Traditional, complementary and integrative medicine for fatigue post COVID-19 infection: A systematic review of randomized controlled trials.

Background: Chronic fatigue is a predominant symptom of post COVID-19 condition, or long COVID. We aimed to evaluate the efficacy and safety of Traditional, Complementary and Integrative Medicine (TCIM) for fatigue post COVID-19 infection. Methods: Ten English and Chinese language databases and grey literature were searched up to 12 April 2023 for randomized controlled trials (RCTs). Cochrane "Risk of bias" (RoB) tool was applied. Evidence certainty was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Effect estimates were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Results: Thirteen RCTs with 1632 participants were included. One RCT showed that Bufei Huoxue herbal capsules reduced fatigue (n=129, MD -14.90, 95%CI -24.53 to -5.27), one RCT reported that Ludangshen herbal liquid lowered fatigue (n=184, MD -1.90, 95%CI -2.38 to -1.42), and the other one RCT shown that fatigue disappearance rate was higher with Ludangshen herbal liquid (n=184, RR 4.19, 95%CI 2.06 to 8.53). Compared to traditional Chinese medicine rehabilitation (TCM-rahab) alone, one RCT showed that fatigue symptoms were lower following Qingjin Yiqi granules plus TCM-rehab (n=388, MD -0.48, 95%CI -0.50 to -0.46). Due to concerns with RoB and/or imprecision, the certainty in this evidence was low to very low. No serious adverse events was reported. Conclusions: Limited evidence suggests that various TCIM interventions might reduce post COVID-19 fatigue. Larger, high quality RCTs of longer duration are required to confirm these preliminary findings. Study Registration: The protocol of this review has been registered at PROSPERO: CRD42022384136.

Immunologic Crosstalk of Endoplasmic Reticulum Stress Signaling in Bladder Cancer.

Bladder cancer (BC) is a common malignant tumor of the urinary system. While current approaches involving adjuvant chemotherapy, radiotherapy, and immunotherapy have shown significant progress in BC treatment, challenges, such as recurrence and drug resistance, persist, especially in the case of muscle-invasive bladder cancer (MIBC). This is mainly due to the lack of pre-existing immune response cells in the tumor immune microenvironment. Micro-environmental changes (such as hypoxia and under-nutrition) can cause the aggregation of unfolded and misfolded proteins in the lumen, which induces endoplasmic reticulum (ER) stress. ER stress and its downstream signaling pathways are closely related to immunogenicity and tumor drug resistance. ER stress plays a pivotal role in a spectrum of processes within immune cells and the progression of BC cells, encompassing cell proliferation, autophagy, apoptosis, and resistance to therapies. Recent studies have increasingly recognized the potential of natural compounds to exhibit anti-BC properties through ER stress induction. Still, the efficacy of these natural compounds remains less than that of immune checkpoint inhibitors (ICIs). Currently, the ER stress-mediated immunogenic cell death (ICD) pathway is more encouraging, which can enhance ICI responses by mediating immune stemness. This article provides an overview of the recent developments in understanding how ER stress influences tumor immunity and its implications for BC. Targeting this pathway may soon emerge as a compelling therapeutic strategy for BC.

Exploring potential targets of HPV&BC based on network pharmacology and urine proteomics.

BACKGROUND: Bladder cancer (BC) caused by Human papillomavirus (HPV) infection remains a complex public health problem in developing countries. Although the HPV vaccine effectively prevents HPV infection, it does not benefit patients with BC who already have HPV. METHODS: Firstly, the differential genes of HPV-related BC patients were screened by transcriptomics, and then the prognostic and clinical characteristics of the differential genes were analyzed to screen out the valuable protein signatures. Furthermore, the compound components and targets of Astragali Radix (AR) were analyzed by network pharmacology, and the intersection targets of drug components and HPV_BC were screened out for pathway analysis. In addition, the binding ability of the compound to the Astragali-HPV_BC target was verified by molecular docking and virtual simulation. Finally, to identify potential targets in BC patients through urine proteomics and in vitro experiments. RESULTS: Eleven HPV_BC-related protein signatures were screened out, among which high expression of EGFR, CTNNB1, MYC, GSTM1, MMP9, CXCR4, NOTCH1, JUN, CXCL12, and KRT14 had a poor prognosis, while low expression of CASP3 had a poor prognosis. In the analysis of clinical characteristics, it was found that high-risk scores, EGFR, MMP9, CXCR4, JUN, and CXCL12 tended to have higher T stage, pathological stage, and grade. Pharmacological and molecular docking analysis identified a natural component of AR (Quercetin) and it corresponding core targets (EGFR). The OB of the natural component was 46.43, and the DL was 0.28, respectively. In addition, EGFR-Quercetin has high affinity. Urine proteomics and RT-PCR showed that EGFR was expressed explicitly in BC patients. Mechanism analysis revealed that AR component targets might affect HPV_BC patients through Proteoglycans in the cancer pathway. CONCLUSION: AR can target EGFR through its active component (Quercetin), and has a therapeutic effect on HPV_BC patients.

Mechanism of action of icaritin on uterine corpus endometrial carcinoma based on network pharmacology and experimental evaluation.

Background: Uterine corpus endometrial carcinoma (UCEC) belongs to a group of epithelial malignant tumors. Icaritin is the main active compound of Epimedii Folium. Icaritin has been utilized to induce UCEC cells to death. Methods: We wished to identify potential targets for icaritin in the treatment of UCEC, as well as to provide a groundwork for future studies into its pharmacologic mechanism of action. Network pharmacology was employed to conduct investigations on icaritin. Target proteins were chosen from the components of icaritin for UCEC treatment. A protein-protein interaction (PPI) network was established using overlapping genes. Analyses of enrichment of function and signaling pathways were undertaken using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively, to select "hub genes". Finally, experiments were carried out to ascertain the effect of icaritin on endometrial cancer (HEC-1-A) cells. Results: We demonstrated that icaritin has bioactive components and putative targets that are therapeutically important. Icaritin treatment induced sustained activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt pathway) and inhibited growth of HEC-1-A cells. Conclusion: Our data provide a rationale for preclinical and clinical evaluations of icaritin for UCEC therapy.

Perioperative and oncologic outcomes of minimally-invasive surgery for renal cell carcinoma with venous tumor thrombus: a systematic review and meta-analysis of comparative trials.

BACKGROUND: The present study aimed to conduct a pooled analysis to compare the perioperative and oncologic outcomes of minimally-invasive radical nephrectomy with tumor thrombus (MI-RNTT) with open radical nephrectomy with tumor thrombus (O-RNTT). METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Four electronic databases (PubMed, Embase, Web of Science, and the Cochrane Library database) were systematically searched to identify relevant studies published in English up to December 2022. The primary outcomes were perioperative results, complications, and oncologic outcomes. Review Manager 5.4 was used for this analysis. RESULTS: In total, eight retrospective trials with a total of 563 patients were included. Compared to O-RNTT, MI-RNTT had shorter hospitalization time [weighted mean difference (WMD) -3.58 days, 95% CI: -4.56 to -2.59; P <0.00001), lower volumes of blood loss (WMD -663.32 ml, 95% CI: -822.22 to -504.42; P <0.00001), fewer transfusion rates (OR 0.18, 95% CI: 0.09-0.35; P <0.00001), fewer overall complications (OR 0.33, 95% CI: 0.22-0.49; P <0.00001), and fewer major complications s (OR 0.49, 95% CI: 0.24-1.00; P =0.05). However, operative time, intraoperative complications, mortality rate (intraoperative, within 30 days, and total mortality), overall survival, recurrence-free survival, and cancer-specific survival did not significantly differ between the two groups. CONCLUSIONS: MI-RNTT possesses more benefits than O-RNTT in terms of length of hospital stay, blood loss, and complications and provides comparable mortality rates and oncologic outcomes. However, more comprehensive and rigorous research is warranted to further validate the outcomes, which should include a larger sample size and comprehensive data from high-volume medical centers.

Comparison of upfront versus deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma receiving systemic therapy: a systematic review and meta-analysis.

BACKGROUND: This study aimed to conduct a pooled analysis to compare the outcomes of patients with metastatic renal cell carcinoma who received presurgical systemic therapy [(ST); including immunotherapy and/or targeted therapy] followed by cytoreductive nephrectomy (CN) [(deferred CN; (dCN)] with those who underwent upfront CN (uCN) followed by ST. METHODS: The present study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A comprehensive search was conducted in PubMed, Embase, Web of Science, Scopus, and the Cochrane Library database to identify eligible comparative studies up to April 2023. To evaluate their relevance, pooled hazard ratio with 95% CIs were calculated. RESULTS: A total of 3157 patients were included in nine studies. The dCN group was observed to be correlated with superior overall survival (OS) compared to the uCN group (hazard ratio =0.71, 95% CI 0.57-0.89, P =0.003). Moreover, the authors conducted subgroup analyses according to the type of ST, sample size, sex, age, and risk score, and observed similar outcomes for OS across most subgroups. CONCLUSIONS: The results of this study demonstrated that dCN may be associated with improved OS compared to uCN in patients with metastatic renal cell carcinoma receiving ST. However, no significant differences were found between the uCN and dCN groups in the immunotherapy-based combinations subgroup. Further research is needed to confirm these results.

Influence of a topological artificial atom chain on the transmission properties of a cavity.

We explore the influence of the artificial atomic chain on the input-output relation of the cavity. Specifically, we extend the atom chain to the one-dimensional Su-Schrieffer-Heeger (SSH) chain to check the role of atomic topological non-trivial edge state on the transmission characteristics of the cavity. The superconducting circuits can realize the artificial atomic chain. Our results show that the atom chain is not equivalent to atom gas, and the transmission properties of the cavity containing the atom chain are entirely different from that of the cavity containing atom gas. When the atom chain is arranged in the form of topological non-trivial SSH model, the atom chain can be equivalent to the three-level atom, in which the edge state contributes to the second level and is resonant with the cavity, while the high-energy bulk state contributes to form the third level and is greatly detuned with the cavity. Therefore, the transmission spectrum shows no more than three peaks. This allows us to infer the topological phase of the atomic chain and the coupling strength between the atom and the cavity only from the profile of the transmission spectrum. Our work is helping to understand the role of topology in quantum optics.

Comparison between minimally invasive partial nephrectomy and open partial nephrectomy for complex renal tumors: a systematic review and meta-analysis.

BACKGROUND: The present study aimed to conduct a pooled analysis to compare the efficacy and safety of minimally invasive partial nephrectomy (MIPN) with open partial nephrectomy (OPN) in patients with complex renal tumors (defined as PADUA or RENAL score ≥7). METHODS: The present study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, Supplemental Digital Content 1, http://links.lww.com/JS9/A394 . We conducted a systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases until October 2022. MIPN and OPN-controlled trials for complex renal tumors were included. The primary outcomes were perioperative results, complications, renal function, and oncologic outcomes. RESULTS: A total of 2405 patients were included in 13 studies. MIPN outperformed OPN in terms of hospital stay [weighted mean difference (WMD) -1.84 days, 95% CI -2.35 to -1.33; P <0.00001], blood loss (WMD -52.42 ml, 95% CI -71.43 to -33.41; P <0.00001), transfusion rates [odds ratio (OR) 0.34, 95% CI 0.17-0.67; P =0.002], major complications (OR 0.59, 95% CI 0.40-0.86; P =0.007) and overall complications (OR 0.43, 95% CI 0.31-0.59; P <0.0001), while operative time, warm ischemia time, conversion to radical nephrectomy rates, estimated glomerular decline, positive surgical margins, local recurrence, overall survival, recurrence-free survival, and cancer-specific survival were not significantly different. CONCLUSIONS: The present study demonstrated that MIPN was associated with a shorter length of hospital stay, less blood loss, and fewer complications in treating complex renal tumors. MIPN may be considered a better treatment for patients with complex tumors when technically feasible.

Comparison between robot-assisted versus open nephroureterectomy for upper tract urothelial carcinoma: outcomes from a pooled analysis.

The present study aimed to compare the efficacy and safety between robot-assisted nephroureterectomy (RANU) and open nephroureterectomy (ONU) for the treatment of upper tract urothelial carcinoma (UTUC). We systematically searched four electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) to locate pertinent studies published in English up to January 2023. The primary outcomes evaluated included perioperative results, complications, and oncologic outcomes. Statistical analyses and calculations were performed using Review Manager 5.4. The study was registered with PROSPERO (ID: CRD42022383035). In total, eight comparative trials, including 37,984 patients were enrolled. Compared to ONU, RANU was associated with a significantly shorter length of stay (weighted mean difference [WMD] - 1.63 days, 95% confidence interval [CI] - 2.90, - 0.35; p = 0.01), less blood loss (WMD - 107.04 mL, 95% CI - 204.97, - 9.11; p = 0.03), less major complication(OR 0.78, 95% CI 0.70, 0.88; p < 0.0001), and lower positive surgical margin (PSM) (OR 0.33, 95% CI 0.12, 0.92; p = 0.03). However, no statistically significant differences were observed between the two groups in operative time, transfusion rates, rate of lymph node dissection, lymph node yield, overall complications, overall survival, cancer-specific survival, recurrence-free survival, and progression-free survival. RANU has superior advantages compared to ONU in terms of length of hospital stay, blood loss, postoperative complications, and PSM, while providing comparable oncologic outcomes in patients with UTUC.

The impact of cytoreductive nephrectomy on survival outcomes in patients with metastatic renal cell carcinoma receiving immunotherapy: An evidence-based analysis of comparative outcomes.

Purpose: The prognostic impact of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of immunotherapy is yet to be determined. The aim of our study is to evaluate the correlation between CN and outcomes in the setting of mRCC treated with immunotherapy. Methods: We conducted a systematic search of the Science, PubMed, Web of Science, and Cochrane Library databases to identify relevant studies published in English up to December 2022. The results were presented as hazard ratio (HR) with 95% confidence intervals (CIs) for overall survival (OS) was extracted to assess their relevance. The study was registered with PROSPERO (CRD42022383026). Results: A total of 2397 patients were included in eight studies. The CN group was observed to be correlated with superior OS compared to the No CN group (HR = 0.53, 95% CI 0.39-0.71, p < 0.0001). Subgroup analysis according to the type of immunotherapy, sample size, and treatment line of immune checkpoint inhibitor revealed that CN group had a superior OS in all subgroups. Conclusion: CN is associated with a better outcome in terms of OS benefit in selected patients with mRCC treated by immunotherapy, but further studies are required to verify the conclusions. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022383026.

Perioperative, functional, and oncologic outcomes of robot-assisted versus open partial nephrectomy for complex renal tumors (RENAL score ≥ 7): an evidence-based analysis.

This study aims to assess the efficacy and safety of robot-assisted partial nephrectomy (RAPN) compared with open partial nephrectomy (OPN) in the management of complex renal tumors (defined as RENAL score ≥ 7). We conducted a comprehensive literature search in PubMed, Embase, Web of Science, and Cochrane Library to identify relevant comparative studies up to January 2023. This study was conducted with the Review Manager 5.4 software, and included RAPN and OPN-controlled trials for complex renal tumors. The prime outcomes were to assess the perioperative results, complications, renal function, and oncologic outcomes. A total of 1493 patients were included in seven studies. Compared to OPN, RAPN was associated with a significantly shorter hospital stay (weighted mean difference [WMD] - 1.53 days, 95% confidence interval [CI] - 2.44, - 0.62; p = 0.001), less blood loss (WMD - 95.88 mL, 95% CI - 144.19, - 47.56; p = 0.0001), lower transfusion rates (OR 0.33, 95% CI 0.15, 0.71; p = 0.005), fewer major complications (OR 0.63, 95% CI 0.39, 1.01; p = 0.05), and fewer overall complications (OR 0.49, 95% CI 0.36, 0.65; p < 0.00001). Nevertheless, no statistically significant differences were found between the two groups in operative time, warm ischemia time, estimated glomerular decline, intraoperative complications, positive surgical margins, local recurrence, overall survival, and recurrence-free survival. The study demonstrated that RAPN had superior perioperative parameters and fewer complications when compared to OPN for complex renal tumors. However, no significant differences were found in terms of renal function and oncologic outcomes.

The Feature of Sleep Spindle Deficits in Patients With Schizophrenia With and Without Auditory Verbal Hallucinations.

BACKGROUND: Previous sleep electroencephalography studies have detected abnormalities in sleep architecture and sleep spindle deficits in schizophrenia (SCZ), but the consistency of these results was not robust, which might be due to the small sample size and the influence of clinical factors such as the various medication therapies and symptom heterogeneity. This study aimed to regard auditory verbal hallucinations (AVHs) as a pointcut to downscale the heterogeneity of SCZ and explore whether some sleep architecture and spindle parameters were more severely impaired in SCZ patients with AVHs compared with those without AVHs. METHODS: A total of 90 SCZ patients with AVHs, 92 SCZ patients without AVHs, and 91 healthy control subjects were recruited, and parameters of sleep architecture and spindle activities were compared between groups. The correlation between significant sleep parameters and clinical indicators was analyzed. RESULTS: Deficits of sleep spindle activities at prefrontal electrodes and intrahemispheric spindle coherence were observed in both AVH and non-AVH groups, several of which were more serious in the AVH group. In addition, deficits of spindle activities at central and occipital electrodes and interhemispheric spindle coherence mainly manifested accompanying AVH symptoms, most of which were retained in the medication-naive first-episode patients, and were associated with Auditory Hallucination Rating Scale scores. CONCLUSIONS: Our results suggest that the underlying mechanism of spindle deficits might be different between SCZ patients with and without AVHs. In the future, the sleep feature of SCZ patients with different symptoms and the influence of clinical factors, such as medication therapy, should be further illustrated.

Perioperative and oncologic outcomes of single-port versus conventional robotic-assisted partial nephrectomy: an evidence-based analysis of comparative outcomes.

This study aims to evaluate the effectiveness and safety between single-port robotic-assisted partial nephrectomy (da Vinci SP system) with conventional robotic-assisted partial nephrectomy (da Vinci Si or Xi system). We systematically searched PubMed, Science Embase, Web of Science and Cochrane Library database for articles comparing single-port robotic-assisted partial nephrectomies (SP-RAPN) and conventional robotic-assisted partial nephrectomy (Con-RAPN) till September 2022. The principal outcomes included perioperative outcomes, complications, and oncologic outcomes were evaluated. A total of 586 patients were included in six studies. There were no significant differences in operative time (p = 0.19), transfusion rates (p = 0.11), off-clamp (p = 0.32), total perioperative milligram morphine equivalents (MME) (p = 0.44), intraoperative complications (p = 0.60), major complications (p = 0.84), overall complications (p = 0.90), positive surgical margins (PSM) (p = 0.75) and local recurrence (p = 0.50) between SP-RAPN and Con-RAPN. In addition, the marginal results were recorded in length of hospital stay subgroup (WMD - 0.35 days, 95% CI - 0.70, 0.01; p = 0.06) and blood loss (WMD - 27.16 ml, 95% CI - 56.90, 2.58; p = 0.07). However, SP-RAPN had longer warm ischemia time compared to Con-RAPN (WMD 3.42 min, 95% CI 1.71, 5.13; p < 0.0001). The results of this study demonstrated that SP-RAPN provided similar effectiveness and safety to Con-RAPN, while SP-RAPN might be associated with a marginally shorter length of hospital stay and less blood loss.

Synergistic nanowire-assisted electroporation and chlorination for inactivation of chlorine-resistant bacteria in drinking water systems via inducing cell pores for chlorine permeation.

The widespread use of chlorination (Cl2) in drinking water systems causes the selection of chlorine-resistant bacteria commonly with dense extracellular polymeric substance (EPS) against chlorine permeation, posing significant threat to public health. Herein, a nanowire-assisted electroporation (EP) via locally enhanced electric field was combined with Cl2 to construct the synergistic EP/Cl2 disinfection, with the purposes of inducing cell pores for chlorine permeation and bacterial inactivation. The synergistic effects of EP/Cl2 were observed for inactivation of chlorine-resistant Bacillus cereus (G+, 304 µg DOC-EPS/109 CFU) and Aeromonas media (G-, 35.8 µg), and chlorine-sensitive Escherichia coli (G-, 5.1 µg) that were frequent occurrence in drinking water systems. The EP/Cl2 enabled above 6 log B. cereus inactivation (undetectable live bacteria) at 1.5 V-EP and 0.9 mg/L-Cl2, which was much higher than the individual EP (1.11 log) and Cl2 (1.13 log) disinfection. The cell membrane integrity, intracellular free chlorine levels, and morphology analyses revealed that the electroporation-induced pores on cell wall/membrane destructed the bound EPS barrier for chlorine permeation, and the pore sizes were further enlarged by chlorine oxidation, hence facilitating bacterial inactivation via destroying the cell structures. The excellent disinfection performance for tap water and lake water also suggested its sound application potentials.

[Post-stroke shoulder-hand syndrome of phlegm-stasis obstruction treated with the combined therapy of eye acupuncture, Tengliao and rehabilitation training: a multi-central randomized controlled trial].

OBJECTIVE: To assess the efficacy on relieving pain and improving the range of motion of shoulder joint in post-stroke shoulder-hand syndrome of phlegm-stasis obstruction in treatment of the combined therapy of eye acupuncture, Tengliao (Chinese herbal warm dressing technique) and rehabilitation training (eye acupuncture + Tengliao + rehabilitation) as compared with the combined treatment of Tengliao and rehabilitation training (Tengliao + rehabilitation) and the simple rehabilitation training (rehabilitation). METHODS: A total of 356 patients with post-stroke shoulder-hand syndrome of phlegm-stasis obstruction were randomized into an eye acupuncture + Tengliao + rehabilitation group (group A, 122 cases, 2 cases dropped off), a Tengliao + rehabilitation group (group B, 120 cases, 3 cases dropped off) and a rehabilitation group (group C, 114 cases, 1 case dropped off). In the group C, the basic treatment was combined with routine rehabilitation training. In the group B, on the base of the treatment as the group C, Tengliao was exerted. A medical bag composed of over 20 Chinese herbal materials was heated and dressed at the affected area, 30 min each time, 5 times weekly. In the group A, besides the treatment as the group B, eye acupuncture was applied to heart region, kidney region, upper jiao region and lower jiao region, 30 min each time, 5 times weekly. The treatment lasted 28 days in all of three groups. Separately, before treatment, in 7, 14, 21 and 28 days of treatment, as well as in 14 days after treatment of follow-up, the score of visual analogue scale (VAS) for pain, the score of guides to evaluation of permanent impairment (GEPI) and the score of National Institutes of Health stroke scale (NIHSS) were observed in each group. RESULTS: The scores of VAS, GEPI and NIHSS were all improved with the treatment lasting in the three groups (P<0.000 1). In 7, 14, 21 and 28 days of treatment and in follow-up as well, VAS scores in the group A were all lower than the group C (P<0.05). After 14 days of treatment, GEPI score showed increasing trend, while NIHSS score showed decreasing trend in the group A compared with the group B. Before treatment, GEPI score was lower and NIHSS score was higher in the group A compared with the group C (P<0.05). It was suggested that the illness was slightly serious in the group A. After propensity score matching, in 14, 21 and 28 days as well as in follow-up, GEPI scores in the group A were higher than the group C respectively (P<0.05). Regarding NIHSS score at each time point, the difference had no statistical significance between the group A and the group C (P>0.05). CONCLUSION: The combined therapy of eye acupuncture, Tengliao and rehabilitation training obtains a better efficacy on post-stroke shoulder-hand syndrome of phlegm-stasis obstruction as compared with rehabilitation training.

Genome-wide analysis of cell-Free DNA methylation profiling with MeDIP-seq identified potential biomarkers for colorectal cancer.

BACKGROUND: Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis. METHODS: Peripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets. RESULTS: Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data. CONCLUSIONS: MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer.

Estimations of Water Use Efficiency in Winter Wheat Based on Multi-Angle Remote Sensing.

Real-time non-destructive monitoring of water use efficiency (WUE) is important for screening high-yielding high-efficiency varieties and determining the rational allocation of water resources in winter wheat production. Compared with vertical observation angles, multi-angle remote sensing provides more information on mid to lower parts of the wheat canopy, thereby improving estimates of physical and chemical indicators of the entire canopy. In this study, multi-angle spectral reflectance and the WUE of the wheat canopy were obtained at different growth stages based on field experiments carried out across 4 years using three wheat varieties under different water and nitrogen fertilizer regimes. Using appropriate spectral parameters and sensitive observation angles, the quantitative relationships with wheat WUE were determined. The results revealed that backward observation angles were better than forward angles, while the common spectral parameters Lo and NDDAig were found to be closely related to WUE, although with increasing WUE, both parameters tended to become saturated. Using this data, we constructed a double-ratio vegetation index (NDDAig/FWBI), which we named the water efficiency index (WEI), reducing the impact of different test factors on the WUE monitoring model. As a result, we were able to create a unified monitoring model within an angle range of -20-10°. The equation fitting determination coefficient (R 2) and root mean square error (RMSE) of the model were 0.623 and 0.406, respectively, while an independent experiment carried out to test the monitoring models confirmed that the model based on the new index was optimal, with R 2, RMSE, and relative error (RE) values of 0.685, 0.473, and 11.847%, respectively. These findings suggest that the WEI is more sensitive to WUE changes than common spectral parameters, while also allowing wide-angle adaptation, which has important implications in parameter design and the configuration of satellite remote sensing and UAV sensors.

Melatonin promotes potassium deficiency tolerance by regulating HAK1 transporter and its upstream transcription factor NAC71 in wheat.

Melatonin (MT) is involved in various physiological processes and stress responses in animals and plants. However, little is known about the molecular mechanisms by which MT regulates potassium deficiency (DK) tolerance in crops. In this study, an appropriate concentration (50 µmol/L) was found to enhance the tolerance of wheat plants against DK. RNA-seq analysis showed that a total of 6253 and 5873 differentially expressed genes (DEGs) were separately identified in root and leaf tissues of the DK + MT-treated wheat plants. They functionally involved biological processes of secondary metabolite, signal transduction, and transport or catabolism. Of these, an upregulated high-affinity K transporter 1 (TaHAK1) gene was next characterized. TaHAK1 overexpression markedly enhanced the K absorption, while its transient silencing exhibited the opposite effect, suggesting its important role in MT-mediated DK tolerance. Moreover, yeast one-hybrid (Y1H) was used to screen the upstream regulators of TaHAK1 gene and the transcription factor TaNAC71 was identified. The binding between TaNAC71 and TaHAK1 promoter was evidenced by using Y1H, LUC, and EMSA assays. Transient overexpression of TaNAC71 in wheat protoplasts activated the TaHAK1 expression, whereas its transient silencing inhibited the TaHAK1 expression and aggravated the sensitivity to DK. Exogenous MT application greatly upregulated the expression of TaHAK1 in both transient overexpression and silencing systems. Our findings revealed some molecular mechanisms underlying MT-mediated DK tolerance and helped broaden its practical application in agriculture.

Inhibition of macrophage migration inhibitory factor prevents thyroid dysfunction in pregnant rats with acute pancreatitis.

Acute pancreatitis during pregnancy (APIP) rarely occurs but may lead to preterm delivery and be associated with high fetal mortality. Macrophage migration inhibitory factor (MIF) participates in various inflammatory diseases as a pro-inflammatory cytokine. In this study, we aimed to explore the effects of (S, R)-3-(4-hydroxyphenyl)-4, 5dihydro-5-isoxazole acetic methyl ester (ISO-1), an inhibitor of MIF, on maternal thyroid injury associated with APIP and its potential mechanisms in a pregnant rat model. APIP model was induced by retrograde injection of sodium taurocholate. ISO-1 was injected intraperitoneally 30 min before model establishment. The severity of pancreatitis was assessed by levels of tumor necrosis factor (TNF)­α, interleukin (IL)­1ß, IL-6 of maternal serum as well as histopathological score. Thyroid injury was determined by free triiodothyronine (FT3), free tetraiodothyronine (FT4) and thyroid histopathological score. Levels of MIF in maternal serum and the expression of MIF, CD68, CD3 and intercellular cell adhesion molecule-1 (ICAM-1) as well as oxidative stress status in maternal thyroid tissues were detected. Ultrastructure of maternal thyroid tissues was observed by transmission electron microscope. Thyroid injuries occurred in APIP and the lesions were attenuated with the pretreatment of ISO-1. Moreover, ISO-1 reduced the expression of MIF, attenuated the activations of CD68, CD3, ICAM-1 while improved oxidative stress status in maternal thyroid. Our research suggested a protective role of ISO-1 on thyroid injury and endocrine disorder during APIP, which may be associated with the inhibition of biological functions of MIF.