Search

Objective: Liver cancer is a major health concern globally and in China. This analysis investigated deaths and disability-adjusted life years (DALYs) with respect to etiologies and risk factors for liver cancer in China and worldwide. Methods: Global and China-specific data were collected on liver cancer deaths, DALYs, and age-standardized rates (ASRs) from the Global Burden of Disease Study 2019 database. Liver cancer etiologies were classified into five groups and risk factors were categorized into three levels. Each proportion of liver cancer burden was calculated in different geographic regions. The joinpoint regression model were used to assess the trends from 1990–2019. Results: Liver cancer accounted for 484,577 deaths worldwide in 2019 with an ASR of 5.9 per 100,000 population. China had an elevated liver cancer death ASR in 2019 and males had an ASR 1.7 times the global rate. The global ASR for DALYs peaked at 75–79 years of age but peaked earlier in China. Hepatitis B virus was the prominent etiology globally (39.5%) and in China (62.5%), followed by hepatitis C virus and alcohol consumption. In high sociodemographic index countries, non-alcoholic steatohepatitis has gained an increasing contribution as an etiologic factor. The liver cancer burden due to various etiologies has decreased globally in both genders. However, metabolic risk factors, particularly obesity, have had a growing contribution to the liver cancer burden, especially among males. Conclusions: Despite an overall decreasing trend in the liver cancer burden in China and worldwide, there has been a rising contribution from metabolic risk factors, highlighting the importance of implementing targeted prevention and control strategies that address regional and gender disparities.

Objective: The burden of gastric cancer (GC) across different age groups needs updating. We determined the GC global, regional, and national burden profiles and changes in incidence for 3 sequential 5-year intervals from 2003 to 2017. Methods: The latest incidence and mortality estimates of GC from 185 countries and regions were extracted from the GLOBOCAN 2022 database. The 5-year interval age-standardised incidence rates (ASIRs) were evaluated using cancer registry data from volumes X–XII of the Cancer Incidence in Five Continents (CI5). Correlation analysis was used to evaluate the relationship between ASIR or the age-standardised mortality rate (ASMR) and the Human Development Index (HDI). Results: There was an estimated global 968,000 new GC cases and 660,000 deaths in 2022, with male predominance. GC ASIRs and ASMRs were 9.2 and 6.1 per 100,000 persons, respectively. East Asia had the highest burden, with 53.8% of cases and 48.2% of deaths among all geographic regions. There was a significant correlation between ASIR and HDI. Over three 5-year intervals from 2003 to 2017, the incidence of GC notably decreased in most countries but peaked at 2008–2012 in New Zealand, Turkey, and South Africa. Several countries in Europe, Oceania, and America suggest an increasingly concerning trend among younger individuals, especially females. Conclusions: GC is a significant health issue, especially among males and in geographic regions with an HDI, such as eastern Asia. While the incidence of GC is decreasing in many countries due to prevention efforts and improved treatments, a rising trend persists among younger individuals. Comprehensive prevention strategies tailored to different age patterns are clearly needed.

Objective: This study aimed to provide a comprehensive overview of the global burden of esophageal cancer (EC) and determine the temporal trends and factors influencing changes in the global burden. Methods: The latest incidence and mortality data for EC worldwide were obtained from GLOBALCAN 2022. The mortality and disability-adjusted life years (DALYs) rates for EC from 1990–2019 were sourced from the 2019 Global Burden of Diseases. Trends in EC mortality and DALYs attributable to 11 risk factors or clusters of risk were analyzed using the joinpoint regression model. The trends in age-related EC burden were assessed using a decomposition approach. Results: An estimated 511,054 new cases of EC were diagnosed in 2022 with 445,391 deaths worldwide. Approximately 75% of cases and deaths occurred in Asia. Nearly 50% of global EC deaths and DALYs were attributed to tobacco use in men in 2019, while 20% were attributed to high body mass index (BMI) in women. From 1990–2019, EC deaths and DALYs attributable to almost all risk factors had declining trends, while EC deaths and DALYs attributed to high BMI in men had upward trends. The age-related EC burden exhibited an upward trend driven by population growth and aging, which contributed to 307.4 thousand deaths and 7.2 million DALYs due to EC. Conclusions: The EC burden remains substantial worldwide. Effective tobacco and obesity control measures are critical for addressing the risk-attributable burden of EC. Population growth and aging pose challenges for EC prevention and control efforts.

IntroductionPlant growth-promoting rhizobacteria (PGPR) and elevated CO2 (eCO2) have demonstrated their individual potential to enhance plant yield and quality through close interaction with rhizosphere microorganisms and plant growth. However, the efficacy of PGPR under eCO2 on rhizosphere microbiome and, ultimately, plant yield and active ingredient accumulation are not yet fully understood.MethodsThis study investigated how the medicinal plant Pseudostellaria heterophylla (P. heterophylla) and its rhizosphere microbes respond to PGPR (Bacillus subtilis and Pseudomonas fluorescens) at eCO2 (1,000 ppm).Results and DiscussionIt was found that the yield and active ingredient polysaccharides accumulation in the tuber of P. heterophylla were significantly increased by 38 and 253%, respectively. This promotion has been associated with increased root development and changes in the indigenous microbial community. Metagenomics analysis revealed a significant reduction in pathogenic Fusarium abundance in the rhizosphere. Potential biocontrol bacteria Actinobacteria and Proteobacteria were enriched, especially the genera Bradyrhizobium and Rhodanobacter. The reshaping of the rhizosphere microbiome was accompanied by the upregulation of biological pathways related to metabolite biosynthesis in the rhizosphere. These modifications were related to the promotion of the growth and productivity of P. heterophylla. Our findings highlighted the significant role played by PGPR in medicinal plant yield and active ingredient accumulation when exposed to eCO2.

Dynamic Vehicle Routing Problem with Time Windows (DVRPTW) is an extension of the traditional VRPTW by considering dynamic customer characteristics. In this problem, new customers with specific time windows are received dynamically as time progresses and must be incorporated into the evolving schedule. The goal of DVRPTW is to use the minimum number of vehicles to fulfill all the customer demands with the minimum total traveling time. Little work has been done for solving this dynamic variant. In this paper, an evolutionary algorithm using Ant Colony System and Kuhn-Munkres bipartite graph matching, named ACS-KM, is proposed. It can tackle the dynamic issues during the evolutionary process. Experiments show that the proposed algorithm is very effective and has fast convergence. It achieves the best results on 40 out of 48 benchmark instances. For the DVRPTW instances with different levels of dynamicity, the algorithm can always produce better solutions than the previous works.

Abstract Chronic pain is often associated with cognitive decline, which could influence the quality of the patient’s life. Recent studies have suggested that Toll-like receptor 3 (TLR3) is crucial for memory and learning. Nonetheless, the contribution of TLR3 to the pathogenesis of cognitive decline after chronic pain remains unclear. The level of TLR3 in hippocampal neurons increased in the chronic constriction injury (CCI) group than in the sham group in this study. Importantly, compared to the wild-type (WT) mice, TLR3 knockout (KO) mice and TLR3-specific neuronal knockdown mice both displayed improved cognitive function, reduced levels of inflammatory cytokines and neuronal apoptosis and attenuated injury to hippocampal neuroplasticity. Notably, extracellular RNAs (exRNAs), specifically double-stranded RNAs (dsRNAs), were increased in the sciatic nerve, serum, and hippocampus after CCI. The co-localization of dsRNA with TLR3 was also increased in hippocampal neurons. And the administration of poly (I:C), a dsRNA analog, elevated the levels of dsRNAs and TLR3 in the hippocampus, exacerbating hippocampus-dependent memory. In additon, the dsRNA/TLR3 inhibitor improved cognitive function after CCI. Together, our findings suggested that exRNAs, particularly dsRNAs, that were present in the condition of chronic neuropathic pain, activated TLR3, initiated downstream inflammatory and apoptotic signaling, caused damage to synaptic plasticity, and contributed to the etiology of cognitive impairment after chronic neuropathic pain.

Objective Little is known about the correlation between perioperative concentrations of inflammatory biomarkers and postoperative complications. This study explored whether the plasma concentrations and perioperative changes of procalcitonin (PCT), C reactive protein (CRP) and high-sensitivity CRP (hsCRP) could predict the risk of postoperative morbidity in elderly patients undergoing elective non-cardiac surgery.Design A nested case–control study.Setting A tertiary hospital in China.Participants A total of 498 patients aged ≥65 years from a prospective cohort who underwent elective non-cardiac surgery between June 2020 and April 2021.Primary outcome measures The primary outcomes were the efficacy of plasma concentrations of PCT, CRP and hsCRP in predicting the risk of Clavien-Dindo Classification (CDC) ≥grade 3 and major complications. The major complications included mortality, an intensive care unit stay length >24 hour, cardiovascular events, acute kidney injury, postoperative cognitive dysfunction and infections.Results For major complications, the area under the curve (AUC) (95% CI) of PCT-24 hours, PCT change and PCT change rate were 0.750 (0.698 to 0.803), 0.740 (0.686 to 0.795) and 0.711 (0.651 to 0.771), respectively. The AUC (95% CI) of CRP-24 hours, CRP change, CRP change rate and hsCRP baseline were 0.835 (0.789 to 0.881), 0.818 (0.770 to 0.867), 0.691 (0.625 to 0.756) and 0.616 (0.554 to 0.678), respectively. For complications ≥CDC grade 3, the AUC (95% CI) of PCT-24 hours, PCT change and PCT change rate were 0.662 (0.543 to 0.780), 0.643 (0.514 to 0.772) and 0.627 (0.494 to 0.761), respectively. The AUC (95% CI) of CRP-24 hours and hsCRP baseline were 0.649 (0.527 to 0.771) and 0.639 (0.530 to 0.748), respectively.Conclusions PCT-24 hours, CRP-24 hours, the change of perioperative PCT and CRP were valuable predictors of major complications occurring within 30 days after non-cardiac surgery in the elderly.Trial registration number China Clinical Trial Registry: ChiCTR1900026223.

The post-translational modifications (PTMs) of proteins play a crucial role in increasing the functional diversity of proteins and are associated with the pathogenesis of various diseases. This review focuses on a less explored PTM called citrullination, which involves the conversion of arginine to citrulline. This process is catalyzed by peptidyl arginine deiminases (PADs). Different members of the PAD family have distinct tissue distribution patterns and functions. Citrullination is a post-translational modification of native proteins that can alter their structure and convert them into autoantigens; thus, it mediates the occurrence of autoimmune diseases. CD4+ T cells, including Th1, Th2, and Th17 cells, are important immune cells involved in mediating autoimmune diseases, allergic reactions, and tumor immunity. PADs can induce citrullination in CD4+ T cells, suggesting a role for citrullination in CD4+ T cell subset differentiation and function. Understanding the role of citrullination in CD4+ T cells may provide insights into immune-related diseases and inflammatory processes.

Summary: Background: Endoscopy surveillance is recommended for mild-moderate dysplasia and negative endoscopy findings every 3 years and 5 years, respectively, but evidence is limited. This study aimed to assess long-term esophageal cancer (EC) incidence and mortality after a single endoscopy screening. Methods: We included individuals at high risk of EC aged 40–69 years who underwent endoscopy screening in 2007–2012 at six centres in rural China and had a baseline diagnosis of negative endoscopy findings, mild dysplasia, or moderate dysplasia. Participants were followed up for EC incidence and mortality. Cumulative incidence and mortality rates of EC were estimated by Kaplan–Meier analyses. Cox regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between baseline endoscopy diagnosis and the risk of EC incidence and mortality. EC incidence and mortality after a single endoscopy screening were compared with those of the population in rural China by the standardized incidence ratio (SIR) and standardized mortality ratio (SMR). Findings: A total of 42,827 participants (40,977 with negative endoscopy findings, 1562 with mild dysplasia, and 288 with moderate dysplasia) were included; 268 EC cases and 128 EC deaths were identified during a median follow-up of 10.62 years. The cumulative EC incidence at 10 years was 0.45% (0.38–0.52) in the group with negative endoscopy findings, 2.39% (1.62–3.16) in the mild dysplasia group, and 8.90% (5.57–12.24) in the moderate dysplasia group, and the cumulative EC mortality at 10 years was 0.23% (0.18–0.27), 0.96% (0.46–1.46), and 2.50% (0.67–4.33), respectively. Compared with individuals with negative endoscopy findings, the HRs for EC incidence and mortality in the mild dysplasia group were 3.52 (2.49–4.97) and 2.43 (1.41–4.19), and those in the moderate dysplasia group were 13.18 (8.78–19.76) and 6.46 (3.13–13.29), respectively. The SIR was 0.53 (0.40–0.70) for the group with negative endoscopy findings, 1.95 (1.69–2.24) for the mild dysplasia group, and 6.75 (6.25–7.28) for the moderate dysplasia group, with the SMRs of 0.43 (0.31–0.58), 1.07 (0.88–1.29) and 2.67 (2.36–3.01), respectively. Interpretation: Individuals with negative endoscopy findings after a single endoscopy screening had a lower EC risk than the general population for up to 10.62 years, while those with mild-moderate dysplasia had an elevated risk. Our results support endoscopy surveillance for mild-moderate dysplasia every 3 years and suggest extending the interval to 10 years after a negative endoscopy finding. Funding: National Key R&D Programme of China, Special Project of Beijing-Tianjin-Hebei Basic Research Cooperation, and Sanming Project of Medicine in Shenzhen.

An analysis of the J/ψ→ηη′γ decay by the BESIII collaboration claims the observation of an exotic state η1(1855) with IGJPC=0+1−+. To establish its C-parity partner η1′(1855) in the picture of the KK¯1(1400) molecular state, we propose that J/ψ→η1′(1855)η(′) receives the main contributions from the final state interaction of KK⁎(K+K⁎−, K−K⁎+, K0K¯⁎0, and K¯0K⁎0). Specifically, K and K⁎ in J/ψ→KK⁎ decays transform as η1′(1855)η(′), by exchanging a K1(1400). We predict B(J/ψ→η1′(1855)η)=(6.3−3.5+12.6)×10−6, and B(J/ψ→η1′(1855)η′)=(6.5−4.6+6.6)×10−6, which can be studied in the J/ψ→K⁎K¯⁎η(′) decays.

BackgroundPopulation-based esophageal cancer (EC) screening trials and programs have been conducted in China for decades; however, screening strategies have been adopted in different regions and screening profiles are unclear. ObjectiveWe performed a meta-analysis to profile EC screening in China by positivity rate, compliance rate, and endoscopy findings, aiming to provide explicit evidence and recommendations for EC screening programs. MethodsEnglish (PubMed, Embase) and Chinese (China National Knowledge Infrastructure, Wanfang) language databases were systematically searched for population-based EC screening studies in the Chinese population until December 31, 2022. A meta-analysis was performed by standard methodology using a random-effects model. Pooled prevalence rates were calculated for three groups: high-risk areas with a universal endoscopy strategy, rural China with a risk-stratified endoscopic screening (RSES) strategy, and urban China with an RSES strategy. Positive cases included lesions of severe dysplasia, carcinoma in situ, intramucosal carcinoma, submucosal carcinoma, and invasive carcinoma. ResultsThe pooled positivity rate of the high-risk population was higher in rural China (44.12%) than in urban China (23.11%). The compliance rate of endoscopic examinations was the highest in rural China (52.40%), followed by high-risk areas (50.11%), and was the lowest in urban China (23.67%). The pooled detection rate of positive cases decreased from 1.03% (95% CI 0.82%-1.30%) in high-risk areas to 0.48% (95% CI 0.25%-0.93%) in rural China and 0.12% (95% CI 0.07%-0.21%) in urban China. The pooled detection rate of low-grade intraepithelial neoplasia (LGIN) was also in the same order, being the highest in high-risk areas (3.99%, 95% CI 2.78%-5.69%), followed by rural China (2.55%, 95% CI 1.03%-6.19%) and urban China (0.34%, 95% CI 0.14%-0.81%). Higher detection rates of positive cases and LGIN were observed among males than among females and at older ages. The pooled early detection rate was 81.90% (95% CI 75.58%-86.88%), which was similar to the rates in high-risk areas (82.09%), in rural China (80.76%), and in urban China (80.08%). ConclusionsUnder the current screening framework, a higher screening benefit was observed in high-risk areas than in other regions. To promote EC screening and reduce the current inequality of screening in China, more focus should be given to optimizing strategies of high-risk individual assessment and surveillance management to improve compliance with endoscopic examination. Trial RegistrationPROSPERO CRD42022375720; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=375720

Sanghuangporus, a medicinal mushroom, has gained significant attention due to its beneficial properties. Phenolic acids are among the major bioactive compounds in Sanghuangporus, known for their antioxidant and anti-inflammatory activities. To precisely quantify the phenolic acid content, we developed a method utilizing ultra-high-performance liquid chromatography with triple quadrupole (UHPLC-QqQ). This study optimized the UHPLC-QqQ conditions to simultaneously separate and detect eight phenolic acids in Sanghuangporus baumii (Pilát) L.W. Zhou and Y.C. Dai, including chlorogenic acid, p-coumaric acid, caffeic acid, cryptochlorogenic acid, protocatechuic acid, ferulic acid, sinapic acid, and syringic acid. The separation process utilized a ZORBAX Eclipse Plus C18 column using 0.01% formic acid and 2 mmol/L ammonium formate in water as the aqueous phase and methanol containing 0.01% formic acid and 2 mmol/L ammonium formate as the organic phase. Calibration curves were constructed using standard solutions to quantitatively determine the phenolic acid content. The results showed significant variation in phenolic acid content among S. baumii fruiting bodies, with Protocatechuic acid, p-coumaric acid, and caffeic acid being the most abundant. This method is valuable for quantifying phenolic acid compounds under different cultivation conditions. It provides excellent sensitivity, selectivity, and reproducibility for the quantification of phenolic acids in Sanghuangporus, contributing to a better understanding of its chemical composition and potential health benefits. This approach represents a novel technical means for the simultaneous analysis of compound phenolic acids in Sanghuangporus fruiting bodies.

WUSCHEL (WUS) is a crucial transcription factor in regulating plant stem cell development, and its expression can also improve genetic transformation. However, the ectopic expression of WUS always causes pleiotropic effects during genetic transformation, making it important to understand the regulatory mechanisms underlying these phenomena. In our study, we found that the transient expression of the maize WUS ortholog ZmWus2 caused severe leaf necrosis in Nicotiana benthamiana. We performed transcriptomic and non-target metabolomic analyses on tobacco leaves during healthy to wilted states after ZmWus2 transient overexpression. Transcriptomic analysis revealed that ZmWus2 transformation caused active metabolism of inositol trisphosphate and glycerol-3-phosphate, while also upregulating plant hormone signaling and downregulating photosystem and protein folding pathways. Metabolomic analysis mainly identified changes in the synthesis of phenylpropanoid compounds and various lipid classes, including steroid synthesis. In addition, transcription factors such as ethylene-responsive factors (ERFs), the basic helix–loop–helix (bHLH) factors, and MYBs were found to be regulated by ZmWus2. By integrating these findings, we developed a WUS regulatory model that includes plant hormone accumulation, stress responses, lipid remodeling, and leaf necrosis. Our study sheds light on the mechanisms underlying WUS ectopic expression causing leaf necrosis and may inform the development of future genetic transformation strategies.

A rapid, precise, and dependable method for quantifying flavonoids in the fruiting bodies of Sanghuangporus was established using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS). Separation was achieved using a ZORBAX Eclipse Plus C18 column (1.8 μm, 3.0 mm × 100 mm) with a 15 min gradient of a mobile phase consisting of 0.01% aqueous formic acid and 2 mm/L ammonium formate (mobile phase A), and 0.01% formic acid and 2 mm/L ammonium formate in methanol (mobile phase B). A mass spectrometry analysis was performed using the multiple reaction monitoring (MRM) mode with an electrospray ion source. This method enabled the simultaneous detection of 10 flavonoids (sakuranetin, quercitrin, myricitrin, kaempferol, luteolin, rutin, hyperoside, kaempferol-3-O-rutinoside, catechin, and catechin gallate) in the fruiting bodies of Sanghuangporus. Additionally, we applied this method to analyze the flavonoid content in fruiting bodies of various Sanghuangporus species. The results revealed substantial variations in flavonoid content, up to a 100-fold difference, among different species, with myricitrin, hyperoside, and rutin identified as the most abundant flavonoids. This protocol serves as a valuable tool for quantifying flavonoid compounds in different Sanghuangporus species or under diverse cultivation conditions, particularly for identifying species with high levels of specific flavonoid compounds.

Abstract Background Due to the complexity and high heterogeneity of the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the guidelines (global initiative for chronic obstructive, GOLD) is unable to fully guide the treatment of AECOPD. Objectives To provide a rapid treatment in line with the development of the AECOPD after admission. In this paper, we propose a multi-stage feature fusion (MSFF) framework combining machine learning to track the diseases deterioration risk of the AECOPD. Methods First, we identify 408 AECOPD patients as the study population. Then, feature segment and fusion methods are applied to generate the phased data set. Finally, human studies are designed to evaluate the performance of the MSFF framework. Results The experimental results show that the proposed framework is potential to obtain the full-process tracking of deterioration risk for the AECOPD patients. The proposed MSFF framework achieves a higher overall accuracy average and F1 scores than the four physician groups i.e., IM, Surgery, Emergency, and ICU. Conclusions The proposed MSFF model may serve as a useful disease tracking tool to estimate the deterioration risk at each stage, and finally achieve the disease monitoring and management for AECOPD patients.

The application of soil beneficial bacteria (SBB) in agriculture is steadily increasing as it provides a promising way to replace chemical fertilisers and other supplements. Although the role of SBB as a biofertiliser is well understood, little is known about the response of soil physiochemical properties via the change in soil enzymatic activities with SBB growth. In this study, sterilised bulk soil was inoculated with Bacillus subtilis (BS) and Pseudomonas fluorescens (PF), which exhibit excellent characteristics in vitro for potentially improving soil quality. It is found that the contents of bioavailable nitrogen and ammonium in soil inoculated with SBB increased significantly, up to 34% and 57% relative to a control. This resulted from the enhancement of soil urease activity with BS and PF treatments by approximately 90% and 70%, respectively. The increased soil urease activity can be explained by the increased microorganism activity evident from the larger population size of BS (0.78–0.97 CFU mL−1/CFU mL−1) than PF (0.55–0.79 CFU mL−1/CFU mL−1) (p < 0.05). Results of principal component analysis also reinforce the interaction apparent in the significant relationship between soil urease activity and microbial biomass carbon (p < 0.05). Therefore, it can be concluded that the enhancement of soil enzymatic activities induced bulk soil fertility upregulation because of bacterial growth. These results demonstrate the application of SBB to be a promising strategy for bulk soil amendment, particularly nutrient restoration.

BackgroundMalignant hyperthermia (MH) is a rare life-threatening anesthetic emergency. With respect to the high fatality rate, difficulty in early recognition, and the lack of disease-specific drug (ie, dantrolene) in China, more effort is needed to strengthen early diagnosis and effective treatment of MH emergencies. Nowadays, mobile health (mHealth) apps are changing the way of medical practice; they can serve as an accessible tool to help anesthesiologists deal with MH crises. However, no related mHealth-based emergency system is available currently. ObjectiveThe aim of this study is to outline the protocol for the development of a WeChat applet used to design a National Remote Emergency System for Malignant Hyperthermia (MH-NRES) in China, as well as the protocol for the evaluation of the user experience and perception of the system. MethodsThe system adopts the client-server architecture, with a custom user interface operating as clients and the back-end system operating as the server. The client-side software was developed using uni-app technology with Vue.js-based framework, which consists of 6 modules: Quick Diagnosis, Dantrolene Mobilization, Instruction on Dantrolene Use, MH Treatment, Recovery Period Treatment, and DNA Test and Biopsy. The back-end system was developed based on the Spring framework. The system will be evaluated by administrating a modified user version of the Mobile App Rating Scale. Pilot testing will be conducted in Sichuan Province, China, and a subsequent evaluation on a national scale is planned. ResultsThe theoretical framework design of this system was completed in August 2021. The development of the system was completed in February 2022, and the refinement is currently ongoing. Pilot testing after the implementation of the system in Sichuan Province is planned to take 2 months, and the subsequent evaluation on a national scale is planned to take 2 months. ConclusionsWe have described a novel approach using the WeChat applet to develop the MH-NRES. Findings from the usability testing process in the current study may lead to refinements and is expected to suggest that this system is both feasible and welcomed by anesthesiologists. Depending on the availability of research funding, this system will be extended nationally across China. International Registered Report Identifier (IRRID)PRR1-10.2196/37084

Abstract Background Ophiocordyceps sinensis is an important traditional Chinese medicine for its comprehensive active ingredients, such as cordycepin, cordycepic acid, and Cordyceps polysaccharide. O. sinensis zjut, a special strain isolated from O. sinensis, has similar pharmacological functions to wild O. sinensis. Currently, O. sinensis with artificial cultivation has been widely studied, but systematic fundamental research at protein levels has not been determined. Results Proteomes of O. sinensis zjut at different culture periods (growth period, 3rd day; pre-stable period, 6th day; and stable period, 9th day) were relatively quantified by relative isotope markers and absolute quantitative technology. In total, 4005 proteins were obtained and further annotated with Gene Ontology, Kyoto Encyclopedia of Genes and Genomes database. Based on the result of the annotations, metabolic pathways of active ingredients, amino acids and fatty acid were constructed, and the related enzymes were exhibited. Subsequently, comparative proteomics of O. sinensis zjut identified the differentially expressed proteins (DEPs) by growth in different culture periods, to find the important proteins involved in metabolic pathways of active ingredients. 605 DEPs between 6d-VS-3d, 1188 DEPs between 9d-VS-3d, and 428 DEPs between 9d-VS-6d were obtained, respectively. Conclusion This work provided scientific basis to study protein profile and comparison of protein expression levels of O. sinensis zjut, and it will be helpful for metabolic engineering works to active ingredients for exploration, application and improvement of this fungus.

Background/purpose Vaginal delivery, compared with Cesarean delivery, remains a less chosen mode of delivery for twin pregnancy. We studied the maternal and perinatal outcomes of twin pregnancy with different modes of delivery. Methods A retrospective study with data collected from a regional hospital, including vital twin pregnancies delivered at gestational age of 32 weeks and above. Medical charts were reviewed for prenatal conditions and postpartum outcomes. Results Ninety-eight pairs of twins were included and 44.9% were delivered via vaginal delivery. Women in the vaginal delivery group were significantly younger (32.5 ±4.3 years versus 34.8 ±4.6 years, p < 0.01), multiparous (34.1% versus 18.5%) and with more twins in vertex-vertex presentation (70.5% versus 33.3%) compared with women in the Cesarean delivery group. There were no differences between maternal postpartum complications and neonatal outcomes in both groups. The outcomes showed longer inter-twin delivery time interval (5.7 ± 5.6 versus 1.5 ± 0.9 min, p < 0.01), less estimated blood loss (198.7 ± 144.1 versus 763.2 ± 332.3 mL, p < 0.01), and shorter maternal hospital stay (3.0 ± 0.5 versus 5.7 ± 0.5 days, p< 0.01) in the vaginal delivery group. Twenty newborns had Apgar score below seven at birth. Logistic regression analysis revealed that low Apgar score was independently related to younger maternal age, maternal obstetric diseases and fetal non-vertex presentation. Gestational weeks and mode of delivery were not related to low Apgar score. Conclusion With careful case selection, vaginal delivery could be safely performed in twin pregnancies with less estimated blood loss and better recovery than Cesarean delivery.

Abstract Ophiocordyceps sinensis has been used as a traditional medicine or healthy food in China for thousands of years. Hirsutella sinensis was reported as the only correct anamorph of O. sinensis. It is reported that the laboratory-grown H. sinensis mycelium has similar clinical efficacy and less associated toxicity compared to the wild O. sinensis. The research of the H. sinensis is becoming more and more important and urgent. To gain deeper insight into the biological and pharmacological mechanisms, we sequenced the genome of H. sinensis. The genome of H. sinensis (102.72 Mb) was obtained for the first time, with > 99% coverage. 10,200 protein-encoding genes were predicted based on the genome sequence. A detailed secondary metabolism analysis and structure verification of the main ingredients were performed, and the biosynthesis pathways of seven ingredients (mannitol, cordycepin, purine nucleotides, pyrimidine nucleotides, unsaturated fatty acid, cordyceps polysaccharide and sphingolipid) were predicted and drawn. Furthermore, infection process and mechanism of H. sinensis were studied and elaborated in this article. The enzymes involved in the infection mechanism were also predicted, cloned and expressed to verify the mechanism. The genes and proteins were predicted and annotated based on the genome sequence. The pathways of several active components in H. sinensis were predicted and key enzymes were confirmed. The work presented here would improve the understanding of the genetic basis of this organism, and contribute to further research, production and application of H. sinensis.

Abstract Supercritical CO2 (SCCO2) is considered as a promising alternative heat extraction fluid in the enhanced geothermal system (EGS) which can reduce atmospheric CO2 emissions and water waste. However, the heat extraction performance of SCCO2 is greatly affected by its thermophysical properties, which are high sensitivity to temperature/pressure. In this study, by considering the impacts of temperature and pressure on thermophysical properties of SCCO2, a thermo‐hydro‐mechanical coupling numerical model was established to investigate the effects of the initial reservoir temperature as well as the SCCO2 injection pressure and temperature on heat extraction. The variations of reservoir permeability and mass productivity as well as the net heat extraction rate (HER) were simulated by implementing the model into COMSOL Multiphysics, which showed a good consistency compared with the high‐temperature/pressure triaxial seepage experiments. Simulation results indicate that there are three distinct stages in mass productivity including the slow decline stage, the rapid increase stage, and the stabilization stage. Increasing the initial reservoir temperature or the injection temperature will reduce the net HER to varying degrees. Appropriate increase of the injection pressure and injection temperature can extend Stage 2 duration which can subsequently enhance the mass productivity and the net HER. Meanwhile, the higher injection pressure or the lower injection temperature will inhibit heat compensation within rock masses and accelerate the reservoir heat depletion. This study provides guidance for optimizing the injection parameters of CO2‐EGS and aims to enhance the net HER while ensuring a reasonable reservoir production life.

Abstract Hollow grouted rock bolts are widely used in deep soft rock roadways. The density of grout has a significant influence on the anchorage quality. However, there is still a lack of effective methods to detect the grouting quality fast, accurately, and extensively. Based on the wave velocity and the law of stress wave transmission and reflection in the impedance mismatch, non-destructive experiment focused on the defect in the anchorage was conducted. The wavelet transform was used to analyze the test signals. The test results show that the free length of hollow grouted rock bolt could be accurately detected through the analysis of the stress wave signal by using the low-pass filter in the wavelet toolbox. The grouted length, defect length, and specific position of the anchorage section can be accurately detected through the analysis of the stress wave signal by using the high-pass filter in the wavelet toolbox. The research can provide experiment foundation for further study of grouting quality based on the non-destructive methods.

It is of great significance for the sustainable development of global energy to develop hot dry rock (HDR) geothermal resources by using enhanced geothermal system (EGS) technology. Different working fluids in EGS have different heat recovery efficiencies. Therefore, this paper takes water and CO2 as the heat-carrying media and establishes a thermal hydraulic mechanical coupling model to simulate the heat recovery process in high-temperature rock mass. By considering the different confining pressures, rock temperature, and injection pressure, the advantages of H2O-EGS and CO2-EGS are obtained. The results show that with the increase of confining pressure, the heat recovery efficiency of water is significantly higher than that of CO2, but at higher reservoir temperature, CO2 has more advantages as a heat-carrying medium. The net heat extraction rate will increase with the increase of injection pressure, which indicates that the mass flow rate plays a leading role in the heat recovery process and increases the injection pressure of fluid which is more conducive to the thermal recovery of EGS. This study will provide a technical guidance for thermal energy exploitation of hot dry rock under different geological conditions.

By taking advantage of the pH-sensitive drug release property of graphene oxide (GO) after intracellular uptake, we prepared folic acid (FA)-conjugated GO (GOFA) for targeted delivery of the chemotherapeutic drug doxorubicin (DOX). GOFA-DOX was further encapsulated in an injectable in-situ forming thermo-sensitive hyaluronic acid-chitosan-g-poly(N-isopropylacrylamide) (HACPN) hydrogel for intratumoral delivery of DOX. As the degradation time of HACPN could be extended up to 3 weeks, intratumoral delivery of GOFA-DOX/HACPN could provide controlled and targeted delivery of DOX through slow degradation HACPN and subsequent cellular uptake of released GOFA-DOX by tumor cells through interactions of GOFA with folate receptors on the tumor cell’s surface. GOFA nano-carrier and HACPN hydrogel were first characterized for the physico-chemical properties. The drug loading experiments indicated the best preparation condition of GOFA-DOX was by reacting 0.1 mg GOFA with 2 mg DOX. GOFA-DOX showed pH-responsive drug release with ~5 times more DOX released at pH 5.5 than at pH 7.4 while only limited DOX was released from GOFA-DOX/HACPN at pH 7.4. Intracellular uptake of GOFA by endocytosis and release of DOX from GOFA-DOX in vitro could be confirmed from transmission electron microscopic and confocal laser scanning microscopic analysis with MCF-7 breast cancer cells. The targeting effect of FA was revealed when intracellular uptake of GOFA was blocked by excess FA. This resulted in enhanced in vitro cytotoxicity as revealed from the lower half maximal inhibitory concentration (IC50) value of GOFA-DOX (7.3 μg/mL) compared with that of DOX (32.5 μg/mL) and GO-DOX (10 μg/mL). The flow cytometry analysis indicated higher apoptosis rates for cells treated with GOFA-DOX (30%) compared with DOX (8%) and GO-DOX (11%). Animal studies were carried out with subcutaneously implanted MCF-7 cells in BALB/c nude mice and subject to intratumoral administration of drugs. The relative tumor volumes of control (saline) and GOFA-DOX/HACPN groups at day 21 were 2.17 and 1.79 times that at day 0 with no significant difference. In comparison, the relative tumor volumes of treatment groups at the same time were significantly different at 1.02, 0.67 and 0.48 times for DOX, GOFA-DOX and GOFA-DOX/HACPN groups, respectively. The anti-tumor efficacy was also supported by images from an in vivo imaging system (IVIS) using MCF-7 cells transfected with luciferase (MCF-7/Luc). Furthermore, tissue biopsy examination and blood analysis indicated that intratumoral delivery of DOX using GOFA-DOX/HACPN did not elicit acute toxicity. Taken together, GOFA-DOX/HACPN could be deemed as a safe and efficient intratumoral drug delivery system for breast cancer therapy.

OBJECTIVE: Increasing evidence suggests that, when used in combination, tumor necrosis factor-α (TNF-α) synergizes with traditional chemotherapeutic drugs to exert a heightened antitumor effect. The present study investigated the antitumor efficacy of recombinant mutated human TNF-α specifically targeted to the tumor vasculature (RGD-rmhTNF-α) combined with the chemotherapeutic agent doxorubicin in 2 murine allografted tumor models. METHODS: Mice bearing hepatoma or sarcoma allografted tumors were treated with various doses of RGD-rmhTNF-α alone or in combination with doxorubicin (2 mg/kg). We then evaluated tumor growth and tumor vessel permeability as well as intratumoral levels of RGD-rmhTNF-α and doxorubicin. RESULTS: RGD-rmhTNF-α treatment enhanced the permeability of the tumor vessels and increased intratumoral doxorubicin levels. In addition, intratumoral RGD-rmhTNF-α levels were significantly higher than that of rmhTNF-α. In both of the tested tumor models, administering RGD-rmhTNF-α in combination with doxorubicin resulted in an enhanced antitumor response compared to either treatment alone. Double-agent combination treatment of doxorubicin with 50,000 IU/kg RGD-rmhTNF-α induced stronger antitumor effects on H22 allografted tumor-bearing mice than the single doxorubicin agent alone. Moreover, doxorubicin with 10,000 IU/kg RGD-rmhTNF-α synergized to inhibit tumor growth in S180 allografted tumor-bearing mice. CONCLUSIONS: These results suggest that targeted delivery of low doses of RGD-rmhTNF-α into the tumor vasculature increases the antitumor efficacy of chemotherapeutic drugs.

This study aims to prepare biphasic osteochondral scaffolds based on seamless joining of sintered polymer and polymer/ceramic microspheres for co-culture of chondrocytes and bone marrow stem cells (BMSCs). Poly(lactide-co-glycolide) (PLGA) microspheres and 10% nanohydroxyapatite (nHAP)-incorporated PLGA (PGA/nHAP) microspheres were prepared through the oil-in-water precipitation method. Virgin (V) and composite (C) scaffolds were prepared from 250–500 µm PLGA and PLGA/nHAP microspheres, respectively, while osteochondral (OC) scaffolds were fabricated through the combination of V and C scaffolds. Physico-chemical properties of scaffolds were characterized through microscopic-spectroscopic evaluations. The effect of nHAP in scaffolds was investigated through thermogravimetric analysis and mechanical testing, while surface hydrophobicity was tested through contact angle measurements. Rabbit chondrocytes and BMSCs were used for cell culture, and cell morphology and proliferation were determined from SEM and DNA assays. Alizarin red and Alcian blue stains were used to identify the in vitro bone and cartilage tissue-specific regeneration, while cetylpyridinium chloride was used to quantitatively estimate calcium in mineralized bone. For co-culture in OC scaffolds, BMSCs were first seeded in the bone part of the scaffold and cultured in osteogenic medium, followed by seeding chondrocytes in the cartilage part, and cultured in chondrocyte medium. High cell viability was confirmed from the Live/Dead assays. Actin cytoskeleton organization obtained by DAPI-phalloidin staining revealed proper organization of chondrocytes and BMSCs in OC scaffolds. Immunofluorescent staining of bone (type I collagen and osteocalcin (OCN)) and cartilage marker proteins (type II collagen (COL II)) confirmed cellular behavior of osteoblasts and chondrocytes in vitro. Using an ectopic osteochondral defect model by subcutaneous implantation of co-cultured OC scaffolds in nude mice confirmed cell proliferation and tissue development from gross view and SEM observation. IF staining of OCN and COL II in the bone and cartilage parts of OC scaffolds and tissue-specific histological analysis exhibited a time-dependent tissue re-modeling and confirmed the potential application of the biphasic scaffold in osteochondral tissue engineering.