Alterations in the brain functional network of abstinent male individuals with methamphetamine use disorder.

Methamphetamine is a highly addictive psychostimulant drug that is abused globally and is a serious threat to health worldwide. Unfortunately, the specific mechanism underlying addiction remains unclear. Thus, this study aimed to investigate the characteristics of functional connectivity in the brain network and the factors influencing methamphetamine use disorder in patients using magnetic resonance imaging. We included 96 abstinent male participants with methamphetamine use disorder and 46 age- and sex-matched healthy controls for magnetic resonance imaging. Compared with healthy controls, participants with methamphetamine use disorder had greater impulsivity, fewer small-world attributes of the resting-state network, more nodal topological attributes in the cerebellum, greater functional connectivity strength within the cerebellum and between the cerebellum and brain, and decreased frontoparietal functional connectivity strength. In addition, after controlling for covariates, the partial correlation analysis showed that small-world properties were significantly associated with methamphetamine use frequency, psychological craving, and impulsivity. Furthermore, we revealed that the small-word attribute significantly mediated the effect of methamphetamine use frequency on motor impulsivity in the methamphetamine use disorder group. These findings may further improve our understanding of the neural mechanism of impulse control dysfunction underlying methamphetamine addiction and assist in exploring the neuropathological mechanism underlying methamphetamine use disorder-related dysfunction and rehabilitation.

Exploring causal correlations between circulating levels of cytokines and colorectal cancer risk: A Mendelian randomization analysis.

Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome-wide association study (GWAS) including 14,824 European-ancestry participants. Summary-level data for colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL-12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00-1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin-12p70 levels (IL-12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13-1.43; p < 1.22 × 10-3). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02-1.35; p = .026), macrophage colony-stimulating factor (M-CSF) (OR: 0.85; 95% CI: 0.76-0.96; p = .005), IL-13 (OR: 1.15; 95% CI: 1.02-1.30; p = .028), IL-10 (OR: 1.23; 95% CI: 1.01-1.49; p = .037), and IL-7 (OR: 1.19; 95% CI: 1.02-1.39; p = .024). Our MR studies support that one cytokine IL-12 is significantly associated with CRC risk and that five cytokines VEGF, M-CSF, IL-13, IL-10, and IL-7 are associated with CRC risk.

Occurrence and Flow Behavior for Oil Transport in Mixed Wetting Nanoscale Shale Bedding Fractures.

Shale reservoirs are characterized by an abundance of nanoscale porosities and microfractures. The states of fluid occurrence and flow behaviors within nanoconfined spaces necessitate novel research approaches, as traditional percolation mathematical models are inadequate for accurately depicting these phenomena. This study takes the Gulong shale reservoir in China as the subject of its research. Initially, the unique mixed wetting characteristics of the Gulong shale reservoir are examined and characterized using actual micropore images. Subsequently, the occurrence and flow behavior of oil within the nanoscale bedding fractures under various wettability scenarios are described through a combination of microscopic pore image and molecular dynamics simulations. Ultimately, a mathematical model is established that depicts the velocity distribution of oil and its apparent permeability. This study findings indicate that when the scale of the shale bedding fractures is less than 100 nm, the impact of the nanoconfinement effect is significant and cannot be overlooked. In this scenario, the state of oil occurrence and its flow behavior are influenced by the initial oil-wet surface area on the mixed wetting walls. The study quantifies the velocity and density distribution of oil in mixed wetting nanoscale shale bedding fractures through a mathematical model, providing a crucial theoretical basis for upscaling from the nanoscale to the macroscale.

Association between maternal HIV status and postpartum depressive symptoms in Botswana.

Few studies have evaluated postpartum depression (PPD) in women living with HIV (WLHIV) in Botswana, a high prevalence HIV setting. The Edinburgh Postnatal Depression Scale (EPDS) was used to evaluate PPD symptoms in WLHIV (n = 300) and women who are HIV-uninfected (n = 131) in the Tshilo Dikotla study, an observational cohort study with a nested randomized trial. The EPDS was administered at 2, 6, and 12 months postpartum. We assessed the association of (1) HIV infection and (2) antiretroviral therapy (ART) with odds of PPD symptoms (EPDS ≥ 10 or thoughts of self-harm) in the first year postpartum using generalized estimating equations. Of WLHIV, 24 (8.00%) had PPD symptoms at one or more follow-up time points, compared to 9 (6.9%) women who were HIV-seronegative. There was no association between HIV status and PPD symptoms (adjusted odds ratio [aOR]:1.69, 95% confidence interval [CI]: 0.73-3.93, p = 0.225); however, WLHIV on efavirenz-based ART regimens had higher odds of experiencing PPD symptoms compared to dolutegravir-based ART (aOR:3.05, 95% CI:1.16-8.03, p = 0.024).

Uptake, translocation, and metabolism of organophosphate esters (OPEs) in plants and health perspective for human: A review.

Plant uptake, accumulation, and transformation of organophosphate esters (OPEs) play vital roles in their geochemical cycles and exposure risks. Here we reviewed the recent research advances in OPEs in plants. The mean OPE concentrations based on dry/wet/lipid weight varied in 4.80-3,620/0.287-26.8/12,000-315,000 ng g-1 in field plants, and generally showed positive correlations with those in plant habitats. OPEs with short-chain substituents and high hydrophilicity, particularly the commonly used chlorinated OPEs, showed dominance in most plant samples, whereas some tree barks, fruits, seeds, and roots demonstrated dominance of hydrophobic OPEs. Both hydrophilic and hydrophobic OPEs can enter plants via root and foliar uptake, and the former pathway is mainly passively mediated by various membrane proteins. After entry, different OPEs undergo diverse subcellular distributions and acropetal/basipetal/intergenerational translocations, depending on their physicochemical properties. Hydrophilic OPEs mainly exist in cell sap and show strong transferability, hydrophobic OPEs demonstrate dominant distributions in cell wall and limited migrations owing to the interception of Casparian strips and cell wall. Additionally, plant species, transpiration capacity, growth stages, commensal microorganisms, and habitats also affect OPE uptake and transfer in plants. OPE metabolites derived from various Phase I transformations and Phase II conjugations are increasingly identified in plants, and hydrolysis and hydroxylation are the most common metabolic processes. The metabolisms and products of OPEs are closely associated with their structures and degradation resistance and plant species. In contrast, plant-derived food consumption contributes considerably to the total dietary intakes of OPEs by human, particularly the cereals, and merits specifical attention. Based on the current research limitations, we proposed the research perspectives regarding OPEs in plants, with the emphases on their behavior and fate in field plants, interactions with plant-related microorganisms, multiple uptake pathways and mechanisms, and comprehensive screening analysis and risk evaluation.

Correlation between PD-1/PD-L1 and RANKL/OPG in chronic apical periodontitis model of Sprague-Dawley rats.

Chronic apical periodontitis (CAP) is characterized by inflammation and destruction of the apical periodontium that is of pulpal origin, appearing as an apical radiolucent area, and does not produce clinical symptoms. Little is known about whether the PD-1/PD-L1 ratio is associated with the balance between RANKL and OPG in CAP. The relationship between PD-1/PD-L1 and RANKL/OPG in CAP is investigated in this study. A CAP rat model was established using Sprague-Dawley rats. The pulp chambers were exposed to the oral cavity to allow bacterial contamination. The apical tissues of the bilateral mandibular first molars were analyzed for histological morphology using hematoxylin and eosin (H&E) staining. Immunohistochemistry and qRT-PCR were used to determine the expression of PD-1, PD-L1, OPG, and RANKL mRNA and proteins in periapical tissues and mandibular samples, respectively. The radiological images indicated a poorly defined low-density shadow and alveolar bone resorption after periodontitis induction. Histological analysis revealed an infiltration of inflammatory cells and alveolar bone resorption in the periapical tissues. Mandibular mRNA and periapical protein expression of PD-1, PD-L1, and RANKL was upregulated 7-28 days after periodontitis induction, while the expression of OPG was downregulated. No significant relationship was observed between PD-1/PD-L1 and RANKL/OPG at either mRNA or protein levels in CAP. There is an increased expression of PD-1, PD-L1, and RANKL and a decreased expression of OPG, indicating progression of CAP.

Wall-associated kinase-like gene RL1 contributes to red leaves in sorghum.

Red leaves are common in trees but rare in cereal crops. Red leaves can be used as raw materials for anthocyanin extraction and may have some adaptive significance for plants. In this study, we discovered a red leaf phenotype in the F1 hybrids derived from a cross between two sorghum accessions with green leaf. Histological analysis of red leaves and green leaves showed that red compounds accumulate in mesophyll cells and gradually spreads to the entire leaf blade. In addition, we found chloroplasts degraded more quickly in red leaves than in green leaves based on transmission electron microscopy. Metabolic analysis revealed that flavonoids including six anthocyanins are more abundant in red leaves. Moreover, transcriptome analysis revealed that expression of flavonoid biosynthesis genes was upregulated in red leaves. These observations indicate that flavonoids and anthocyanins in particular, are ideal candidates for the red compounds accumulating in red leaves. Segregation analysis of the red leaf phenotype suggested a genetic architecture consisting of three dominant genes, one (RL1 for RED LEAF1) of which we mapped to a 55-kb region on chromosome 7 containing seven genes. Sequencing, reverse transcription-polymerase chain reaction, and transcriptome analysis suggested Sobic.007G214300, encoding a wall-associated kinase, as the most likely candidate for RL1. Fine mapping the red leaf gene and identifying the metabolites that cause red leaf in sorghum provide us with a better understanding of the red leaf phenotype in the natural population of sorghum.

0.1% Nano-silver mediates PD-1/PD-L1 pathway and alleviates chronic apical periodontitis in rats.

This study was to investigate whether the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) and T-helper 17 (Th17)/regulatory T (Treg) balance are associated with chronic apical periodontitis (CAP) relived by 0.1% nano-silver. CAP rat models were established by opening the first molars of the right and left mandible and exposing the pulp cavity to the oral cavity. CAP model was verified by cone-beam computed tomography, X-ray digital radiovisiography, and hematoxylin-eosin (H and E) staining. The rats were randomly divided into the sham, Ca(OH)2, and 0.1% nano-silver groups (n = 12 in each group) 2 weeks after surgery. The pathological changes in the apical area were detected by H and E staining. PD-1, PD-L1, RORγT, IL-17, and Foxp3 in periapical tissues were detected by qRT-PCR and immunohistochemistry. Th17/Treg and PD-1/PD-L1 were analyzed by flow cytometry. After 7, 14, and 21 days of 0.1% nano-silver treatment, inflammatory cells in the apical region were slightly reduced and inflammatory infiltration was relieved compared with the sham group. RORγT, IL-17, PD-1, and PD-L1 decreased and Foxp3 increased after 7, 14, and 21 days of 0.1% nano-silver treatment compared with the sham group (p < 0.05); however, there were no significant differences with Ca(OH)2 group (p > 0.05). Flow cytometry revealed that 0.1% nano-silver solution decreased Th17/Treg and PD-1/PD-L1 ratio. 0.1% Nano-silver significantly reduced the inflammation of CAP in rats. PD-1/PD-L1 was included in Th17/Treg balance restored by 0.1% nano-silver.

Rationale and design of a prospective, multicenter, phase II clinical trial of safety and efficacy evaluation of long course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorectal excision for locally advanced rectal cancer (NCRT-PD1-LARC trial).

BACKGROUND: Long course radiotherapy plus neoadjuvant chemotherapy followed by resection (total mesorectal excision, TME) has accepted widespread recognized in the treatment of locally advanced rectal cancer (LARC). Tislelizumab, an anti-PD1 humanized IgG4 monoclonal antibody, has been demonstrated with clinical activity and is approved for treating recurrent/refractory classical Hodgkin lymphoma and locally advanced/metastatic urothelial carcinoma in China. However, the safety and efficacy of long course (neoadjuvant chemoradiotherapy, NCRT) plus tislelizumab followed by TME for LARC is still uncertain. METHODS: This NCRT-PD1-LARC trial will be a prospective, multicenter and phase II clinical trial designed to evaluate the safety and efficacy of LARC patients treated with long course NCRT plus tislelizumab followed by TME. This trial will consecutively enroll 50 stage II/III LARC patients (cT3N0M0 and cT1-3N1-2M0) with the tumor distal location ≤ 7 cm from anal verge at 7 centers in China. The enrolled patients will receive long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by TME 6-8 weeks after the end of radiotherapy. The primary efficacy endpoint will be the pathological complete response (pCR) rate, which is defined as absence of viable tumor cells in the primary tumor and lymph nodes. DISCUSSION: To our knowledge, this trial is the first multicenter clinical trial in China to assess the safety and efficacy of NCRT plus anti-PD1 therapy followed by TME to treat patients with LARC. NCRT followed by TME was recognized as the most recommended treatment against LARC while could not be completely satisfied in clinic. This study expects to provide a solid basis and encouraging outcomes for this promising combination of radiotherapy, chemotherapy and immunotherapy in LARC. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04911517. Date of registration: 23 May 2021. URL of trial registry record: https://www. CLINICALTRIALS: gov/ct2/show/NCT04911517?id=BFH-NCRTPD&draw=2&rank=1 .

Hybrids of small CD4 mimics and gp41-related peptides as dual-target HIV entry inhibitors.

Hybrid molecules containing small CD4 mimics and gp41-C-terminal heptad repeat (CHR)-related peptides have been developed. A YIR-821 derivative was adopted as a CD4 mimic, which inhibits the interaction of gp120 with CD4. SC-peptides, SC34 and SC22EK, were also used as CHR-related peptides, which inhibit the interaction between the N-terminal heptad repeat (NHR) and CHR and thereby membrane fusion. Therefore, these hybrid molecules have dual-targets of gp120 and gp41. In the synthesis of the hybrid molecules of CD4 mimic-SC-peptides with different lengths of linkers, two conjugating methods, Cu-catalyzed azide-alkyne cycloaddition and direct cysteine alkylation, were performed. The latter reaction caused simpler operation procedures and higher synthetic yields than the former. The synthesized hybrid molecules of CD4 mimic-SC22EK have significantly higher anti-HIV activity than each sole agent. The present data should be useful in the future design of anti-HIV agents as dual-target entry inhibitors.

Clinical benefits of PD-1/PD-L1 inhibitors in patients with metastatic colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Immunotherapy for colorectal cancer has developed rapidly in the past decade. Many high-quality clinical trials examining the application of PD-1/PD-L1 inhibitors in patients with metastatic colorectal cancer (mCRC) have been conducted in recent years. However, the clinical benefits, including the efficacy and safety of these treatments against mCRC, remain controversial. Hence, we conducted this meta-analysis on the clinical benefits of PD-1/PD-L1 inhibitors in patients with mCRC. METHODS: We searched online databases including MEDLINE, Embase, Cochrane Library, and Web of Science, from inception to January 4, 2021. The outcomes related to efficacy and safety were extracted and analyzed. Subgroup analyses were conducted according to the categories of dMMR-MSI-H (tumors with mismatch repair deficiency and high levels of microsatellite instability) ≥ 5% vs. dMMR-MSI-H < 5%, monotherapy vs. combination therapy, PD-1 inhibitors vs. PD-L1 inhibitors, and nivolumab vs. pembrolizumab. RESULTS: Fourteen studies including 1129 subjects were included in our systematic review. The overall complete response (CR), partial response (PR), stable disease (SD), and progression of disease (PD) rates were 0.01 (95% CI 0.00-0.04), 0.04 (95% CI 0.05-0.26), 0.27 (95% CI 0.22-0.32), and 0.44 (95% CI 0.30-0.58), respectively. The overall objective response rate (ORR) and disease control rate (DCR) were 0.16 (95%CI 0.06-0.31) and 0.50 (95%CI 0.35-0.65), respectively. The overall rate of adverse events (AEs) and severe adverse responses (SAEs) were 0.84 (95% CI 0.72-0.92) and 0.30 (95% CI 0.20-0.41), respectively. The ORRs of the dMMR-MSI-H ≥ 5% and dMMR-MSI-H < 5% subgroups were 0.40 (95% CI 0.30-0.51) and 0.04 (95% CI 0.00-0.09), respectively. CONCLUSIONS: PD-1/PD-L1 inhibitors produced encouraging clinical benefits including the response rate in the treatment of dMMR-MSI-H mCRC. They actually have been influenced by the present state of mCRC therapy including pMMR-MSI-L mCRC. Nevertheless, additional multi-center prospective studies are still expected. TRIAL REGISTRATION: We have registered this study in the International Prospective Register of Systematic Reviews (PROSPERO), and the registration number is CRD42021249601 .

BIOMASS YIELD 1 regulates sorghum biomass and grain yield via the shikimate pathway.

Biomass and grain yield are key agronomic traits in sorghum (Sorghum bicolor); however, the molecular mechanisms that regulate these traits are not well understood. Here, we characterized the biomass yield 1 (by1) mutant, which displays a dramatically altered phenotype that includes reduced plant height, narrow stems, erect and narrow leaves, and abnormal floral organs. Histological analysis suggested that these phenotypic defects are mainly caused by inhibited cell elongation and abnormal floral organ development. Map-based cloning revealed that BY1 encodes a 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS) that catalyses the first step of the shikimate pathway. BY1 was localized in chloroplasts and was ubiquitously distributed in the organs examined, particularly in the roots, stems, leaves, and panicles, which was consistent with its role in biomass production and grain yield. Transcriptome analysis and metabolic profiling revealed that BY1 was involved in primary metabolism and that it affected the biosynthesis of various secondary metabolites, especially flavonoids. Taken together, these findings demonstrate that BY1 affects biomass and grain yield in sorghum by regulating primary and secondary metabolism via the shikimate pathway. Moreover, our results provide important insights into the relationship between plant development and metabolism.

Questionable necessity of nitroglycerin for diagnostic coronary artery examination using 320-row multi-detector computed tomography.

OBJECTIVE: This study aims to analyze and compare the diagnostic effectiveness of 320-row multi-detector computed tomography for coronary artery angiography (MDCTA) in subjects with and without sublingual vasodilator (nitroglycerin). MATERIALS AND METHODS: From September 2015 to September 2016, 70 individuals without history of major cardiovascular diseases who underwent MDCTA for health examination were retrospectively categorized into sublingual nitroglycerin (NTG) and non-NTG groups. Medical history, CT dose index (CTDI), and multi-slice CT images were compared between two groups. A diameter of coronary artery (DA, mm) was computed and analyzed. RESULTS: A total of 41 males and 29 females (mean age: 55.43±8.84 years, range: 34- 76) were reviewed. Normal and abnormal MDCTA findings were noted in 54 and 16 participants, respectively, with the detection rate of coronary artery disease being 23%. There was no significant difference in inter-observer variability of coronary CTA image quality and diagnosis between the NTG and non-NTG groups among three experienced radiologists. Although the percentage dilatation of left anterior descending branch (LAD), right coronary artery (RCA) and left circumflex branch (LCX) following in the NTG group were 12.4%, 12.8% and 25.3%, respectively (p < 0.01), there was no significant difference in image quality and diagnosis between the two groups. CONCLUSIONS: Despite the recommendation of routine nitroglycerin use for subjects undergoing computed tomography for coronary artery angiography, our results showed no significant advantage of its use in improving image quality and rate of diagnosis accuracy.

Combination of a Self-Regulation Module and Mobile Application to Enhance Treatment Outcome for Patients with Acne.

Background and Objectives: Acne, an inflammatory disorder of the pilosebaceous unit associated with both physiological and psychological morbidities, should be considered a chronic disease. The application of self-regulation theory and therapeutic patient education has been widely utilized in different health-related areas to help patient with a chronic disease to attain better behavioral modification. The present study aims at investigating the treatment efficacy of combining a self-regulation-based patient education module with mobile application in acne patients. Materials and Methods: This was one-grouped pretest-posttest design at a single tertiary referral center with the enrollment of 30 subjects diagnosed with acne vulgaris. Relevant information was collected before (week 0) and after (week 4) treatment in the present study, including the Acne Self-Regulation Inventory (ASRI), Cardiff Acne Disability Index (CADI), and Dermatology Life Quality Index (DLQI) that involved a questionnaire-based subjective evaluation of the patient's ability in self-regulation and quality of life as well as clinical Acne Grading Scores (AGS) that objectively assessed changes in disease severity. To reinforce availability and feasibility, an individualized platform was accessible through mobile devices for real-time problem solving between hospital visits. Results: Thirty subjects completed the designed experiment. An analysis of the differences between scores of pretest and posttest of ASRI demonstrated substantial elevations (p < 0.001). The questionnaire survey of CADI and DLQI dropped significantly after the application of a self-regulation-based patient education module with a mobile application, revealing substantial reductions in both parameters (p < 0.001). The sign test demonstrated a remarkably significant difference in AGS (Z = -7.38, p < 0.001), indicating notable improvement in the clinical severity of acne after treatment. Conclusions: After incorporating modern mobile application, a self-regulation-based therapeutic patient education module could significantly improve treatment outcomes among acne patients.

Brittle Culm 1 Encodes a COBRA-Like Protein Involved in Secondary Cell Wall Cellulose Biosynthesis in Sorghum.

Plant mechanical strength contributes to lodging resistance and grain yield, making it an agronomically important trait in sorghum (Sorghum bicolor). In this study, we isolated the brittle culm 1 (bc1) mutant and identified SbBC1 through map-based cloning. SbBC1, a homolog of rice OsBC1 and Arabidopsis thaliana AtCOBL4, encodes a COBRA-like protein that exhibits typical structural features of a glycosylphosphatidylinositol-anchored protein. A single-nucleotide mutation in SbBC1 led to reduced mechanical strength, decreased cellulose content, and increased lignin content without obviously altering plant morphology. Transmission electron microscopy revealed reduced cell wall thickness in sclerenchyma cells of the bc1 mutant. SbBC1 is primarily expressed in developing sclerenchyma cells and vascular bundles in sorghum. RNA-seq analysis further suggested a possible mechanism by which SbBC1 mediates cellulose biosynthesis and cell wall remodeling. Our results demonstrate that SbBC1 participates in the biosynthesis of cellulose in the secondary cell wall and affects the mechanical strength of sorghum plants, providing additional genetic evidence for the roles of COBRA-like genes in cellulose biosynthesis in grasses.

Roles of SP600125 in expression of JNK, RANKL and OPG in cultured dental follicle cells.

OBJECTIVE: To investigate the expression of C-JNK, RANKL and OPG after SP600125 administration in cultured dental follicle cells (DFCs). METHODS: TRAP staining and electron microscope were carried out on day 7 and 9 after coculture of BMMs and DFCs with a ratio of 5:1 in different groups. To determine the effects of SP600125 on the expression of C-JNK, RANKL and OPG mRNA and protein, cultured DFCs were divided into control group, DMSO group and SP600125 groups. Real-time PCR and Western blot analysis were performed to investigate the expression of the mRNA and protein, respectively. RESULTS: TRAP assay indicated that the number of multinucleated osteoclasts in the SP600125 group showed significant decrease compared with that of control (P < 0.05). The expression of JNK protein in the SP600125 groups showed significant decline compared with that of the control group and blank control (P < 0.05). Significant decrease was noticed in the RANKL protein expression with the elevation of SP600125. CONCLUSIONS: SP600125 could inhibit the formation of osteoclast in the coculture system of DFCs and BMMs. After SP600125 treatment, the expression of RANKL and JNK showed a trend of decrease, and the expression of OPG showed gradual increase followed by gradual decrease.

Non-dormant Axillary Bud 1 regulates axillary bud outgrowth in sorghum.

Tillering contributes to grain yield and plant architecture and therefore is an agronomically important trait in sorghum (Sorghum bicolor). Here, we identified and functionally characterized a mutant of the Non-dormant Axillary Bud 1 (NAB1) gene from an ethyl methanesulfonate-mutagenized sorghum population. The nab1 mutants have increased tillering and reduced plant height. Map-based cloning revealed that NAB1 encodes a carotenoid-cleavage dioxygenase 7 (CCD7) orthologous to rice (Oryza sativa) HIGH-TILLERING DWARF1/DWARF17 and Arabidopsis thaliana MORE AXILLARY BRANCHING 3. NAB1 is primarily expressed in axillary nodes and tiller bases and NAB1 localizes to chloroplasts. The nab1 mutation causes outgrowth of basal axillary buds; removing these non-dormant basal axillary buds restored the wild-type phenotype. The tillering of nab1 plants was completely suppressed by exogenous application of the synthetic strigolactone analog GR24. Moreover, the nab1 plants had no detectable strigolactones and displayed stronger polar auxin transport than wild-type plants. Finally, RNA-seq showed that the expression of genes involved in multiple processes, including auxin-related genes, was significantly altered in nab1. These results suggest that NAB1 functions in strigolactone biosynthesis and the regulation of shoot branching via an interaction with auxin transport.

Repeated Loading Behavior of Pediatric Porcine Common Carotid Arteries.

Rapid flexion and extension of the neck may occur during scenarios associated with traumatic brain injury (TBI), and understanding the mechanical response of the common carotid artery (CCA) to longitudinal stretch may enhance understanding of contributing factors that may influence CCA vasospasm and exacerbate ischemic injury associated with TBI. Immature (4-week-old) porcine CCAs were tested under subcatastrophic (1.5 peak stretch ratio) cyclic loading at 3 Hz for 30 s. Under subcatastrophic cyclic longitudinal extension, the immature porcine CCA displays softening behavior. This softening can be represented by decreasing peak stress and increasing corner stretch values with an increasing number of loading cycles. This investigation is an important first step in the exploration of fatiguelike behavior in arterial tissue that may be subjected to repeated longitudinal loads.

Validity of combination active specific immunotherapy for colorectal cancer: a meta-analysis of 2993 patients.

BACKGROUND AIMS: The aim of this study was to investigate whether active specific immunotherapy (ASI) is able to demonstrate therapeutic efficacy against colorectal cancer. METHODS: We conducted a systematic review of published papers from MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Wanfang Database, the China Science and Technology Periodical Database and China Journal Net. Published data were extracted independently by two authors who used predefined database templates. The effects of ASI were compared with those of surgery alone, and a pooled analysis was performed with the use of the data from random- or fixed-effect models. RESULTS: Twelve trials matched our inclusion criteria (n = 2993, including 1842 control subjects). The overall analysis showed a significant survival benefit [1-, 2-, 3-, 4-, 5-, 6- and 7-year overall survival (OS), P < 0.05; 10-year OS, P < 0.001] in favor of ASI immunotherapy combined with surgery, but there was not an improvement in the 8- or 9-year OS (P > 0.05). The disease-free survival (DFS) rate was improved after the combination of ASI immunotherapy (2-, 3-, 5- and 10-year DFS, P < 0.05), but no significant improvement was noted for the 1-, 4-, 6-, 7-, 8- or 9-year DFS (P > 0.05). In addition, the disease-specific survival (DSS) was improved at some time points after the combination of ASI immunotherapy and surgery (2-, 3-, 4-, 5- and 6-year DSS, P < 0.05, but not the 1-, 7-, 8- or 9-year DSS, P > 0.05). An improved 2-, 3-, 4-, 5- and 6-year recurrence-free interval (RFI) (P < 0.05) was also observed in patients who received ASI therapy, but this was not observed for the 1-year RFI (P > 0.05). Furthermore, an analysis of the recurrence-free survival (RFS) showed that it was significantly increased in the ASI plus surgery group (1-, 2-, 3-, 4-, 5- and 6-year RFS, P < 0.001). The funnel plots showed that the analyses were relatively reliable and the publication bias was small. CONCLUSIONS: The combination of ASI immunotherapy and surgery was superior in prolonging the overall survival time and enhancing the recurrence-free survival rate compared with surgery alone.

Clinical efficacy of autologous stem cell transplantation for the treatment of patients with type 2 diabetes mellitus: a meta-analysis.

BACKGROUND AIMS: In this study, we investigate whether bone marrow mononuclear cells (BM-MNC) or peripheral blood mononuclear cells (PB-MNC) have therapeutic efficacy in type 2 diabetes (T2D). METHODS: Search terms included stem cell, bone marrow cell, peripheral blood cell, umbilical cord blood and T2D in MEDLINE, the Cochrane Controlled Trials Register, EMBASE, the Wanfang Database, the China Science and Technology Periodical Database and China Journal Net. RESULTS: Fifteen trials met our inclusion criteria (n = 497). One group included 266 cases with BM-MNC therapy and the other group contained 231 cases with PB-MNC treatment. Glycosylated hemoglobin was decreased after BM-MNC or PB-MNC therapy compared with that before (12 months: P < 0.001; 6 months: P < 0.001; 3 months: P < 0.05). Fasting plasma glucose was reduced in BM-MNC therapy group compared with control after 12-month follow-up (P < 0.001) and after BM-MNC therapy compared with that before (9 months: P < 0.001) but was not obvious in other stages. Meanwhile, the analysis showed that C-peptide level increased after BM-MNC and PB-MNC therapy compared with the control therapy (12 months: P < 0.001) and with that before therapy (6 months: P < 0.05). Insulin requirement reduction was also observed in patients receiving BM-MNC therapy (3, 6, 9 and 12 months: P < 0.05). CONCLUSIONS: To a certain extent, BM-MNC or PB-MNC therapy for T2D demonstrated superiority of glycemic control, increased insulin biosynthesis and elevated insulin secretion from existing ß-cells and might prevent islet cell loss.