The clinical data of 77 PBM children who underwent ERCP in General Surgery Department of Children's Hospital affiliated to Nanjing Medical University between January 2018 and December 2021 were retrospectively evaluated. Clinical characteristics, classification and post-operative nursing interventions were summarized, and vital signs, changes of biochemical markers and the occurrence of postoperative complications were compared and recorded.Results:77 patients were classified according to Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM), including 34 patients with type A, 18 patients with type B, 21 patients with type C, and 4 patients with type D. There were 68 patients with congenital bile duct dilation and 9 patients without congenital bile duct dialtion. 92 ERCP procedures were performed under general anesthesia, and 91 cases were successful with a success rate of 98.91%. Among these cases, including 7 cases of endoscopic sphincterotomy, 28 cases of endoscopic balloon dilation of the nipple, 22 cases of endoscopic probe dilation, 22 cases of endoscopic stone removal by balloon or basket, 35 cases of endoscopic retrograde biliary stent drainage, 4 cases of endoscopic pancreatic duct drainage, 18 cases of endoscopic nasobiliary drainage, 2 cases of endoscopic nasobiliary drainage, and 14 cases of biliary stent removal. In 77 children with PBM, body temperature, FLACC score, and laboratory-related biochemical indexes including direct bilirubin, serum amylase, ALT, AST and CGT decreased significantly after ERCP, and all the differences were statistically significant (all P value <0.001). The incidence of postoperative complications was 15.38%(14/91), including hyperamylasemia in 9 cases (9.89%) and abdominal pain in 5 cases (5.49%). Conclusions:ERCP is safe and effective in the treatment of abnormal confluence of pancreatic duct in children.

Effectiveness of massage therapy on anxiety and depression of COVID-19 convalescent: A protocol for systematic review and meta-analysis.

BACKGROUND: Novel coronavirus pneumonia was first detected in Wuhan, China, in late December 2019. Its widespread infectivity and strong pathogenicity has posed a great threat to public health, seriously affecting social production and life. The disease caused by this virus has been officially named COVID-19 (coronavirus disease 2019) by the World Health Organization (WHO). Tuina (massage) therapy is 1 of the widely employed complementary and alternative medicine interventions in the world. As a useful therapy implemented on human's skin, muscles and joints, tuina (massage) has unique advantages in the field of medicine. This systematic review and meta-analysis will summarize the current evidence of tuina (massage) used as an intervention for COVID-19. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness and safety of massage therapy in treating all patients recovering from COVID-19: Wanfang and Pubmed Database, china national knowledge infrastructure database, cochrane central register of controlled trials, cumulative index of nursing and allied health literature and excerpta medica database. Each database will be searched from inception to October 2022. The entire process will include study selection, data extraction, risk of bias assessment and meta-analyses. RESULTS: This proposed study will evaluate the effectiveness and safety of massage therapy for patients recovering from COVID-19. CONCLUSIONS: This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for patients recovering from COVID-19.

Integrated constructed wetland and bioelectrochemistry system approach for simultaneous enhancment of p-chloronitrobenzene and nitrogen transformations performance.

Constructed wetlands (CWs) integrated with the bioelectrochemical system (BES-CW) to stimulate bio-refractory compounds removal holds particular promise, owing to its inherent greater scale and well-recognized environmentally benign wastewater advanced purification technology. However, the knowledge regarding the feasibility and removal mechanisms, particularly the potential negative effects of biorefractory compounds on nitrogen removal performance for the CWs is far insufficient. This study performed a critical assessment by using BES-CW (ECW) and conventional CW (CW) to investigate the effects of p-Chloronitrobenzene (pCNB) on nitrogen transformations in CWs. The results showed that low concentration (1 mg·L-1) of pCNB would inhibit the ammonia oxidation in CWs, while ECW could improve its tolerance to pCNB to a certain level (8 mg·L-1) due to the high pCNB degradation efficiencies (2.5 times higher than CWs), accordingly, much higher TN and nitrate removal efficiencies were observed in ECWs, 81.71% - 96.82% (TN) higher than CWs, further leading to a lower N2O emission from ECWs than CWs. The main intermediate of pCNB degradation was p-Chloroaniline (pCAN) and the genera Geobacter and Propionimicrobium were consider to be the responsible pCNB degradation bacteria in the present study. However, too high concentration (20 mg·L-1) of pCNB would have a huge impact on ECW and CW, especially microbial biomass. Nevertheless, ECW could improve the 1.87 times higher microbial biomass than CW on the substrate. Accordingly, considerably higher functional gene abundance was observed in ECW. Therefore, the introduction of BES has great potential to ensure CW stability when treating industrial wastewater containing bio-refractory compounds.

Strategies for Proteome-Wide Quantification of Glycosylation Macro- and Micro-Heterogeneity.

Protein glycosylation governs key physiological and pathological processes in human cells. Aberrant glycosylation is thus closely associated with disease progression. Mass spectrometry (MS)-based glycoproteomics has emerged as an indispensable tool for investigating glycosylation changes in biological samples with high sensitivity. Following rapid improvements in methodologies for reliable intact glycopeptide identification, site-specific quantification of glycopeptide macro- and micro-heterogeneity at the proteome scale has become an urgent need for exploring glycosylation regulations. Here, we summarize recent advances in N- and O-linked glycoproteomic quantification strategies and discuss their limitations. We further describe a strategy to propagate MS data for multilayered glycopeptide quantification, enabling a more comprehensive examination of global and site-specific glycosylation changes. Altogether, we show how quantitative glycoproteomics methods explore glycosylation regulation in human diseases and promote the discovery of biomarkers and therapeutic targets.

The association between perioperative pupillary parameters and postoperative acute pain: A pilot cross-sectional study.

OBJECTIVE: We aim to explore the capacity of perioperative pupillary variables to predict acute pain in the post-anesthesia care unit (PACU). METHODS: Patients scheduled to undergo thoracic or abdominal surgery under general anesthesia between April 2021 and June 2021 were enrolled. We measured the pupil diameter, pupillary light reflex (PLR), and pupillary reflex dilatation 5 min before anesthesia induction (T1), 5 min after intubation (T2), at the end of anesthesia (T3), immediately before extubation (T4), and 5 min after extubation (T5). We assessed the early postoperative pain intensity in the PACU using Numeric Rating Scales (NRS) at recovery, 5 min after recovery, and 10 min after recovery. Logistic regression models were used to evaluate the association between perioperative pupillary variables and postoperative pain intensity. RESULTS: Fifty-one patients were enrolled, 50 of whom were included in the final analysis. A total of 13 patients (26%) needed remedial analgesia in the PACU. Pupil parameters at T1, T2, T3, and T5 were not associated with NRS in the PACU. Multiple logistic regression models and receiver operating characteristic (ROC) curves indicated that only latency of PLR at T4 can predict postoperative acute pain. The ROC analysis showed that the cutoff value for latency of PLR at T4 was 0.29 s to discriminate between no pain and pain, and the area under the curve was 0.778 (95% CI 0.634-0.922, p = 0.002) with sensitivity 50.0% and specificity 91.7%. CONCLUSION: The latency of PLR immediately before extubation may be a useful predictor for postoperative acute pain in the PACU.

Ablation of ORMDL3 impairs adipose tissue thermogenesis and insulin sensitivity by increasing ceramide generation.

OBJECTIVE: Genome-wide association studies identified ORMDL3 as an obesity-related gene, and its expression was negatively correlated with body mass index. However, the precise biological roles of ORMDL3 in obesity and lipid metabolism remain uncharacterized. Here, we investigate the function of ORMDL3 in adipose tissue thermogenesis and high fat diet (HFD)-induced insulin resistance. METHODS: Ormdl3-deficient (Ormdl3-/-) mice were employed to delineate the function of ORMDL3 in brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. Glucose and lipid homeostasis in Ormdl3-/- mice fed a HFD were assessed. The lipid composition in adipose tissue was evaluated by mass spectrometry. Primary adipocytes in culture were used to determine the mechanism by which ORMDL3 regulates white adipose browning. RESULTS: BAT thermogenesis and WAT browning were significantly impaired in Ormdl3-/- mice upon cold exposure or administration with the ß3 adrenergic agonist. In addition, compared to WT mice, Ormdl3-/- mice displayed increased weight gain and insulin resistance in response to HFD. The induction of uncoupling protein 1 (UCP1), a marker of thermogenesis, was attenuated in primary adipocytes derived from Ormdl3-/- mice. Importantly, ceramide levels were elevated in the adipose tissue of Ormdl3-/- mice. In addition, the reduction in thermogenesis and increase in body weight caused by Ormdl3 deficiency could be rescued by inhibiting the production of ceramides. CONCLUSION: Our findings suggest that ORMDL3 contributes to the regulation of BAT thermogenesis, WAT browning, and insulin resistance.

Effect of moxibustion on quality of life in tumor patients: network Meta-analysis / 中国针灸

OBJECTIVE@#To rank the effectiveness of various moxibustion methods on the quality of life in tumor patients, and explore the best treatment plan of moxibustion for improving the quality of life in tumor patients from the perspective of evidence-based medicine.@*METHODS@#The Chinese and English literature of randomized controlled trial (RCT) of the effect of moxibustion on the quality of life in tumor patients were searched in PubMed, EMbase, Cochrane Library, CNKI, SinoMed, Wanfang and VIP. The retrieval time was from the establishment of the databases to October 31, 2020. The R3.6.2 and Stata15.0 software were used for network Meta-analysis based on Bayesian model.@*RESULTS@#A total of 30 Chinese RCTs were included, including 2 169 patients, involving 16 interventions. In terms of the effectiveness of improving quality of life, the top three treatments were special moxibustion plus other therapies 1 (either of tendon acupuncture, acupoint pressing, acupoint injection, etc.), wheat-grain moxibustion and mild moxibustion. The special moxibustion methods were the combination of fire-dragon moxibustion, thunder-fire moxibustion, fuyang fire moxibustion and moxa salt-bag moxibustion. The number of literature of these four moxibustion methods was small. Considering the clinical application of moxibustion, it was concluded that wheat-grain moxibustion ranked first.@*CONCLUSION@#The adjuvant treatment of wheat-grain moxibustion is more effective than other moxibustion methods on improving the quality of life in tumor patients, but the results needed to be further verified because the bias risk of RCT included in this study is high and the sample size is small.

Exploration of the continuing education of physicians in a primary military hospital: competency-based neurological education / 中华医学教育探索杂志

During the mandate duty in primary military hospital, we conducted continuing neurological education combining with the hospitals trait and department needs. By using the concept of competency-based education, we have explored a pattern of continuing medical education suitable for primary physicians. Thematic approach was implemented for acquiring professional knowledge, formative evaluation was applied for training effect assessment, and scientific clinical thinking was emphasized for promoting the demand of lifelong learning. Under the communication and efforts of teachers and learners, we have obtained good clinical effect and positive social affection by the competency-based neurological education.

Quantitative Analysis of the Cardiac Phosphoproteome in Response to Acute ß-Adrenergic Receptor Stimulation In Vivo.

ß-adrenergic receptor (ß-AR) stimulation represents a major mechanism of modulating cardiac output. In spite of its fundamental importance, its molecular basis on the level of cell signalling has not been characterised in detail yet. We employed mass spectrometry-based proteome and phosphoproteome analysis using SuperSILAC (spike-in stable isotope labelling by amino acids in cell culture) standardization to generate a comprehensive map of acute phosphoproteome changes in mice upon administration of isoprenaline (ISO), a synthetic ß-AR agonist that targets both ß1-AR and ß2-AR subtypes. Our data describe 8597 quantitated phosphopeptides corresponding to 10,164 known and novel phospho-events from 2975 proteins. In total, 197 of these phospho-events showed significantly altered phosphorylation, indicating an intricate signalling network activated in response to ß-AR stimulation. In addition, we unexpectedly detected significant cardiac expression and ISO-induced fragmentation of junctophilin-1, a junctophilin isoform hitherto only thought to be expressed in skeletal muscle. Data are available via ProteomeXchange with identifier PXD025569.

Effect of Intraoperative Dexmedetomidine on Recovery of Gastrointestinal Function After Abdominal Surgery in Older Adults: A Randomized Clinical Trial.

Importance: Postoperative ileus is common after abdominal surgery, and small clinical studies have reported that intraoperative administration of dexmedetomidine may be associated with improvements in postoperative gastrointestinal function. However, findings have been inconsistent and study samples have been small. Further examination of the effects of intraoperative dexmedetomidine on postoperative gastrointestinal function is needed. Objective: To evaluate the effects of intraoperative intravenous dexmedetomidine vs placebo on postoperative gastrointestinal function among older patients undergoing abdominal surgery. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at the First Affiliated Hospital of Anhui Medical University in Hefei, China (lead site), and 12 other tertiary hospitals in Anhui Province, China. A total of 808 participants aged 60 years or older who were scheduled to receive abdominal surgery with an expected surgical duration of 1 to 6 hours were enrolled. The study was conducted from August 21, 2018, to December 9, 2019. Interventions: Dexmedetomidine infusion (a loading dose of 0.5 µg/kg over 15 minutes followed by a maintenance dose of 0.2 µg/kg per hour) or placebo infusion (normal saline) during surgery. Main Outcomes and Measures: The primary outcome was time to first flatus. Secondary outcomes were postoperative gastrointestinal function measured by the I-FEED (intake, feeling nauseated, emesis, physical examination, and duration of symptoms) scoring system, time to first feces, time to first oral feeding, incidence of delirium, pain scores, sleep quality, postoperative nausea and vomiting, hospital costs, and hospital length of stay. Results: Among 808 patients enrolled, 404 were randomized to receive intraoperative dexmedetomidine, and 404 were randomized to receive placebo. In total, 133 patients (60 in the dexmedetomidine group and 73 in the placebo group) were excluded because of protocol deviations, and 675 patients (344 in the dexmedetomidine group and 331 in the placebo group; mean [SD] age, 70.2 [6.1] years; 445 men [65.9%]) were included in the per-protocol analysis. The dexmedetomidine group had a significantly shorter time to first flatus (median, 65 hours [IQR, 48-78 hours] vs 78 hours [62-93 hours], respectively; P < .001), time to first feces (median, 85 hours [IQR, 68-115 hours] vs 98 hours [IQR, 74-121 hours]; P = .001), and hospital length of stay (median, 13 days [IQR, 10-17 days] vs 15 days [IQR, 11-18 days]; P = .005) than the control group. Postoperative gastrointestinal function (as measured by the I-FEED score) and delirium incidence were similar in the dexmedetomidine and control groups (eg, 248 patients [72.1%] vs 254 patients [76.7%], respectively, had I-FEED scores indicating normal postoperative gastrointestinal function; 18 patients [5.2%] vs 12 patients [3.6%] had delirium on postoperative day 3). Conclusions and Relevance: In this randomized clinical trial, the administration of intraoperative dexmedetomidine reduced the time to first flatus, time to first feces, and length of stay after abdominal surgery. These results suggest that this therapy may be a viable strategy to enhance postoperative recovery of gastrointestinal function among older adults. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800017232.

Evaluation and Optimization of High-Field Asymmetric Waveform Ion-Mobility Spectrometry for Multiplexed Quantitative Site-Specific N-Glycoproteomics.

The heterogeneity and complexity of glycosylation hinder the depth of site-specific glycoproteomics analysis. High-field asymmetric-waveform ion-mobility spectrometry (FAIMS) has been shown to improve the scope of bottom-up proteomics. The benefits of FAIMS for quantitative N-glycoproteomics have not been investigated yet. In this work, we optimized FAIMS settings for N-glycopeptide identification, with or without the tandem mass tag (TMT) label. The optimized FAIMS approach significantly increased the identification of site-specific N-glycopeptides derived from the purified immunoglobulin M (IgM) protein or human lymphoma cells. We explored in detail the changes in FAIMS mobility caused by N-glycopeptides with different characteristics, including TMT labeling, charge state, glycan type, peptide sequence, glycan size, and precursor m/z. Importantly, FAIMS also improved multiplexed N-glycopeptide quantification, both with the standard MS2 acquisition method and with our recently developed Glyco-SPS-MS3 method. The combination of FAIMS and Glyco-SPS-MS3 methods provided the highest quantitative accuracy and precision. Our results demonstrate the advantages of FAIMS for improved mass spectrometry-based qualitative and quantitative N-glycoproteomics.

Black liquor increases methane production from excess pulp and paper industry sludge.

The aim of the study was to use black liquor produced during the soda pulping process in a pulp and paper mill to increase methane production during pulp and paper industry sludge treatment and decrease the treatment cost. The effects of black liquor on sludge solubilization and methane production were assessed and the economic feasibility of the process was evaluated. Black liquor and NaOH were found to be equivalent in the thermochemical pretreatment process to solubilize sludge and disintegrate flocs. However, adding black liquor increased the background chemical oxygen demand and volatile fatty acid concentration and increased the amount of methane produced by approximately 7-30%. A start-up delay was emphasized by first-order kinetics model due to black liquor addition while methane production remained stable. Economic assessments of five scenarios were performed. It was found to be economically feasible to use black liquor to replace NaOH for the thermal pretreatment process. The surplus methane generated suggested that co-digestion of sludge and black liquor allows surplus bioenergy to be produced during the thermochemical pretreatment anaerobic digestion process.

High-throughput functional screening for next-generation cancer immunotherapy using droplet-based microfluidics.

Currently, high-throughput approaches are lacking in the isolation of antibodies with functional readouts beyond simple binding. This situation has impeded the next generation of cancer immunotherapeutics, such as bispecific T cell engager (BiTE) antibodies or agonist antibodies against costimulatory receptors, from reaching their full potential. Here, we developed a highly efficient droplet-based microfluidic platform combining a lentivirus transduction system that enables functional screening of millions of antibodies to identify potential hits with desired functionalities. To showcase the capacity of this system, functional antibodies for CD40 agonism with low frequency (<0.02%) were identified with two rounds of screening. Furthermore, the versatility of the system was demonstrated by combining an anti-Her2 × anti-CD3 BiTE antibody library with functional screening, which enabled efficient identification of active anti-Her2 × anti-CD3 BiTE antibodies. The platform could revolutionize next-generation cancer immunotherapy drug development and advance medical research.