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Objective: Illumination of the integrative effects of herbs in a formula is a bottleneck that limits the development of traditional Chinese medicine (TCM). In the present study, we developed a transcriptome-based multi-scale network pharmacology model to explore the combined effects of different herbs. Materials and Methods: First, we curated gene signatures at different biological scales, from the molecular to higher tissue levels, including tissues, cells, pathological processes, biological processes, pathways, and targets. Second, using the Xiexin Tang (XXT) formula as an example, we collected transcriptomic data in response to the treatment of XXT or its three compositive herbs on Michigan cancer foundation7 cells. Third, we linked each herbal drug to different biological scales by calculating the correlation scores between herb-induced gene expression profiles and gene signatures. Finally, the combined mechanisms of the three constituent herbs in XXT were deciphered by comparing their multi-scale effects with those of the formula. Results: The results showed that although XXT or single herbs regulated a large number of signatures on each biological scale, the phenotypic effects of these herbal drugs are concentrated onto the “Blood” tissue, types of hemocytes, and hemorrhagic injury-related pathological processes. At the molecular level, these herbs consistently regulate processes such as the cell cycle and blood coagulation-related pathways, as well as protein targets related to the immunoinflammatory response and blood coagulation, such as proteinase-activated receptor 2, integrin beta-3, inhibitor of nuclear factor kappa-B kinase subunit beta, and coagulation factor XII. The analysis of the combinational modes demonstrated that different herbs can cooperate by acting on the same objects and/or regulating different objects in related functions, and cooperative behaviors change at different biological scales. Conclusions: Our model can dissect the combined effects of herbal formulae from a multi-scale perspective and should be beneficial for the development and exploitation of TCM.

Abstract Background Cancer susceptibility germline mutations are associated with pancreatic ductal adenocarcinoma (PDAC). However, the hereditary status of PDAC and its impact on survival is largely unknown in the Asian population. Methods Exome sequencing was performed on 527 blood samples from PDAC individuals and analyzed for mutations in 80 oncogenic genes. Pathogenic and likely pathogenic (P/LP) germline variants were diagnosed according to the ACMG variant classification categories. The association between germline homologous recombination gene mutations (gHR mut , including BAP1, BRCA1, BRCA2, PALB2, ATM, BLM, BRIP1, CHEK2, NBN, MUTYH, FANCA and FANCC) and the treatment outcomes was explored in patients with stage III/IV diseases treated with first-line (1L) platinum-based versus platinum-free chemotherapy. Results Overall, 104 of 527 (19.7%) patients carried germline P/LP variants. The most common mutated genes were BRCA2 (3.60%), followed by ATR (2.66%) and ATM (1.9%). After a median follow-up duration of 38.3-months (95% confidence interval, 95% CI 35.0–43.7), the median overall survival (OS) was not significantly different among patients with gHR mut , non-HR germline mutations, or no mutation (P = 0.43). Among the 320 patients with stage III/IV disease who received 1L combination chemotherapy, 32 (10%) had gHR mut . Of them, patients receiving 1L platinum-based chemotherapy exhibited a significantly longer median OS compared to those with platinum-free chemotherapy, 26.1 months (95% CI 12.7–33.7) versus 9.6 months (95% CI 5.9–17.6), P = 0.001. However, the median OS of patients without gHR mut was 14.5 months (95% CI 13.2–16.9) and 12.6 months (95% CI 10.8–14.7) for patients receiving 1L platinum-based and platinum-free chemotherapy, respectively (P = 0.22). These results were consistent after adjusting for potential confounding factors including age, tumor stage, performance status, and baseline CA 19.9 in the multivariate Cox regression analysis. Conclusions Our study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHR mut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis.

To handle imbalanced datasets in machine learning or deep learning models, some studies suggest sampling techniques to generate virtual examples of minority classes to improve the models' prediction accuracy. However, for kernel-based support vector machines (SVM), some sampling methods suggest generating synthetic examples in an original data space rather than in a high-dimensional feature space. This may be ineffective in improving SVM classification for imbalanced datasets. To address this problem, we propose a novel hybrid sampling technique termed modified mega-trend-diffusion-extreme learning machine (MMTD-ELM) to effectively move the SVM decision boundary toward a region of the majority class. By this movement, the prediction of SVM for minority class examples can be improved. The proposed method combines α-cut fuzzy number method for screening representative examples of majority class and MMTD method for creating new examples of the minority class. Furthermore, we construct a bagging ELM model to monitor the similarity between new examples and original data. In this paper, four datasets are used to test the efficiency of the proposed MMTD-ELM method in imbalanced data prediction. Additionally, we deployed two SVM models to compare prediction performance of the proposed MMTD-ELM method with three state-of-the-art sampling techniques in terms of geometric mean (G-mean), F-measure (F1), index of balanced accuracy (IBA) and area under curve (AUC) metrics. Furthermore, paired t-test is used to elucidate whether the suggested method has statistically significant differences from the other sampling techniques in terms of the four evaluation metrics. The experimental results demonstrated that the proposed method achieves the best average values in terms of G-mean, F1, IBA and AUC. Overall, the suggested MMTD-ELM method outperforms these sampling methods for imbalanced datasets.

Diaphorina citri Kuwayama (D. citri) is one of the major pests in the citrus industry, which spreads Citrus Huanglongbing disease. It has developed resistance to chemical insecticides. Therefore, searching for greener solutions for pest management is critically important. The main aim of this study was to evaluate the repellent and insecticidal efficacy of essential oils (EOs) from four species of Myrtaceae plants: Psidium guajava (PG), Eucalyptus robusta (ER), Eucalyptus tereticornis (ET), and Baeckea frutescens (BF) against D. citri and to analyze their chemical compositions. GC-MS analysis was performed, and the results indicated that the EOs of PG, ER, ET, and BF were rich in terpenoids, ketones, esters, and alcohol compounds. The repellent rate of all four EOs showed that it decreased with exposure time but increased with the concentration of EOs from 80.50% to 100.00% after treating D. citri for 6 h with four EOs at 100% concentration and decreased to 67.71% to 85.49% after 24 h of exposure. Among the compounds from the EOs tested, eucalyptol had the strongest repellent activity, with a 24 h repellency rate of 100%. The contact toxicity bioassay results showed that all EOs have insecticidal toxicity to D. citri; the LC50 for nymphs was 36.47–93.15 mL/L, and for adults, it was 60.72–111.00 mL/L. These results show that when PG is used as the reference material, the ER, ET, and BF EOs have strong biological activity against D. citri, which provides a scientific basis for the further development of plant-derived agrochemicals.

Abstract Background Citrus fruits are economically and nutritionally important but have been severely affected by Huanglongbing disease (HLB), its natural spread is mainly by the Asian Citrus Psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae). Chemicals are often used to control this pest, but this is not sustainable. Meanwhile, there are few environmentally friendly bioinsecticides to control D. citri in China. Results In this study, an entomofungal pathogen wz-1 was isolated from a D. citri carcass in the field, which resulted in a cumulative mortality rate of 75.27% in adult D. citri 7 days after inoculation of the spore suspension. It was identified as Cladosporium subuliforme based on morphological analysis as well as sequence analysis of several molecular markers (Internal Transcribed Spacers, Translation Elongation Factor 1-α and Actin). Remarkably, the lethality rate of adult D. citri reached 53.13%, 48 h after treatment with the aqueous phase extracts of wz-1. Hydroxyquinoline and phytosphingosine in the extracts were identified as potentially active metabolites using LC–MS. Conclusions The entomopathogenicity and bioinsecticidal potential of C. subuliforme were previously unknown. Obtained results showed that both spores and extracts of wz-1 can effectively kill adult D. citri, providing an available fungal resource and a theoretical basis for biocontrol of the HLB insect vector D. citri.

Abstract Background Previous studies have shown that monotherapy with apatinib, an oral tyrosine kinase inhibitor, has promising efficacy for treating recurrent or metastatic (RM) nasopharyngeal carcinoma (NPC) patients. In this study, we aimed to assess the efficacy and safety of apatinib combined with capecitabine as a second-line therapy or beyond for treating RM-NPC patients who failed the first-line platinum-based chemotherapy. Methods In this single-arm, phase II study, we enrolled RM-NPC patients who had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The sample size was determined using Simon’s two-stage design. All patients were administered with apatinib 500 mg once daily and capecitabine 1000 mg/m2 twice per day on days 1–14 of each 21-day cycle. The primary endpoint was the objective response rate (ORR), and the secondary endpoints comprised disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results We enrolled 64 patients from September 2018 to August 2020. The ORR and DCR were 39.1% (95% CI, 27.1–52.1) and 85.9% (95% CI, 75.0–93.4), respectively. The median DoR was 14.4 months (95% CI, 7.8–21.0). As of April 20, 2021, the median follow-up duration was 12.0 months. The median PFS was 7.5 months (95% CI, 5.0–10.0) and the median OS was 15.7 months (95% CI, 11.3–20.1). The most common toxicities of any grade were anemia (75.0%), hand-foot syndrome (65.6%), and proteinuria (64.0%). Grade 3–4 toxicities were observed in 36 (56.3%) patients, with hypertension (14.1%), mucositis (12.4%), and fatigue (10.9%) most commonly observed. Conclusions Apatinib plus capecitabine shows promising efficacy as a second-line treatment option in pretreated platinum-refractory RM-NPC patients. Dose selection of this combination needs further investigation considering the toxicity. Trial registration Chi-CTR1800017229.

Objectives: Overt and occult hepatitis B infection (HBI) among mothers and infants were investigated, and the effectiveness of vaccination against HBI was evaluated based on transmission types. Methods: A hospital-based cohort was built with 2,734 mothers and 330 mother-infant pairs. Their demographic data were collected. Serological HBV markers, nested-PCR for HBV genes, viral load detection, and phylogenetic analysis were done. Results: The overall prevalence of HBI among mothers was 12.1% (330/2,734), with 10.4% for the overt type and 1.8% for the occult type. In 330 out of 1,650 (20%) mother-infant pairs, the overall, type-I (from overt mother to overt infant), type-II (from overt mother to occult infant), and type-Ⅲ (from occult mother to occult infant) transmissions were 1.9% (1/54), 5.6% (3/54) and 0.0% (0/7). The refinement of HBI classification improved the estimate of vaccine effectiveness against HBI from 74.4%–80.9% to 94.4%, which was more prominent for type-II. One mother-infant pair with type-II transmission shared nearly identical complete sequences. However, the high rate of lost-to-follow-up could not be ignored. Conclusions: During the transition period, HBV is mainly transmitted from the overt type of HBI mother to infant. Intensive prenatal screening for mothers is vital.

Sugarcane is a cash crop that plays an integral part in the sugar industry. The Sustainable Sugarcane Initiative (SSI) has been adopted globally, ensuring enough and aiming for more yield, helping increase disease-free sugarcane cultivation. Single-bud seeds could be the best approach for sugarcane cultivation. Indole-3-butyric acid (IBA) is a rooting agent utilized significantly in seedling propagation. Greenhouse experiment results discovered the significant growth promotion in sugarcane seedlings and accumulation of plant hormones at 100 ppm IBA. Next, we performed transcriptomic analysis of sugarcane buds using RNA sequencing and compared their gene expression during root development due to affect of IBA (100 ppm). A total of 113,475 unigenes were annotated with an average length of 836 bp (N50 = 1,536). The comparative RNA-seq study between the control (CK) and IBA-treated (T) buds showed significant differentially expressed unigenes (494 upregulated and 2086 downregulated). The IBA influenced major biological processes including metabolic process, the cellular process, and single-organism process. For cellular component category, cell, cell part, organelle, membrane, and organelle part were mainly affected. In addition, catalytic activity and binding were primarily affected in the molecular function categories. Furthermore, the expression of genes related to plant hormones and signaling pathways was analyzed by qRT-PCR, which was consistent with the RNA-seq expression profile. This study provides new insights into the IBA response to the bud sprouting in sugarcane based on RNA sequencing, and generated information could help further research on breeding improvement of sugarcane.

Knowledge about the influence of host genetics on the vaginal bacteriome in pregnancy is still limited. Although a number of environmental and behavioral factors may exert influences on the structure of vaginal bacterial communities, the vaginal bacteriome often undergoes a relatively fixed transition to a more stable and less diverse state as the menstrual cycle stops, which raises questions on the effects of human genetics.

Hexabromocyclododecane (HBCD) is one of the most frequently used brominated flame retardants (BFRs) in the industries nowadays. Despite being listed as persistent organic pollutant (POP), it is still in use until 2025. Because of its bio-accumulative and toxic characteristics, the applicable remediation approach is required. The aim of this study is to identify the microbial community from soil with HBCD degradation ability. The soil suspension and soil samples from Chiang Chun Soil and River Bank Soil showed to degrade HBCD by 60% 4 days after treatment, the debromination ratio was around 60%, and the total HBCD removal ratio reached 70% and 77.9%, respectively. The HBCD debromination metabolites, and oxidation metabolites were identified by GC–MS. The microbial taxonomic diversity was observed with DGGE approach to evaluate the effect of HBCD of microbial community. Bacillus spp. and Clostridium spp. were identified as the dominant microbes in the Chiang Chun Soil, but the amount of Bacillus spp. were showed to be affected by HBCD. In conclusion, HBCD could be removed by the microbial consortium in soil under aerobic culturing condition by various metabolic pathways.

Abstract In this paper, the color-octet long distance matrix elements are studied through the inclusive $$J/\psi $$ J / ψ production in $$e^{+}e^{-}$$ e + e - annihilation within the framework of non-relativistic QCD factorization. The calculations are up-to next-to-leading order with the radiative and relativistic corrections in the energy region of the B-factory and the near-threshold region of $$4.6{-}5.6~\mathrm{GeV}$$ 4.6 - 5.6 GeV . A constraint of the long distance matrix elements ( $$\langle ^1S_0^{8}\rangle $$ ⟨ 1 S 0 8 ⟩ , $$\langle ^3P_0^{8}\rangle $$ ⟨ 3 P 0 8 ⟩ ) is obtained. Through our estimation, the P-wave color-octet matrix element $$(\langle 0|^3P^8_0|0\rangle )$$ ( ⟨ 0 | 3 P 0 8 | 0 ⟩ ) should be of the order of $$0.008m_\mathrm{c}^2~\mathrm{GeV}^3$$ 0.008 m c 2 GeV 3 or less. The constrained region is not compatible with the values of the long distance matrix elements fitted at hadron colliders.

Background: Acupressure has been widely used for quitting smoking for a long time in China. This study explores the feasibility and effects of acupressure on smoking cessation in young smokers with nicotine dependence to inform policy and decision-making. Methods: This was a single group study using pre/post-test design. Participants received four weeks of auricular acupressure treatment, led by a registered acupuncturist. Smoking cravings, nicotine dependence, withdrawal symptoms, and cigarettes per day (CPD) were recorded before and after treatment. Changes in outcomes were analyzed at 2 weeks and 4 weeks using SPSS software version 22.0. Semi-structured interviews were conducted with participants to explore their experience and attitude towards auricular acupressure. Thematic analysis was applied to analyze the data. Results: A total of 20 participants completed this study. A significant reduction was observed in smoking cravings (F = 11.02, P < 0.05), nicotine dependence (F = 11.09, P < 0.05), withdrawal symptoms (F = 11.19, P < 0.05), and CPD (F = 19.03, P < 0.05) over sessions. Additionally, withdrawal symptoms decreased significantly from 2 weeks to 4 weeks (P < 0.05) of acupressure treatment. Three inter-related themes emerged from interviews: personal and external resources, psychological and physical effects of acupressure, and satisfaction with acupressure for smoking cessation. Conclusion: The quantitative and qualitative data suggest that acupressure maybe effective in decreasing nicotine dependence and smoking cravings. However, this was a pilot and single arm study, these effects need to be further verified. The study supports the feasibility and safety of introducing acupressure therapy for smoking cessation in young smokers.

Background: This study aimed to understand the longitudinal relationship between psychosocial stress with tic exacerbation in children with Tourette syndrome (TS) and chronic tic disorder. Methods: Consecutive ratings of tic severity as well as child and parental reports of psychosocial stress were obtained for 373 children (296 males, 77 females; mean age 9y 5mo; SD 3y 3mo) with TS and chronic tic disorder between January 2018 and December 2020. The Yale Global Tic Severity Scale (YGTSS) global severity score, total tic score, and impairment rating were calculated. The stressful events and YGTSS measurements were used and treated as time-varying variables in the analyses. Models that controlled for non-independence among the repeated observations using a random intercept and random slope model were employed. Each participant was treated as a random factor in the modelling. Results: Family-related stress, personal relationship stress and school-related stress were independently associated with increasing YGTSS global severity, total tic score, and impairment rating over time. An increased number of stressful events were associated with increased severity of tics. Conclusion: Family, personal relationships, and school-related stress were consistently associated with the exacerbation of tics. Managing these stressful events is important in the treatment of TS and chronic tic disorder.

Introduction Acupuncture and related acupoint therapies have been widely used for smoking cessation. Some relevant systematic reviews (SRs) have been published. There is a need to summarize and update the evidence to inform practice and decision-making. Methods Eight databases were searched from their inception to December 2023. SRs, any randomized controlled trials (RCTs) comparing acupuncture therapies with sham acupuncture, pharmacotherapy, behavioral therapy, or no treatment, were included. The primary outcome was the abstinence rate. AMSTAR-2 was employed to assess the quality of SRs. An updated meta-analysis was conducted based on SRs and RCTs. Data were synthesized using risk ratios (RR) with 95% confidence intervals (CIs). The GRADE approach was employed to assess the certainty of the updated evidence. Results Thirteen SRs and 20 RCTs outside of the SRs were identified. The SRs were of low or very low quality by AMSTAR-2. Sixteen (80%) RCTs were at high risk of performance bias. Eight acupuncture and related acupoint therapies were involved. The short-term (≤6 months) abstinence rate outcome was summarized as follows. Most SRs suggested that filiform needle acupuncture or acupressure had a better effect than sham acupuncture, but the findings were inconsistent. The updated meta-analysis also suggested that filiform needle acupuncture was more effective than sham acupuncture (RR=1.44; 95% CI: 1.02–2.02; I 2 = 66%; low certainty; 9 RCTs, n=1358). Filiform needle acupuncture combined with acupressure was comparable to nicotine patches (RR=0.99; 95% CI: 0.74–1.32; low certainty; 6 RCTs, n= 524). Acupressure was superior to counseling (RR=1.46; 95% CI: 1.14–1.87; I 2 =5%; low certainty; 8 RCTs, n=595). No serious adverse events were reported in these SRs or RCTs. Conclusions Low certainty evidence suggests that filiform needle acupuncture and auricular acupressure appear to be safe and effective in achieving short-term smoking cessation. However, long-term follow-up data are needed.

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As a cost-effective method, electrodeposition has been widely applied to synthesize materials for the fabrication of micro thermoelectric devices. However, it is hard to obtain smooth, compact and high-performance p-type BiSbTe films when the thickness becomes higher. In this work, multiple additives consist of PVA and saccharin sodium are firstly introduced into the electrolyte bath with the assistance of KCl for electrodeposition. The influence of different additives on reduction kinetics, morphology, stoichiometry and crystalline structure has been thoroughly explored. Besides the electrolyte concentration and the deposition potential, the pulse duration for pulsed deposition also significantly affects the stoichiometry. The smooth, compact and well-adherent films with ideal composition were successfully deposited for the thickness range from 4 to 100 μm. Crystallite size was much refined, and lattice strain slightly increased with the cooperative reaction of multiple additives. The measured Seebeck coefficient reached around 262 ± 25 μV K-1for the deposited film with multiple additives, while that of the film with absence of additives was about 156 ± 14 μV K-1. The electric resistivity increased from 66 μΩ·m to 150 μΩ·m when PVA and saccharin sodium were introduced, but decreased to 81 μΩ·m after increasing the electrolyte conductivity through adding KCl. [ABSTRACT FROM AUTHOR]

Additive manufacturing technology or three-dimensional (3D) printing has been applied in many manufacture fields. The combination of 3D printing and conventional energetic material fields can create sufficient space for preparing and molding of energetic materials. Although recent advances in this field are encouraging, with the printing technologies offering many merits over the traditional fabrication technologies, some application principles and material considerations should be discussed. This review summarizes some of the significant advances in this evolving field over the past few years, lists the typical application cases, discusses the current challenge, and presents the possible future development trend.