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Abstract Background More than 50% of colorectal cancer(CRC) patients experience cancer-related psychological burden after radical surgery, which can seriously affect their physical wellness, quality of life and even survival outcomes. Our research team developed a six-week Traditional Chinese Medicine Combined Online Group Psychotherapy (TCM-eRhab) and proved its efficacy on relieving cancer-related anxiety, depression and fear of cancer recurrence though phase I single arm clinical trial (n = 40). Large sample size randomized controlled clinical trial(RCT) is necessary to further evaluate TCM-eRhab’s role on improving quality of life and survival outcomes among this population. Methods We design a phase II RCT study, in which 210 CRC patients who have received radical surgery (stage I-III) will be recruited. Eligible patients will be randomly assigned to TCM-eRhab group or usual care group by 2:1 ratio. Patients in the intervention group will receive the structured TCM-eRhab program for six weeks, while patients in control group will receive usual care only. The primary outcomes are quality of life, severity of anxiety, depression and fear of cancer recurrence. Cancer recurrence rate will also be calculated according to long term follow-up data. Discussion As one of the first RCTs to evaluate the impacts of TCM combined psychological therapy to improve CRC patients’ quality of life after surgery, the results from this study will provide innovative knowledge and evidence on integrating TCM into CRC survivorship care and mind–body intervention model.

Abstract Background Depression is a prevalent issue among older adults, affecting their quality of life and overall well-being. Exercise is an effective means of relieving depressive symptoms in older adults, but the optimal dose for different exercise types remains unclear. As such, the aim of this meta-analysis was to examine the dose–response relationship between overall and specific types of exercise with depression symptoms in older adults. Methods This systematic review and network meta-analysis included a search of PubMed, Medline, Embase, PsycINFO, Cochrane library, and Web of Science for randomized controlled trials of exercise in older adults with depression symptoms from inception to 15 July 2023. Comprehensive data extraction covered dose, treatment regimen, demographics and study duration. Dosage metrics, encompassing METs-min/week, were scrutinized in correlation with the Minimal Clinically Importance Difference (MCID). Results A total of 47 studies involving 2895 participants and 7 kinds of exercise were included in the review. Without considering the dose, the results of our network meta-analysis indicated that Walking was the most effective in alleviating depression in older adults, in addition to Aerobic exercise (AE), Yoga, Qigong, Resistance training (RT), and Tai Chi (TC), which were equally effective. However, the results of the dose–response analysis found that Aerobic exercise was most effective at a dose of 1000 METs-min/week. It is noteworthy that Walking is significantly effective in alleviating depressive symptoms in older adults at very low doses. In terms of clinical benefits, we found that overall exercise doses in the range of 600 ~ 970 METs-min/week were clinically effective. Considering the specific types of exercise, Aerobic exercise, Resistance training, Walking, and Yoga were found to be effective at doses ranging from 820 ~ 1000 METs-min/week, 520 ~ 1000 METs-min/week, 650 ~ 1000 METs-min/week, 680 ~ 1000 METs-min/week, respectively. At the same time, we found that when the age exceeded 81 years, even when participating in exercise, it did not achieve the effect of alleviating depressive symptoms in older adults. Conclusions In conclusion, including Walking, AE, Yoga, Qigong, RT, and TC, effectively alleviate depressive symptoms in older adults. Furthermore, we established statistically and clinically significant threshold doses for various exercise types. Early initiation of exercise is beneficial, but its efficacy diminishes from the age of 80, and beyond 81, exercise no longer significantly alleviates depressive symptoms.

Abstract Background Triatomines (kissing bugs) are natural vectors of trypanosomes, which are single-celled parasitic protozoans, such as Trypanosoma cruzi, T. conorhini and T. rangeli. The understanding of the transmission cycle of T. conorhini and Triatoma rubrofasciata in China is not fully known. Methods The parasites in the faeces and intestinal contents of the Tr. rubrofasciata were collected, and morphology indices were measured under a microscope to determine the species. DNA was extracted from the samples, and fragments of 18S rRNA, heat shock protein 70 (HSP70) and glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) were amplified and sequenced. The obtained sequences were then identified using the BLAST search engine, followed by several phylogenetic analyses. Finally, laboratory infections were conducted to test whether Tr. rubrofasciata transmit the parasite to rats (or mice) through bites. Moreover, 135 Tr. rubrofasciata samples were collected from the Guangxi region and were used in assays to investigate the prevalence of trypanosome infection. Results Trypanosoma sp. were found in the faeces and intestinal contents of Tr. rubrofasciata, which were collected in the Guangxi region of southern China and mostly exhibited characteristics typical of epimastigotes, such as the presence of a nucleus, a free flagellum and a kinetoplast. The body length ranged from 6.3 to 33.9 µm, the flagellum length ranged from 8.7 to 29.8 µm, the nucleus index was 0.6 and the kinetoplast length was −4.6. BLAST analysis revealed that the 18S rRNA, HSP70 and gGAPDH sequences of Trypanosoma sp. exhibited the highest degree of similarity with those of T. conorhini (99.7%, 99.0% and 99.0%, respectively) and formed a well-supported clade close to T. conorhini and T. vespertilionis but were distinct from those of T. rangeli and T. cruzi. Laboratory experiments revealed that both rats and mice developed low parasitaemia after inoculation with Trypanosoma sp. and laboratory-fed Tr. rubrofasciata became infected after feeding on trypanosome-positive rats and mice. However, the infected Tr. rubrofasciata did not transmit Trypanosoma sp. to their offspring. Moreover, our investigation revealed a high prevalence of Trypanosoma sp. infection in Tr. rubrofasciata, with up to 36.3% of specimens tested in the field being infected. Conclusions Our study is the first to provide a solid record of T. conorhini from Tr. rubrofasciata in China with morphological and molecular evidence. This Chinese T. conorhini is unlikely to have spread through transovarial transmission in Tr. rubrofasciata, but instead, it is more likely that the parasite is transmitted between Tr. rubrofasciata and mice (or rats). However, there was a high prevalence of T. conorhini in the Tr. rubrofasciata from our collection sites and numerous human cases of Tr. rubrofasciata bites were recorded. Moreover, whether these T. conorhini strains are pathogenic to humans has not been investigated. Graphical Abstract

IntroductionYouhua Kuijie prescription (YHKJ) is a hospital preparation that is composed of nine kinds of herbs. Sulfasalazine (SASP) is widely used as a first-line clinical treatment for UC. Traditional Chinese medicine and Western medicine have their own advantages in the treatment of UC, and the mechanism of YHKJ combined with SASP in the treatment of UC needs to be investigated.MethodsIn this study, the therapeutic mechanism of YHKJ combined with SASP in the treatment of UC was predicted by network pharmacology and molecular docking. The chemical components and related targets of YHKJ were obtained from the TCMSP database. The chemical structure of SASP was obtained from the PubChem server, and related targets of SASP molecules were identified using the PharmMapper database. UC-related targets were obtained from the DisGeNET, GeneCards, OMIM, TTD, DrugBank and PharmGkb databases.ResultsIn total, 197 shared targets were identified by constructing a Venn diagram. PPI network data obtained from the STRING database were imported into Cytoscape to visualize the “drug-disease” target network, and STAT3 was selected as the core target by topological analysis. Gene Ontology revealed the biological functions of target genes, and KEGG analysis revealed that the core target STAT3 was differentially expressed in Th17 cells and the JAK-STAT signaling pathway. Thus, the core target STAT3 was subjected to molecular docking with the top 10 components, including nine YHKJ components (quercetin, luteolin, ursolic acid, daidzein, kaempferol, wogonin, myricetin, formononetin, indirubin) and SASP (C18H14N4O5S). The molecular docking results showed that STAT3 had favorable binding with the nine YHKJ components and SASP; STAT3 had the strongest binding with ursolic acid (−10.26 kcal/mol), followed by SASP (−8.54 kcal/mol). Qualitative analysis of the chemical constituents of YHKJ by HPLC revealed that sitosterol, ursolic acid, myricetin, daidzein, quercetin, kaempferol and formononetin were the main components. Additional experiments verified that YHKJ combined with SASP inhibited activation of the IL-6/JAK2/STAT3 pathway and alleviated inflammation in UC model rats.DiscussionOur results showed that seven chemical components in YHKJ cooperate with SASP to interfere with activation of the IL-6/JAK2/STAT3 pathway, thus playing a role in the treatment of UC.

Abstract Background Intravenous lidocaine could be a potential alternative adjuvant to propofol-based sedation for gastroscopy in elderly patients. This study aimed to evaluate the effect of intravenous lidocaine on the median effective dose (ED50) of propofol induction dose in elderly patients undergoing painless gastroscopy. Methods The study included 70 patients aged ≥ 60 years undergoing painless gastroscopy with 64 randomly assigned to either group L (2% lidocaine 1.5 mg/kg, n = 31) or group N (equal volume normal saline, n = 33). All patients received propofol induction following 0.1 μg/kg intravenous sufentanil. The Dixon “up-and-down” sequential method was used, with a 1.5 mg/kg initial induction dose of propofol followed by a 0.1 mg/kg sequential variable dose. The primary endpoint was the ED50 of the propofol induction dose. The total propofol dose, recovery time, adverse events, and local anesthetic intoxication reactions were also recorded. Results The ED50 of propofol induction dose was 0.670 (95% confidence interval [CI] 0.216–0.827) mg/kg in group L and 1.118 (95% CI 0.803–1.232) mg/kg in group N. There was a statistically significant difference between the two groups (p

Abstract Purpose The pathways underpinning suicide ideation (SI) and certain physical and psychological factors in patients with advanced breast cancer remain unclear. This study develops and validates a mediation model that delineates the associations between several multidimensional variables and SI in Chinese patients with advanced breast cancer. Methods Patients with advanced breast cancer (n = 509) were recruited as study participants from 10 regional cancer centers across China from August 2019 to December 2020. Participants were required to complete five questionnaires using an electronic patient-reported outcomes (ePRO) system: 9 item- Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), 5-level EQ-5D (EQ-5D-5L), and MD Anderson Symptom Inventory (MDASI). Risk factors for SI were identified using multivariable logistic regression, and inputted into serial multiple mediation models to elucidate the pathways linking the risk factors to SI. Results SI prevalence was 22.8% (116/509). After adjusting for covariates, depression (odds ratio [OR] = 1.384), emotional distress (OR = 1.107), upset (OR = 0.842), and forgetfulness (OR = 1.236) were identified as significant independent risk factors (all p

Abstract Metastatic breast cancer could cause various psychological symptoms. Managing Cancer and Living Meaningfully (CALM) is a brief, manualized psychotherapy that has been validated for advanced cancer patients. We conducted a pilot randomized control trial (RCT) to verify the feasibility and preliminary efficacy of CALM therapy in this population. Patients who met the inclusion criteria were randomly assigned into CALM or Wait-list Control (WLC) groups. Patients in the CALM group received CALM therapy and usual care; patients in WLC group first received usual care and then underwent CALM therapy after completing all assessments. All patients were asked to complete three assessments: T0(baseline), T1(3 months), and T2(6 months). The primary outcomes was death anxiety; other outcomes were depression, distress, suicide ideation, attachment security, spiritual well-being and quality of life at the end of life. Analysis of Covariance (ANCOVA) and t-test were used for statistics analysis. Thirty-six patients were randomly assigned to either of the two groups, with 34 patients completing the three assessments. At six months, we found significant between group differences in suicide ideation, distress, and life completion between the CALM and WLC groups. At T2, patients in CALM group reported lower levels of depression (F = 5.016, p = 0.033, partial η2 = 0.143), distress (F = 7.969, p = 0.010, partial η2 = 0.257), attachment avoidance (F = 4.407, p = 0.044, partial η2 = 0.128), and better sense of life completion (F = 5.493, p = 0.026, partial η2 = 0.155) than patients in the WLC group. Compared with results of the T0 assessments, we found significant differences in socres for depression (T2&T0, t = − 2.689, p = 0.011, Cohen’s d = 0.940) and distress (T2&T0, t = − 2.453, p = 0.022, Cohen’s d = 0.965) between the two groups. CALM therapy was well received by the study population, and CALM therapy can reduce depression, distress, attachment avoidance while improving quality of life in Chinese metastatic breast cancer patients. A Phase III RCT was recommended to verify the impact of CALM therapy on psychological burden and survival in this population. Trial registration: This study is part of the “Preliminary application study for Managing Cancer and Living Meaningfully (CALM) therapy in Chinese advanced cancer patients” clinical trial, with the Trial Registration Number of ChiCTR1900023129 (13/05/2019) in the Chinese Clinical Trial Registry (ChiCTR) website. ( https://www.chictr.org.cn/index.html ).

Abstract Background Little is understood about the association between psychosomatic symptoms and advanced cancer among older Chinese patients. Methods This secondary analysis was part of a multicenter cross-sectional study based on an electronic patient-reported outcome platform. Patients with advanced cancer were included between August 2019 and December 2020 in China. Participants (over 60 years) completed the MD Anderson Symptom Inventory (MDASI) and Hospital Anxiety and Depression Scale (HADS) to measure symptom burden. Network analysis was also conducted to investigate the network structure, centrality indices (strength, closeness, and betweenness) and network stability. Results A total of 1022 patients with a mean age of 66 (60–88) years were included; 727 (71.1%) were males, and 295 (28.9%) were females. A total of 64.9% of older patients with advanced cancer had one or more symptoms, and up to 80% had anxiety and depression. The generated network indicated that the physical symptoms, anxiety and depression symptom communities were well connected with each other. Based on an evaluation of the centrality indices, ‘distress/feeling upset’ (MDASI 5) appears to be a structurally important node in all three networks, and ‘I lost interest in my own appearance’ (HADS-D4) had the lowest centrality indices. The network stability was relatively high (> 0.7). Conclusion The symptom burden remains high in older patients with advanced cancer in China. Psychosomatic symptoms are highly interactive and often present as comorbidities. This network can be used to provide targeted interventions to optimize symptom management in older patients with advanced cancer in China. Trial registration Chinese Clinical Trial Registry (ChiCTR1900024957), registered on 06/12/2020.

Abstract Objectives Patients with advanced colorectal cancer (CRC) have multiple concurrent physical and psychological symptoms. This study aimed to explore the relationship between anxiety, depression, and symptom burden in advanced CRC. Methods A multicenter cross‐sectional study was conducted in 10 cancer centers from geographically and economically diverse sites in China. A total of 454 patients with advanced CRC completed the Hospital Anxiety and Depression Scale and the MD Anderson Symptom Inventory. Multiple regression analysis was applied to explore the relationship between anxiety, depression and symptom burden. Results About one‐third of the patients showed symptoms of anxiety or depression. Patients with anxiety or depression reported significantly higher symptom burden than those without (p

Abstract Background The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. Methods In this real‐world study, we enrolled 143 COVID‐19‐vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti‐spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4‐BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. Results Patients with liver cancer receiving booster doses had higher levels of anti‐spike RBD IgG against circulating omicron (BA.4‐BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4‐BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti‐spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti‐spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. Conclusion Our study found that there may be differences in vaccine response and protective effect against COVID‐19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID‐19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

Abstract Background Patients diagnosed with advanced stage cancer face an elevated risk of suicide. We aimed to develop a suicidal ideation (SI) risk prediction model in patients with advanced cancer for early warning of their SI and facilitate suicide prevention in this population. Patients and Methods We consecutively enrolled patients with multiple types of advanced cancers from 10 cancer institutes in China from August 2019 to December 2020. Demographic characteristics, clinicopathological data, and clinical treatment history were extracted from medical records. Symptom burden, psychological status, and SI were assessed using the MD Anderson Symptom Inventory (MDASI), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire‐9 (PHQ‐9), respectively. A multivariable logistic regression model was employed to establish the model structure. Results In total, 2814 participants were included in the final analysis. Nine predictors including age, sex, number of household members, history of previous chemotherapy, history of previous surgery, MDASI score, HADS‐A score, HADS‐D score, and life satisfaction were retained in the final SI prediction model. The model achieved an area under the curve (AUC) of 0.85 (95% confidential interval: 0.82–0.87), with AUCs ranging from 0.75 to 0.95 across 10 hospitals and higher than 0.83 for all cancer types. Conclusion This study built an easy‐to‐use, good‐performance predictive model for SI. Implementation of this model could facilitate the incorporation of psychosocial support for suicide prevention into the standard care of patients with advanced cancer.

Abstract Several lines of evidence support the involvement of transcriptomic and epigenetic mechanisms in the brain structural deficits of major depressive disorder (MDD) separately. However, research in these two areas has remained isolated. In this study, we proposed an integrative strategy that combined neuroimaging, brain-wide gene expression, and peripheral DNA methylation data to investigate the genetic basis of gray matter abnormalities in MDD. The MRI T1-weighted images and Illumina 850 K DNA methylation microarrays were obtained from 269 patients and 416 healthy controls, and brain-wide transcriptomic data were collected from Allen Human Brain Atlas. The between-group differences in gray matter volume (GMV) and differentially methylated CpG positions (DMPs) were examined. The genes with their expression patterns spatially related to GMV changes and genes with DMPs were overlapped and selected. Using principal component regression, the associations between DMPs in overlapped genes and GMV across individual patients were investigated, and the region-specific correlations between methylation status and gene expression were examined. We found significant associations between the decreased GMV and DMPs methylation status in the anterior cingulate cortex, inferior frontal cortex, and fusiform face cortex regions. These DMPs genes were primarily enriched in the neurodevelopmental and synaptic transmission process. There was a significant negative correlation between DNA methylation and gene expression in genes associated with GMV changes of the frontal cortex in MDD. Our findings suggest that GMV abnormalities in MDD may have a transcriptomic and epigenetic basis. This imaging-transcriptomic-epigenetic integrative analysis provides spatial and biological links between cortical morphological deficits and peripheral epigenetic signatures in MDD.

Abstract Background Clonorchiasis remains a non-negligible global zoonosis, causing serious socioeconomic burdens in endemic areas. Clonorchis sinensis infection typically elicits Th1/Th2 mixed immune responses during the course of biliary injury and periductal fibrosis. However, the molecular mechanism by which C. sinensis juvenile initially infects the host remains poorly understood. Methods The BALB/c mouse model was established to study early infection (within 7 days) with C. sinensis juveniles. Liver pathology staining and observation as well as determination of biochemical enzymes, blood routine and cytokines in blood were conducted. Furthermore, analysis of liver transcriptome, proteome and metabolome changes was performed using multi-omics techniques. Statistical analyses were performed using Student's t-test. Results Histopathological analysis revealed that liver injury, characterized by collagen deposition and inflammatory cell infiltration, occurred as early as 24 h of infection. Blood indicators including ALT, AST, WBC, CRP and IL-6 indicated that both liver injury and systemic inflammation worsened as the infection progressed. Proteomic data showed that apoptosis and junction-related pathways were enriched within 3 days of infection, indicating the occurrence of liver injury. Furthermore, proteomic and transcriptomic analysis jointly verified that the detoxification and antioxidant defense system was activated by enrichment of glutathione metabolism and cytochrome P450-related pathways in response to acute liver injury. Proteomic-based GO analysis demonstrated that biological processes such as cell deformation, proliferation, migration and wound healing occurred in the liver during the early infection. Correspondingly, transcriptomic results showed significant enrichment of cell cycle pathway on day 3 and 7. In addition, the KEGG analysis of multi-omics data demonstrated that numerous pathways related to immunity, inflammation, tumorigenesis and metabolism were enriched in the liver. Besides, metabolomic screening identified several metabolites that could promote inflammation and hepatobiliary periductal fibrosis, such as CA7S. Conclusions This study revealed that acute inflammatory injury was rapidly triggered by initial infection by C. sinensis juveniles in the host, accompanied by the enrichment of detoxification, inflammation, fibrosis, tumor and metabolism-related pathways in the liver, which provides a new perspective for the early intervention and therapy of clonorchiasis. Graphical Abstract

Summary: Cell therapy using proliferating human hepatocytes (ProliHHs) is an effective treatment approach for advanced liver diseases. However, rapid and accurate identification of high-quality ProliHHs from different donors is challenging due to individual heterogeneity. Here, we developed a machine learning framework to integrate single-cell Raman spectroscopy from multiple donors and identify different stages of ProliHHs. A repository of more than 14,000 Raman spectra, consisting of primary human hepatocytes (PHHs) and different passages of ProliHHs from six donors, was generated. Using a sliding window algorithm, potential biomarkers distinguishing the different cell stages were identified through differential analysis. Leveraging machine learning models, accurate classification of cell stages was achieved in both within-donor and cross-donor prediction tasks. Furthermore, the study assessed the relationship between donor and cell numbers and its impact on prediction accuracy, facilitating improved quality control design. A similar workflow can also be extended to encompass other cell types.

IntroductionThe programmed cell death (PCD) pathway plays an important role in restricting cancer cell survival and proliferation. However, limited studies have investigated the association between genetic variants in the 3′-untranslated region of the PCD pathway genes and breast cancer outcomes.MethodsIn this study, we genotyped 28 potentially functional single nucleotide polymorphisms (SNPs) in 23 PCD pathway genes in 1,177 patients with early-stage breast cancer (EBC) from a Han Chinese population. The median follow-up period was 174 months.ResultsAmong all the candidate SNPs, four independent SNPs (rs4900321 and rs7150025 in ATG2B, rs6753785 in BCL2L11, and rs2213181 in c-Kit) were associated with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer-specific survival (BCSS) and overall survival (OS), respectively. Further combined genotypes of these four SNPs revealed that the survival decreased as the number of unfavorable genotypes increased (Ptrend = 1.0 × 10−6, 8.5 × 10−8, 3.6 × 10−4, and 1.3 × 10−4 for iDFS, DDFS, BCSS, and OS, respectively). Receiver operating characteristic curve analysis demonstrated that incorporating unfavorable genotypes and clinicopathological variables improved the ability to predict EBC survival (P = 0.006, 0.004, 0.029, and 0.019 for iDFS, DDFS, BCSS, and OS, respectively). Additionally, rs6753785 and rs2213181 were associated with BCL2L11 and c-Kit mRNA expression, respectively.ConclusionsOur results suggest that these four SNPs may act as novel biomarkers for EBC survival, possibly by modulating the expression of the corresponding genes.

Terpene synthases (TPSs) regulate plant growth, development, and stress response. TPS genes have been identified in Arabidopsis thaliana and Zea mays. Cannabis sativa TPS genes were identified and analyzed using bioinformatics. Genomic data were downloaded from Plant Transcription Factor Database and National Center for Biotechnology Information database, and TPS genes were predicted, analyzed, and visualized using ExPASy, PlantCare, and other online websites along with TBtools, MEGA software, and other software. To verify its role, quantitative real-time polymerase chain reaction (qRT-PCR) tests were conducted. The Cannabis sativa TPS family comprises 41 elements distributed over 8 chromosomes and a single scaffold segment. The isoelectric point varied between 4.96 and 7.03, while the molecular weight spanned from 20705.90 to 102324.64 Da. The majority of genes were found in the cytoplasm and chloroplasts, with the remainder situated in the peroxisome, nucleus, plasma membrane, and mitochondria. Several cis-acting components associated with stress response were present in the gene's upstream promoter region. Data from RNA sequencing and qRT-PCR revealed specific expression of TPS genes in all five organs of female Cannabis sativa plants. Collinearity analysis showed 4 homologous gene pairs between the Cannabis sativa and Arabidopsis thaliana, with many pairs of homologous genes in other species, which was consistent with the dicotyledons evolutionary relationship. Furthermore, some genes may participate in Cannabis sativa growth and development and play a role in secondary metabolite synthesis. Therefore, bioinformatics analysis of the Cannabis sativa TPS gene family provides a theoretical basis for future research on the volatile terpene compounds of Cannabis sativa.

Abstract Background Oculocutaneous albinism type 4 (OCA4) is a rare autosomal recessive disorder characterized by a reduction of pigmentation in skin, hair, and eyes, and OCA4 is mainly seen in the SLC45A2 gene variants. Objective To report a Chinese patient suspected of oculocutaneous albinism and identify the causing mutation. Methods Genomic DNA was extracted from the peripheral blood samples of the patient, his parents, and elder brother. Whole exome sequencing was performed in the family, and Sanger sequencing was then used to verify the mutations. Results Compound heterozygous variants, c.1304C>A (p.S435Y) and c.301C>G (p.R101G) in SLC45A2 gene, were detected in the proband, which were inherited from his father and mother respectively. Based on the ACMG guidelines, we can interpret the c.1304C>A (p.S435Y) variant as a suspected pathogenic variant and the c.301C>G (p.R101G) variant as a clinically significant unspecified variant. The diagnosis of OCA4 is confirmed. Conclusion We firstly reported this case of OCA4 with the compound heterozygous variants in the SLC45A2 gene. Our findings further enrich the reservoir of SLC45A2 mutations in OCA4.

Abstract Background Ji Chuan Jian (JCJ), a classic Traditional Chinese Medicine (TCM) formula, has been widely applied in treating Parkinson’s disease (PD) in China, However, the interaction of bioactive compounds from JCJ with the targets involved in PD remains elusive. Methods Based on the transcriptome sequencing and network pharmacology approaches, the chemical compounds of JCJ and gene targets for treating PD were identified. Then, the Protein-protein interaction (PPI) and “Compound-Disease-Target” (C-D-T) network were constructed by using of Cytoscape. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to these target proteins. Finally, AutoDock Vina was used for applying molecular docking. Results In the present study, a total number of 2669 differentially expressed genes (DEGs) were identified between PD and healthy controls using whole transcriptome RNA sequencing. Then, 260 targets of 38 bioactive compounds in JCJ were identified. Of these targets, 47 were considered PD-related targets. Based on the PPI degree, the top 10 targets were identified. In C-D-T network analysis, the most important anti-PD bioactive compounds in JCJ were determined. Molecular docking revealed that potential PD-related targets, matrix metalloproteinases-9 (MMP9) were more stably bound with naringenin, quercetin, baicalein, kaempferol and wogonin. Conclusion Our study preliminarily investigated the bioactive compounds, key targets, and potential molecular mechanism of JCJ against PD. It also provided a promising approach for identifying the bioactive compounds in TCM as well as a scientific basis for further elucidating the mechanism of TCM formulae in treating diseases.

Abstract A more effective and better-tolerated site for repetitive transcranial magnetic stimulation (rTMS) for treating cognitive dysfunction in patients with bipolar disorder (BD) is needed. The primary visual cortex (V1) may represent a suitable site. To investigate the use of the V1, which is functionally linked to the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), as a potential site for improving cognitive function in BD. Seed-based functional connectivity (FC) analysis was used to locate targets in the V1 that had significant FC with the DLPFC and ACC. Subjects were randomly assigned to 4 groups, namely, the DLPFC active-sham rTMS (A1), DLPFC sham-active rTMS (A2), ACC active-sham rTMS (B1), and ACC sham-active rTMS groups (B2). The intervention included the rTMS treatment once daily, with five treatments a week for four weeks. The A1 and B1 groups received 10 days of active rTMS treatment followed by 10 days of sham rTMS treatment. The A2 and B2 groups received the opposite. The primary outcomes were changes in the scores of five tests in the THINC-integrated tool (THINC-it) at week 2 (W2) and week 4 (W4). The secondary outcomes were changes in the FC between the DLPFC/ACC and the whole brain at W2 and W4. Of the original 93 patients with BD recruited, 86 were finally included, and 73 finished the trial. Significant interactions between time and intervention type (Active/Sham) were observed in the scores of the accuracy of the Symbol Check in the THINC-it tests at baseline (W0) and W2 in groups B1 and B2 (F = 4.736, p = 0.037) using a repeated-measures analysis of covariance approach. Group B1 scored higher in the accuracy of Symbol Check at W2 compared with W0 (p

Background: The type of anaesthesia and choice of anaesthetic drugs may affect the quality of recovery after surgery. Remimazolam is a new benzodiazepine with rapid onset and offset, specifically antagonised by flumazenil. This study aimed to compare remimazolam with propofol on the quality of recovery in patients undergoing ambulatory arthroscopic surgery. Methods: Patients aged 18–65 yr and scheduled for ambulatory arthroscopic meniscus repair were recruited and randomly assigned to receive either continuous i.v. infusion of remimazolam or plasma target-controlled infusion of propofol. The quality of recovery-15 (QoR-15) scale was administered on postoperative day 1 (POD1) as the primary outcome. Secondary outcomes included the Athens Insomnia Scale (AIS) scores and cardiovascular variables. Results: In total, 120 patients were randomly assigned to the remimazolam or propofol groups and 114 patients were included in the analysis. The remimazolam group had higher total QoR-15 scores on POD1 (125 [120–127.5] vs 121.5 [119–124], with a median difference of 3 (95% confidence interval: 1–5; P=0.002). Physical independence and psychological support were higher in the remimazolam group (8.5 [8–10] vs 8 [7–9], P=0.043; 17 [13–17] vs 12.5 [12–14], P

Abstract Background Schizophrenia (SZ) arises from a complex interplay involving genetic and molecular factors. Early intervention of SZ hinges upon understanding its vulnerability and resiliency factors in study of SZ and genetic high risk for SZ (GHR). Methods Herein, using integrative and multimodal strategies, we first performed a longitudinal study of neural function as measured by amplitude of low frequency function (ALFF) in 21 SZ, 26 GHR, and 39 healthy controls to characterize neurodevelopmental trajectories of SZ and GHR. Then, we examined the relationship between polygenic risk score for SZ (SZ-PRS), lipid metabolism, and ALFF in 78 SZ, and 75 GHR in cross-sectional design to understand its genetic and molecular substrates. Results Across time, SZ and GHR diverge in ALFF alterations of the left medial orbital frontal cortex (MOF). At baseline, both SZ and GHR had increased left MOF ALFF compared to HC (P

Parasitic diseases pose a significant threat to global public health, particularly in developing countries. Host genetic factors play a crucial role in determining susceptibility and resistance to infection. Recent advances in molecular and biological technologies have enabled significant breakthroughs in understanding the impact of host genes on parasite adaptation. In this comprehensive review, we analyze the host genetic factors that influence parasite adaptation, including hormones, nitric oxide, immune cells, cytokine gene polymorphisms, parasite-specific receptors, and metabolites. We also establish an interactive network to better illustrate the complex relationship between host genetic factors and parasite-host adaptation. Additionally, we discuss future directions and collaborative research priorities in the parasite-host adaptation field, including investigating the impact of host genes on the microbiome, developing more sophisticated models, identifying and characterizing parasite-specific receptors, utilizing patient-derived sera as diagnostic and therapeutic tools, and developing novel treatments and management strategies targeting specific host genetic factors. This review highlights the need for a comprehensive and systematic approach to investigating the underlying mechanisms of parasite-host adaptation, which requires interdisciplinary collaborations among biologists, geneticists, immunologists, and clinicians. By deepening our understanding of the complex interactions between host genetics and parasite adaptation, we can develop more effective and targeted interventions to prevent and treat parasitic diseases. Overall, this review provides a valuable resource for researchers and clinicians working in the parasitology field and offers insights into the future directions of this critical research area.

ObjectiveWe conducted this cross-sectional study to explore the mediating and predicting role of somatic symptom disorder (SSD) between psychological measures and quality of life (QOL) among Chinese breast cancer patients.MethodsBreast cancer patients were recruited from three clinics in Beijing. Screening tools included the Patient Health Questionnaire-15 (PHQ-15), the Patient Health Questionnaire-9 (PHQ-9), the General Anxiety Disorder-7 scale (GAD-7), the Health Anxiety Scale (Whiteley Index-8, WI-8), the Somatic Symptom Disorder B-Criteria Scale (SSD-12), the Fear of Cancer Recurrence scale (FCR-4), the Brief Illness Perception Questionnaire (BIPQ-8), and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Chi-square tests, nonparametric tests, mediating effect analysis, and linear regression analysis were used for the data analysis.ResultsAmong the 264 participants, 25.0% were screened positive for SSD. The patients with screened positive SSD had a lower performance status, and a greater number of patients with screened positive SSD received traditional Chinese medicine (TCM) (p

The preparation of pH-responsive nanocontainers by typical silane modification of the mesoporous silica nanoparticle (MSN) surface is usually high-cost, complex, and time-consuming, which remains a great challenge for effective corrosion protection of magnesium alloy. Here, a new strategy to construct pH-responsive nanocontainers (MSN-MBT@LDH) is demonstrated. The nanocontainers consist of corrosion inhibitor (2-mercaptobenzothiazole, MBT) loaded MSN core and layered double hydroxide (LDH) nanosheet shell serving as gatekeepers. The successful loading of MBT and encapsulation by LDH nanosheets were confirmed by a series of characterization such as scanning transmission electron microscopy coupled with energy dispersive X-ray spectroscopy (STEM-EDS) and N2 adsorption/desorption isotherms. The pH-responsive feature of the nanocontainers was demonstrated by determination of the MBT concentration in buffer solutions with different pH values. A smart corrosion protection system on Mg alloy is obtained by incorporating the synthesized nanocontainers into a self-assembled nanophase particle (SNAP) coating. The electrochemical tests and visual observations show that the hybrid coating has the best barrier properties and robustness in corrosion protection in NaCl corrosive solutions in comparison with the control coatings. The present method simplifies the synthesis processes of nanocontainers and eliminates the potential detrimental effect of excess gatekeepers on the coating. The findings provide new insights into the preparation of scalable nanocontainers. The self-healing coatings are expected to have widespread applications for corrosion protection of Mg alloy and other metals.

For mangroves that would terrestrialize rather than be submerged by the rising sea, concerns should be drawn to the attention of their community, which is crucial for maintaining the ecological functions of mangrove wetlands. However, community studies have traditionally relied on observed local diversity but have neglected dark diversity. Previously ignored dark diversity may hold more information, particularly in urban mangroves that are being terrestrialized or restored. To this end, in urban mangrove monitoring experiments in South China, North Indo-Pacific, we first proposed an index to evaluate mangrove terrestrialization trends. We then estimated the probabilistic site-specific species pool and dark diversity based on the co-occurrence data extracted using an unmanned aerial vehicle (UAV) system in a typical terrestrialized urban mangrove. Combining the observed and dark diversity, we explored community composition and potential changes in the mangrove forest. The results showed that urban mangroves with sufficient sediment supply were terrestrializing and would gradually continue in the future. The terrestrialization indices were predicted to first increase and then decrease until the 2100 s. All six currently recorded mangrove species will not become extinct in a typical forest. Acanthus ilicifolius had the highest distribution probability, with an average value of 0.99, whereas the smallest probability was 0.19 for Sonneratia caseolaris. The currently dominant Kandelia obovata community can potentially be replaced by Avicennia marina–Aegiceras corniculatum community, and the lower layer of the mangrove forests will be consistently covered by A. ilicifolius. Specifically, K. obovata was distributed across 98.51% of the forest, of which 85.48% of its distribution probability will decline. Except for its current in-situ areas, an extra 67.19% of the forest will be covered by A. marina. A. ilicifolius covered nearly 94.64% of the current forest lower layer, of which 94.17% had a high potential to remain in situ. This study enhances our understanding of the response of mangroves to rising sea levels due to global climate change.

Abstract The associations between functional traits and species distributions across environments have attracted increasing interest from ecologists and can enhance knowledge about how plants respond to the environments. Here, we applied a hierarchical generalized linear model to quantifying the role of functional traits in plant occurrence across topographic gradients. Functional trait data, including specific leaf area, maximum height, seed mass and stem wood density, together with elevation, aspect and slope, were used in the model. In our results, species responses to elevation and aspect were modulated by maximum height and seed mass. Generally, shorter tree species showed positive responses to incremental elevation, while this trend became negative as the maximum height exceeded 22 m. Most trees with heavy seeds (> 1 mg) preferred more southerly aspects where the soil was drier, and those light-seed trees were opposite. In this study, the roles of maximum height and seed mass in determining species distribution along elevation and aspect gradients were highlighted where plants are confronted with low-temperature and soil moisture deficit conditions. This work contributes to the understanding of how traits may be associated with species occurrence along mesoscale environmental gradients.

Abstract Background Inhibitors targeting immune checkpoints, such as PD-1/PD-L1 and CTLA-4, have prolonged survival in small groups of non-small cell lung cancer (NSCLC) patients, but biomarkers predictive of the response to the immune checkpoint inhibitors (ICIs) remain rare. Methods The nonnegative matrix factorization (NMF) was performed for TCGA-NSCLC tumor samples based on the LM22 immune signature to construct subgroups. Characterization of NMF subgroups involved the single sample gene set variation analysis (ssGSVA), and mutation/copy number alteration and methylation analyses. Construction of RNA interaction network was based on the identification of differentially expressed RNAs (DERs). The prognostic predictor was constructed by a LASSO-Cox regression model. Four GEO datasets were used for the validation analysis. Results Four immune based NMF subgroups among NSCLC patients were identified. Genetic and epigenetic analyses between subgroups revealed an important role of somatic copy number alterations in determining the immune checkpoint expression on specific immune cells. Seven hub genes were recognized in the regulatory network closely related to the immune phenotype, and a three-gene prognosis predictor was constructed. Conclusions Our study established an immune-based prognosis predictor, which might have the potential to select subgroups benefiting from the ICI treatment, for NSCLC patients using publicly available databases.

ABSTRACT Cholestasis is characterized by bile acid (BA) circulation disorders, which is usually related to damage of hepatocyte barrier function. Currently, patients with cholestasis face several obstacles in seeking diagnosis and therapy. Da-Huang-Xiao-Shi decoction (DHXSD) is an ancient classic formula that has been used clinically for cholestasis treatment. Nevertheless, the underlying biological activities and therapeutic mechanisms remain unclear. In this study, an alpha-naphthylisothiocyanate (ANIT)-induced cholestasis rat model was established to examine the anticholestatic effects of DHXSD using histopathological and molecular analyses. Transcriptomic analysis combined with 16S rRNA gene sequencing analysis was systematically applied to study the mechanism of action of DHXSD. Simultaneously, the effect of DHXSD on gut microbiota, short-chain fatty acids (SCFAs), and intestinal barrier function were evaluated based on the ANIT-induced cholestasis model in rats. The results showed that DHXSD effectively attenuated ANIT-induced cholestasis by reducing liver function indicators (alanine transaminase [ALT], P < 0.05; alkaline phosphatase [ALP], P < 0.05; total bile acid [TBA], P < 0.01; γ-glutamyl transpeptidase [GGT], P < 0.001) and levels of hepatotoxicity-related enzymes (P < 0.05), thus improving the recovery of histopathological injuries, and regulating levels of inflammatory cytokines (P < 0.05). In addition, 16S rRNA gene sequencing analysis combined with intestinal barrier function analysis revealed that the DHXSD significantly ameliorated ANIT-induced gut microbiota dysbiosis. Significantly altered genes in the model and treatment groups were screened using transcriptomic analysis. Sixty-eight genes and four microbial genera were simultaneously altered with opposing trends in variation after ANIT and DHXSD treatments. We built a framework for predicting targets and host-microbe interaction mechanisms, as well as identifying alternative treatment for cholestasis, which should be validated further for clinical application. In conclusion, DHXSD appears to be a promising agent for protection against liver injury. IMPORTANCE Cholestasis is a serious manifestation of liver diseases resulting in liver injury, fibrosis, and liver failure with limited therapies. To date, only ursodeoxycholic acid (UDCA) has been approved by the U.S. Food and Drug Administration for the treatment of cholestasis. However, approximately one-third of patients with cholestasis are unresponsive to UDCA. Therefore, it is urgent to search for appropriate therapeutic agents for restoring stoppage status of the bile components to treat cholestasis. In this study, we investigated how the microbiome and transcriptome data sets correlated with each other to clarify the role of microbiome alterations in host metabolism. In combination, this research offers potential molecular biomarkers that should be validated for more accurate diagnosis of cholestasis and the clinical utilisation of gut microbiota as a target for treatment.

IntroductionMunro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA methylation microenvironment of Munro's microabscess and the crosstalk with transcription and its effect on neutrophils have not yet been revealed.MethodsPerformed genome-wide DNA methylation analysis and further differential methylation analysis of psoriatic skin lesions with and without Munro's microabscess from two batch samples consisting of 114 former samples in the discovery stage and 21 newly-collected samples in the validation stage. Utilized GO, MEME, and other tools to conduct downstream analysis on differentially methylated sites (DMSs). Correlation analysis of methylation level and transcriptome data was also conducted.ResultsWe observed 647 overlapping DMSs associated with Munro's microabscess. Subsequently, GO pathway analysis revealed that DNA methylation might affect the physical properties associated with skin cells through focal adhesion and cellsubstrate junction and was likely to recruit neutrophils in the epidermis. Via the MEME tool, used to investigate the possible binding transcription factors (TFs) of 20 motifs around the 647 DMSs, it was found that DNA methylation regulated the binding of AP1 family members and the recruitment of neutrophils in the epidermis through the TGF-beta pathway and the TH17 pathway. Meanwhile, combined with our earlier transcriptome data, we found DNA methylation would regulate the expressions of CFDP, SIRT6, SMG6, TRAPPC9, HSD17B7, and KIAA0415, indicating these genes would potentially promote the process of Munro's microabscess.DiscussionIn conclusion, DNA methylation may affect the course of psoriasis by regulating the progression of Munro's microabscess in psoriatic skin lesions.

An increased incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has been reported in many countries. However, the prevalence and impact factors of psychological distress and resilience in patients with GEP-NETs are unclear. We recruited 200 patients with GEP-NETs to assess psychological distress and resilience. Measures comprised the Distress Thermometer, the Hospital Anxiety and Depression Scale, Connor-Davidson Resilience scale and Medical Coping Modes Questionnaire. Our results found that the prevalence of distress, anxiety, depression and low resilience were 31.5%, 31%, 17.8%, and 25.9%, respectively. Female patients were more likely to be distressed, as were those with NET Grade 1, were partly aware of diagnosis, and had known the diagnosis less than 3 months. Distress positively correlated with acceptance-resignation, and resilience positively correlated with confrontation and avoidance. Resilience negatively correlated with psychological distress. Patients coping disease with acceptance-resignation had higher odds of anxiety, depression, and low resilience. Our findings indicate that psychological distress and low resilience were common in patients with GEP-NETs. This suggests a need to integrate psychosocial domain into GEP-NETs clinical practice.

Non-motor symptoms (NMS) of Parkinson's disease (PD), such as constipation, sleep disorders, and olfactory deficits, may emerge up to 20 years earlier than motor symptoms. A series of evidence indicates that the pathology of PD may occur from the gastrointestinal tract to the brain. Numerous studies support that the gut microbiota communicates with the brain through the immune system, special amino acid metabolism, and the nervous system in PD. Recently, there is growing recognition that the gut microbiota plays a vital role in the modulation of multiple neurochemical pathways via the “gut microbiota-brain axis” (GMBA). Many gut microbiota metabolites, such as fatty acids, amino acids, and bile acids, convey signaling functions as they mediate the crosstalk between gut microbiota and host physiology. Amino acids' abundance and species alteration, including glutamate and tryptophan, may disturb the signaling transmission between nerve cells and disrupt the normal basal ganglia function in PD. Specific amino acids and their receptors are considered new potential targets for ameliorating PD. The present study aimed to systematically summarize all available evidence on the gut microbiota-derived amino acid metabolism alterations associated with PD.

Mitral valve prolapse (MVP) is a prevalent cardiac disorder that impacts approximately 2% to 3% of the overall population. While most patients experience a benign clinical course, there is evidence suggesting that a subgroup of MVP patients face an increased risk of sudden cardiac death (SCD). Although a conclusive causal link between MVP and SCD remains to be firmly established, various factors have been associated with arrhythmic mitral valve prolapse (AMVP). This study aims to provide a comprehensive review encompassing the historical background, epidemiology, pathology, clinical manifestations, electrocardiogram (ECG) findings, and treatment of AMVP patients. A key focus is on utilizing multimodal imaging techniques to accurately diagnose AMVP and to highlight the role of mitral annular disjunction (MAD) in AMVP.

Abstract To facilitate the extraction of source image information, and preserve the consistency of heterogeneous regional features, a multiscale image fusion method based on a joint cascaded convolutional coding network (JCa2Co) is proposed. The JCa2Co network can retain vast quantities of information from source images in a multiscale perspective. The approach includes an encoder, a fusion layer and decoder. In the fusion layer, the Fuzzy Regional Characteristics (FRC) scheme is considered, and the multiscale feature maps are extracted from image subregions to ensure regional image consistency. Firstly, a joint cascaded encoder is used to extract multiscale features of the source image, in which the output of each layer is connected to every other layer. The fusion layer based on FRC is then performed to fuse each scale feature. Finally, the fused image is reconstructed by the decoder. In addition, to verify the regional consistency of the fused image, a regional consistency measure is proposed. Experiments are performed on the TNO Image Fusion Database. The experimental results exhibit that the proposed JCa2Co method has better comprehensive performance than the eight state‐of‐the‐art fusion methods. Moreover, it can effectively integrate meaningful information in infrared and visible images and has excellent performance in objective evaluation and visual quality, which is beneficial to target recognition and tracking.

Abstract Background Cell pyroptosis has been characterized by cell swelling and pro-inflammatory factors release to aggravate inflammatory reaction., such as interlukin-1 beta (IL-1β) and interlukin18 (IL-18). However, the function of famotidine, an antagonist of histamine H2-receptor antagonists, in cell pyroptosis remained unknown. Methods Real-time quantitative PCR (qPCR), western blotting (WB), LDH release assay and enzyme linked immunosorbent assay (Elisa) combined with inhibitor were performed to analyze the effect of famotidine on cell pyroptosis-related gene expression. Results In this study, we found that famotidine (300 μm) treatment led to a phenomenon of cell pyroptosis as confirmed by LDH assay. Further results showed that famotidine triggered cell pyroptosis in gastric cancer cells by activation of NLPR3 inflammasomes including ASC, Caspase-1 and NLRP, leading to enhanced IL-18, not IL-1β, mature and secretion. What’s more, the results also showed GSDME, not GSDMD, was increased in response to famotidine stimulation in BGC823 and AGS cells. Mechanically, phosphorylation of ERK1/2 was drastically enhanced in present with famotidine treatment, while inhibition of ERK1/2 activity by U0126 could reverse the promotion of famotidine in IL-18 secretion. Conclusion These findings revealed a novel role of famotidine in cell pyroptosis in patients with gastric cancer, a comprehensive consideration is needed in treatment of gastric cancer.

Accurate information on cropland evapotranspiration (ET) can facilitate effective agricultural management. However, the application of existing physical models over broad regions may be impeded due to the need for difficult to acquire information about environmental factors that constrain ET. The recently developed near-infrared reflectance of vegetation (NIRv), which can reasonably characterize ecosystem photosynthesis without the need for additional environmental information, is potentially useful for estimating cropland ET and reducing the difficulty in ET modeling. As such, we proposed two simply formulated semi-empirical models that utilize NIRv as a major factor constraining cropland ET. The first model, termed Penman–Monteith+ (PM+), computed canopy transpiration using the PM equation along with canopy conductance values estimated from NIRv-derived gross primary productivity (NIRv-GPP) and calculated soil evaporation using an empirical approach. Another model, termed underlying water-use efficiency+ (uWUE+), used the uWUE approach along with the NIRv-GPP to predict ET. We calibrated and validated PM+ and uWUE+ over 32 cropland flux sites and then compared them with six complex models. The better model between PM+ and uWUE+ was applied to estimate regional ET over North China Plain (NCP), where typical C3 and C4 crops were planted during 2010–2018, along with remote sensing and meteorological data. Results indicated that the two new models can reasonably estimate cropland ET. The PM+ model reproduced an eight-day value of ET (denoted as eight-day ET) with R2 = 0.741 and RMSE = 5.638 mm/8d, slightly better than the uWUE+ model (R2 = 0. 674 and RMSE = 6.275 mm/8d) for a cross-site validation over 17 flux sites of the validation dataset. Site-level validation revealed consistently better performance of PM+ compared to uWUE+ over most flux sites. For the comparisons with six existing models, PM+ can perform better than all these models and uWUE+ is better than five of them. Subsequently, the PM+ (uWUE+) model reasonably reproduced eight-day ET over four sites under a dry climate (Arid Index ≤ 0.5) with site-level R2 = 0.691 (0.617) and RMSE = 6.663 (7.906) mm/8d on average, which is better than the six existing models. In addition, the regional mean annual ET varied from 590 mm per year (mm/yr) to 680 mm/yr over NCP with a significant increasing trend of 9.05 mm/yr (p

Objective: Propofol is the most widely administered intravenous anesthetic to induce deep sedation for gastroscopy procedures. Coadministration of nalbuphine can provide analgesia and sedation to patients experiencing visceral pain, thereby decreasing the amount of propofol needed and reducing the risk of propofol-induced adverse events. We carried out this study to determine the median effective dose (ED50) of propofol in combination with different dosages of nalbuphine and the optimal dosage of nalbuphine during painless gastroscopy.Methods: We recruited sixty-five patients aged 18–60 years who underwent elective painless gastroscopy. A total of sixty-one patients were allocated randomly to the N1 group (nalbuphine 0.1 mg/kg) or N2 group (nalbuphine 0.15 mg/kg). Three minutes after administration of nalbuphine, patients received a preset dose of propofol at 2.0 mg/kg with a dose gradient of 0.2 mg/kg according to Dixon’s “up-and-down” method. The primary outcome was the ED50 of propofol in combination with nalbuphine. Hemodynamic parameters, recovery time, pain score, and adverse events were recorded as secondary outcomes.Results: The ED50 of propofol in the N2 group was significantly lower than that observed in the N1 group (p < 0.01). Using probit analysis, the ED50 and ED95 of propofol were 1.632 mg/kg and 2.759 mg/kg in the N1 group and 1.111 mg/kg and 2.243 mg/kg in the N2 group, respectively. The incidence of hypotension in the N2 group was lower than that in the N1 group (p < 0.05), and the recovery time was shorter than that of the N1 group (p < 0.05).Conclusion: In adult patients, 0.15 mg/kg nalbuphine led to a significant reduction in the ED50 and ED95 of propofol during gastroscopy. This dose of nalbuphine also reduced the incidence of hypotension and shortened the recovery time. Therefore, nalbuphine (0.15 mg/kg) combined with propofol is a safe option for enhancing recovery after painless gastroscopy in adult patients.Clinical Trial Registration: [https://www.chictr.org.cn/edit.aspx?pid=126699&htm=4], identifier [ChiCTR2100053204].

BackgroundCurrently, inflammatory bowel disease (IBD) has become a global chronic idiopathic disease with ever-rising morbidity and prevalence. Accumulating evidence supports the IBD-hygiene hypothesis that helminths and their derivatives have potential therapeutic value for IBD. Clonorchis sinensis (C. sinensis) mainly elicit Th2/Treg-dominated immune responses to maintain long-term parasitism in the host. This study aimed to evaluate the therapeutic effects of cysteine protease (CsCP) and adult crude antigen (CsCA) of C. sinensis, and C. sinensis (Cs) infection on DSS-induced colitis mice.MethodsBALB/c mice were given 5% DSS daily for 7 days to induce colitis. During this period, mice were treated with rCsCP, CsCA or dexamethasone (DXM) every day, or Cs infection which was established in advance. Changes in body weight, disease activity index (DAI), colon lengths, macroscopic scores, histopathological findings, myeloperoxidase (MPO) activity levels, regulatory T cell (Treg) subset levels, colon gene expression levels, serum cytokine levels, and biochemical indexes were measured.ResultsCompared with Cs infection, rCsCP and CsCA alleviated the disease activity of acute colitis more significant without causing abnormal blood biochemical indexes. In comparison, rCsCP was superior to CsCA in attenuating colonic pathological symptoms, enhancing the proportion of Treg cells in spleens and mesenteric lymph nodes, and improving the secretion of inflammatory-related cytokines (e.g., IL-2, IL-4, IL-10 and IL-13) in serum. Combined with RNA-seq data, it was revealed that CsCA might up-regulate the genes related to C-type lectin receptor and intestinal mucosal repair related signal pathways (e.g., Cd209d, F13a1 and Cckbr) to reduce colon inflammation and benefit intestinal mucosal repair. Dissimilarly, rCsCP ameliorated colitis mainly through stimulating innate immunity, such as Toll like receptor (TLR) signaling pathway, down-regulating the expression of inflammatory cytokines (e.g., IL-12b, IL-23r and IL-7), thereby restraining the differentiation of Th1/Th17 cells.ConclusionsBoth rCsCP and CsCA showed good therapeutic effects on the treatment of acute colitis, but rCsCP is a better choice. rCsCP is a safe, effective, readily available and promising therapeutic agent against IBD mainly by activating innate immunity and regulating the IL-12/IL-23r axis.

Osteoporosis affects around 200 million people globally, with menopausal women accounting for the bulk of cases. In the occurrence and development of osteoporosis, a key role is played by osteoclasts. Excessive osteoclast-mediated bone resorption activity reduces bone mass and increases bone fragility, resulting in osteoporosis. Thus, considerable demand exists for designing effective osteoporosis treatments based on targeting osteoclasts. Eltanexor (Elt; KPT-8602) is a selective nuclear-export inhibitor that covalently binds to and blocks the function of the nuclear-export protein exportin-1 (XPO1), which controls the nucleus-to-cytoplasm transfer of certain critical proteins related to growth regulation and tumor suppression, such as p53, IκBα [nuclear factor-κB (NF-κB) inhibitor α] and FOXO1; among these proteins, IκBα, a critical component of the NF-κB signaling pathway that primarily governs NF-κB activation and transcription. How Elt treatment affects osteoclasts remains poorly elucidated. Elt inhibited the growth and activity of RANKL-induced osteoclasts in vitro in a dose-dependent manner, and Elt exerted no cell-killing effect within the effective inhibitory concentration. Mechanistically, Elt was found to trap IκBα in the nucleus and thus protect IκBα from proteasome degradation, which resulted in the blocking of the translocation of IκBα and NF-κB p65 and the consequent inhibition of NF-κB activity. The suppression of NF-κB activity, in turn, inhibited the activity of two transcription factors (NFATc1 and c-Fos) essential for osteoclast formation and led to the downregulation of genes and proteins related to bone resorption. Our study thus provides a newly identified mechanism for targeting in the treatment of osteoporosis.

Psoriasis is an autoimmune skin disorder influenced by genetic, epigenetic and environmental factors. We previously found CYP2S1 intragenic DNA methylation cg19430423 site strongly hypomethylated in psoriatic skin tissues. In this study, we performed methylation loci fine-mapping to search the top signals in the entire CYP2S1 gene region, and further carried out gene expression assay, cell proliferation, apoptosis, differentiation and migration in CYP2S1 overexpressed (CYP2S1over) and silenced (siRNA) human keratinocytes. Target bisulphite conversion sequencing revealed cg19430423 and nearby two loci were the top differentially methylated loci. These three loci located within active enhancer region marked by H3K4Me1 and H3K27AC peaks. Cg19430423 might not bind with ATF1 directly. CYP2S1over repressed NHEK cell proliferation, but have no confirmed evidence on affecting migration, apoptosis and differentiation. Real-time PCR showed that CYP2S1 inhibited expression of IL1β, IL8, IL33, IL36, LL37, CXCL10 and CCL20 gene. In summary, CYP2S1 might inhibit keratinocyte proliferation, and modulate immune response through IL-8, IL-33, IL-36, CXCL-10, CCL20, thus contribute to the development of psoriasis.

Abstract Background CD74-ROS1 fusion genes have been detected in non-small cell lung carcinomas (NSCLC), but not in inflammatory breast cancer. Case presentation Herein, we report a CD74-ROS1 fusion gene identified in a 64-year-old Chinese woman with inflammatory breast cancer (IBC). The patient initially presented with a rapidly growing mass in the left breast with diffuse erythema developing over a period of 2 months. Diagnosis of invasive breast carcinoma was made by core needle biopsy. Positron emission tomography-computed tomography (PET/CT) demonstrated multiple organ metastases. Genomic DNA was extracted from tumor tissue and analyzed using next-generation sequencing (NGS). The CD74-ROS1 fusion gene was detected in the genomic DNA. The patient refused crizotinib treatment, and could not tolerate the side effects of palliative chemotherapy. Unfortunately, the patient died 4 months after diagnosis. Conclusion We report the case of a CD74-ROS1 fusion gene in a patient with IBC. This may reveal, for the first time, a possible association between CD74-ROS1 gene fusion and rapid progression of inflammatory breast cancer. Multigene panel testing can be performed when rapidly progressive breast cancer occurs and could reveal potential therapeutic strategies.

BackgroundPatients with cancer experience multiple symptoms related to cancer, cancer treatment, and the procedures involved in cancer care; however, many patients with pain, depression, and fatigue, especially those outside the hospital, receive inadequate treatment for their symptoms. Using an electronic patient-reported outcome (ePRO) platform to conduct symptom management follow-up in outpatients with advanced cancer could be a novel and potentially effective approach. However, empirical evidence describing in detail the preparation and implementation courses in a real setting is needed. ObjectiveThe purpose of this paper was to describe the implementation process and evaluation of an ePRO platform that facilitates symptom management for patients with cancer, share our experiences and the problems we encountered during the process of implementation, and share the solutions we identified for those problems. Moreover, we tested the feasibility, safety, and efficacy of the ePRO platform. MethodsThis was a real-world, ongoing, longitudinal, single-center, prospective study with a total of 7 follow-ups conducted within 4 weeks after the first visit to the symptom management clinic (on days 1, 3, 7, 10, 14, 21, and 28). Participants were encouraged to complete scales for physical symptoms (pain, fatigue, and shortness of breath), cognitive symptoms (memory problems and impaired concentration), and affective symptoms (especially depression and anxiety) during follow-up. The design and function of the ePRO-doctor client and ePRO-patient client, the patient-reported outcome (PRO) scales used in the study, and the strategies to promote symptom tracking have been described. Moreover, the training and evaluation for research assistants have been presented. The efficacy of the ePRO platform was assessed with a comparison of the baseline and 4-week outcomes on the MD Anderson Symptom Inventory. ResultsUsing the ePRO platform for symptom management follow-ups in advanced cancer patients was associated with a high completion rate (72.7%-86.4%) and a low drop-off rate (23.6%). The ePRO platform sent 293 alert notifications to both patients and doctors, which promoted patient security. The short and sharp PRO tool selection, user-friendly interface, automatic reminder notifications and alerts, and multiple dimensional training were essential components for the preparation and implementation of the ePRO system. The results showed significant improvements in the mean scores of pain, fatigue, and numbness from baseline to day 28 (P=.02, P=.02, and P

PURPOSEThe purpose of this study was to describe follow-up care for breast and colorectal cancer survivors in countries with varying levels of resources and highlight challenges regarding posttreatment survivorship care.METHODSWe surveyed one key stakeholder from each of 27 countries with expertise in survivorship care on questions including the components/structure of follow-up care, delivery of treatment summaries and survivorship care plans, and involvement of primary care in survivorship. Descriptive analyses were performed to characterize results across countries and variations between the WHO income categories (low, middle, high). We also performed a qualitative content analysis of narratives related to survivorship care challenges to identify major themes.RESULTSSeven low- or /lower-middle-income countries (LIC/LMIC), seven upper-middle-income countries (UMIC), and 13 high-income countries (HICs) were included in this study. Results indicate that 44.4% of countries with a National Cancer Control Plan currently address survivorship care. Additional findings indicate that HICs use guidelines more often than those in LICs/LMICs and UMICs. There was great variation among countries regardless of income level. Common challenges include issues with workforce, communication and care coordination, distance/transportation issues, psychosocial support, and lack of focus on follow-up care.CONCLUSIONThis information can guide researchers, providers, and policy makers in efforts to improve the quality of survivorship care on a national and global basis. As the number of cancer survivors increases globally, countries will need to prioritize their long-term needs. Future efforts should focus on efforts to bridge oncology and primary care, building international partnerships, and implementation of guidelines.

Abstract Background Temperature is known to affect living organisms and alter the expression of responsive genes, which affects a series of life processes, such as development, reproduction and metabolism. Several genes and gene families have been involved in high temperature responses, such as heat shock protein (hsp) family, Jumonji family and genes related to cortisol synthesis. Gonad is a vital organ related to the existence of a species. However, the comprehensive understanding of gonadal responses to environmental temperature is limited. Results To explore the effects of environmental temperature on genes and gene networks in gonads, we performed acute heat treatment (48 h) on Chinese tongue sole (Cynoglossus semilaevis). Gonadal transcriptome analysis was conducted on females, pseudomales and males exposed to high (28 °C) and normal (22 °C) temperatures. A total of 1226.24 million clean reads were obtained from 18 libraries. Principal component analysis (PCA) and differentially expressed gene (DEG) analysis revealed different performance of sex responses to heat stress. There were 4565, 790 and 1117 specific genes altered their expression level in females, pseudomales and males, respectively. Of these, genes related to hsp gene family, cortisol synthesis and metabolism and epigenetic regulation were involved in early heat response. Furthermore, a total of 1048 DEGs were shared among females, pesudomales and males, which may represent the inherent difference between high and normal temperatures. Genes, such as eef1akmt3, eef1akmt4, pnmt and hsp family members, were found. Conclusions Our results depicted for the first time the gonadal gene expression under acute high temperature treatment in Chinese tongue sole. The findings may provide a clue for understanding the responses of genes and networks to environmental temperature.

Abstract Straw return is an effective strategy to alleviate soil-borne diseases. Though watermelon Fusarium wilt is a severe soil-borne disease, the effect of wheat straw on the disease remains unclear. Thus, we investigated the effects of wheat straw on soil bacterial and fungal communities by adding wheat straw to consecutive watermelon soil in the greenhouse condition. The microbiome changes were further investigated using network analysis based on 16S rDNA and internal transcribed spacer deep sequencing. Wheat straw addition increased the fungal community diversity, whereas the bacterial diversity was not affected. Compared to the control group, the relative abundance of some bacteria, including Actinobacteria, Chloroflexi, and Saccharibacteria, was increased with wheat straw addition. For fungi, the relative abundance of Fusarium was decreased with wheat straw addition. Microbial network analysis demonstrated that the fungal community has a more complex connection than the bacterial community. In addition, redundancy analysis indicated that the Fusarium genera were significantly related to the disease index. Taken together, the addition of wheat straw might affect the microbial community through increasing the relative abundance of phylum Actinobacteria, decreasing the relative abundance of Fusarium, and increasing the fungal network complexity to enhance the defense of watermelon against Fusarium wilt disease.

ObjectiveThe present study aimed to prospectively evaluate the role of metagenomic next-generation sequencing (mNGS) in the etiological diagnosis of patients with perioperative infective endocarditis (IE).MethodsFrom May 1st, 2019 to December 31st, 2020, a total of 99 patients with IE were enrolled in the present study according to the modified Duke criteria, etiological, and pathological results. 11 non-IE patients undergoing heart valve surgery in the same period were selected as the control group. A blood culture test was performed immediately after admission, and the valves harvested operatively were examined by blood culture and mNGS.ResultsIn the IE group, there were 29 cases (29.3%) with positive blood culture, 16 cases (16.2%) with positive valve culture, and 85 cases (85.9%) with positive valve mNGS. Compared to culture-based detection, mNGS achieved better performance with a sensitivity, specificity, area under the curve (AUC) of 0.859, 0.727, and 0.793, respectively. The combined approach using culture and mNGS further improved the diagnostic accuracy (sensitivity 89.9%, specificity 72.7%, AUC 0.813). Preoperative white blood cell (P = 0.029) and neutrophils (P = 0.046) were identified as independent factors affecting the detection rate of mNGS. In the mNGS-positive group, 95 strains of pathogens were found and 10 cases were identified with mixed infection. There were 72 gram-positive bacteria and 14 gram-negative bacteria. mNGS positive group displayed higher species richness than mNGS negative group with enrichment of Streptococcus sanguis, Streptococcus buccalis, and Streptococcus griseus. Proteobacteria and Actinomycetes were enriched in mNGS negative group. Notably, six patients showed disconcordant results between culture and mNGS. Rothia aeria was identified in the blood culture, valve culture, and valve mNGS in one patient. Bartonella Quintana and Coxiella burnetii, which were fastidious intracellular bacteria, were found in two blood and valve culture-negative cases.ConclusionsmNGS outperformed the conventional culture method and displayed high accuracy in detecting pathogens in IE patients. This study provided support for the use of mNGS in the etiological diagnosis of IE.

The Chanarin–Dorfman syndrome (CDS) is a rare, autosomal recessively inherited genetic disease, whch is associated with a decrease in the lipolysis activity in multiple tissue cells. The clinical phenotype involves multiple organs and systems, including liver, eyes, ears, skeletal muscle and central nervous system. Mutations in ABHD5/CGI58 gene have been confirmed to be associated with CDS. We performed whole exome sequencing on a Chinese CDS patient with skin ichthyosis features mimicking lamellar ichthyosis, ectropion, sensorineural hearing loss, and lipid storage in peripheral blood neutrophils. A novel homozygous missense mutation (p.L154R) in ABHD5 gene was detected in this patient. Genotype-phenotype analysis in reported CDS patients revealed no particular correlation. Our findings further enrich the reservoir of ABHD5 mutations in CDS.

Ferulate 5-hydroxylase (F5H) is a cytochrome P450-dependent monooxygenase that plays a key role in the biosynthesis of syringyl (S) lignin. In this study, mining of flax (Linum usitatissimum) genomic data enabled the identification of nine LuF5H genes. Bioinformatics analysis revealed the physicochemical properties, gene structures, conserved motifs, phylogenetic evolutionary features and promoter cis-acting elements related to these genes and their encoded proteins. Based on the gene structural and phylogenetic features, the nine LuF5Hs were assigned to two subclasses. The expression levels of the nine LuF5Hs was analyzed by the RNA-seq technique, and the RNA-seq data were verified by qRT-PCR. The results of the RNA-seq analysis showed that LuF5H genes belonging to the same subclass exhibited similar expression patterns. Notably, the transcripts of the LuF5H3 and LuF5H7 subclass 1 genes accumulated at high levels in stem tissues, thus indicating that LuF5H3 and LuF5H7 are the main LuF5H genes involved in flax lignin biosynthesis. Furthermore, the expression levels of LuF5H1, LuF5H3, LuF5H4 and LuF5H7 were upregulated 1.2–1.9-fold under drought, NaCl stress and brassinosteroid treatment conditions. This first comprehensive study of the flax F5H gene family provides valuable data for use in gene function analysis toward improving flax fiber quality and reducing flax manufacturing costs and associated environmental pollution.

Tim-3, an immune checkpoint inhibitor, is widely expressed on the immune cells and contributes to immune tolerance. However, the mechanisms by which Tim-3 induces immune tolerance remain to be determined. Major histocompatibility complex II (MHC-II) plays a key role in antigen presentation and CD4+T cell activation. Dysregulated expressions of Tim-3 and MHC-II are associated with the pathogenesis of many autoimmune diseases including multiple sclerosis. Here we demonstrated that, by suppressing MHC-II expression in macrophages via the STAT1/CIITA pathway, Tim-3 inhibits MHC-II-mediated autoantigen presentation and CD4+T cell activation. As a result, overexpression or blockade of Tim-3 signaling in mice with experimental autoimmune encephalomyelitis (EAE) inhibited or increased MHC-II expression respectively and finally altered clinical outcomes. We thus identified a new mechanism by which Tim-3 induces immune tolerance in vivo and regulating the Tim-3-MHC-II signaling pathway is expected to provide a new solution for multiple sclerosis treatment.

The outbreak and persistence of COVID-19 have posed a great threat to global public health and economic development. The continuous economic deterioration has been intensified due to the continuous prevention and control measures, such as closed management. Insisting on the prevention of the epidemic or economic restart has become a dilemma for all countries. Epidemic prevention is not only the main behavior of a single country but also a common problem faced by all countries in the region. Continuous prevention measures will affect economic development, but an early restart of the economy is faced with the recurrence of the epidemic. To avoid the emergence of prisoner's dilemma in the governance of the epidemic, each country cannot make decisions with its optimization, and so it is necessary to build a regional cooperation mechanism to achieve the overall optimization of the economy and prevent the epidemic. Based on the game theory, we analyzed the behavior of countries when carrying out regional cooperation to govern the epidemic and put forward specific cooperative income distribution schemes according to the different attributes of the countries. Our results showed that in the presence of population mobility, regional cooperation to govern the epidemic can minimize the total number of infected people and maximize the overall utility of the region, which was significantly better than the overall benefits of the region in the case of non-cooperation. However, in detail, the smaller the difference of preference for preventing and controlling the epidemic between the two, the more likely it is to lead to a win-win situation. Otherwise, there will be one with damaged interests. When damaged interests appear, the appropriate distribution of cooperative income to the country with a small economic scale and low preference in preventing the epidemic is more conducive to the achievement of cooperative mechanisms and the realization of a win-win situation in the region.