Synchronous removal of gaseous toluene and benzene and degradation process shifts in microbial fuel cell-biotrickling filter system.

Illustrating the biodegradation processes of multi-component volatile organic compounds (VOCs) will expedite the implication of biotechnology in purifying industrial exhaust. Here, performance shifts of microbial fuel cell and biotrickling filter combined system (MFC-BTF) are investigated for removing single and dual components of toluene and benzene. Synchronous removal of toluene (95 %) and benzene (97 %) are achieved by MFC-BTF accompanied with the output current of 0.41 mA. Elevated content of extracellular polymeric substance facilitates the mass transfer of benzene with the presence of toluene. Strains of Bacteroidota, Proteobacteria and Chloroflexi contribute to the removal of dual components VOCs. Empty bed reaction time and the VOCs concentration are the important factors influencing their dissolution in the system. The biodegradation of toluene and benzene proceeds with 2-hydroxymuconic semialdehyde and o-hydroxybenzoic acid as the main intermediates. These results provide a comprehensive understanding of multi-component VOCs removal by MFC-BTF and guide the system design, optimization, and scale-up.

Efficacy and safety of adjuvant topical application of botanicals in the treatment of melasma: A systematic review and meta-analysis.

Objective: To systematically evaluate the efficacy and safety of topical application of botanical (TAB) adjuvants in the treatment of melasma and provide evidence-based medical evidence for their clinical application. Methods: Medline, Web of Science, EMBASE, Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, databases were searched to identify all randomized controlled clinical trials on TAB adjuvant treatment for melasma from inception to May 2023. The primary outcomes included clinical efficacy, adverse effects, recurrence rate, and melanin index. Subgroup analyses were performed using the Melasma Area Severity Index (MASI) scores. Results: This study included 16 randomized trials with 1386 participants. Eligible trials demonstrated that topical phytomedicine adjuvant treatment for melasma increased clinical effectiveness (RR = 1.14, 95% CI (1.10, 1.19), P ＜0.00001), decreased recurrence rate (RR = 0.28, 95% CI (0.13, 0.59), P = 0.0009), and decreased melanin index (MI) (MD = -22.2,95% CI (-31.79, -12.61), P < 0.00001). In addition, subgroup analysis showed that topical phytomedicines reduced MASI scores (I2 = 0%, MDI = -0.95, 95% CI (-1.23,0.67), P < 0.00001), but when scored as the rate of decrease in MASI, topical phytomedicines had high MASI scores (I2 = 15%, MD = 0.3, 95% CI (0, 0.59), P = 0.05), indicating a slower rate of melasma mitigation when botanicals were applied topically. Although burning pain, redness and other mild adverse reactions may occur during the treatment period, they can be recovered on their own, and there is no statistical significance in the comparison of the two groups (RR = 0.95, 95% CI (0.42, 2.51), P = 0.91). Conclusion: TAB for melasma has a clear adjuvant clinical efficacy, a low recurrence rate, and does not cause serious adverse effects. An appropriate administration method may achieve better efficacy; however, this requires further verification.

Differential clinical outcomes after 3 versus 5 years in a comparison of preoperative chemotherapy with and without radiotherapy in locally advanced rectal cancer: A national cohort propensity score-matched study.

Background: Preoperative chemotherapy alone might be a good alternative to preoperative chemoradiotherapy for patients with locally advanced rectal cancer, yet long-term real-world data from the same cohort are lacking. Methods: Patients diagnosed with stage II-III rectal adenocarcinoma from 2011 to 2015 were randomly sampled from the SEER-Plus database to evaluate the superiority of preoperative chemoradiotherapy versus preoperative chemotherapy alone. Findings: A total of 1314 eligible patients were enrolled, with a median follow-up of 74.0 months. At 3-year follow-up, neither overall survival (OS) nor cancer-specific survival (CSS) was significantly different between the two treatment groups. At 5-year follow-up, CSS was similar across groups (HR 0.768, 95% CI 0.532-1.108; P = 0.156), but the 5-year OS was significantly better in the preoperative chemoradiotherapy group than in the preoperative chemotherapy group (HR 0.682, 95% CI 0.538-0.866; P = 0.002). Besides, the landmark analysis indicated a direct contrast in the CSS within 3 years (HR 1.101, 95% CI 0.598-2.029; P = 0.756) versus that at 3-5 years (HR 0.597, 95% CI 0.377-0.948; P = 0.027). The landmark analysis also showed directly contrasting OS outcomes within 3 years (HR 0.761, 95% CI 0.533-1.086; P = 0.130) versus those at 3-5 years (HR 0.621, 95% CI 0.451-0.857; P = 0.003). Interpretation: In patients with locally advanced rectal cancer under real-world treatment practices, the addition of preoperative radiotherapy to chemotherapy improves survival outcomes at 3-5 years' follow-up but not at 3-year follow-up.

Outcomes of preoperative chemotherapy for colorectal cancer with peritoneal metastasis underwent cytoreductive surgery

Background This study aims to assess and compare the extent to which preoperative chemotherapy prior to CRS improves survival in patients diagnosed with CRCPM. Methods We included 251 patients from 2012 to 2019 in our center. Inverse probability of treatment weighting (IPTW) analysis was used to minimize the selection bias. Survival analysis was performed to compare the survival outcomes. Multivariate Cox regression analysis was conducted to identify prognostic factors. Result The baseline characteristics were well balanced using IPTW (standardized mean difference < 0.1). Preoperative chemotherapy cannot significantly improve overall survival (HR, 1.03; 95% CI 0.71–1.49; P = 0.88). In subgroup analysis, we found that intestinal obstruction after preoperative chemotherapy significantly reduced survival (HR, 2.25; 95% CI 1.01–5.03; P = 0.048), while in the upfront surgery group, intestinal obstruction had no impact on prognosis. Conclusion For CRCPM patients treated with CRS, preoperative chemotherapy does not seem to prolong overall survival. Furthermore, the emergence of intestinal obstruction after chemotherapy may compromise the effectiveness of treatment, resulting in a worse prognosis. This finding has important clinical implications for treatment decisions (AU)

Characteristics of the a sequence of the duck Plague virus genome and specific cleavage of the viral genome based on the a sequence.

During the replication process, the herpesvirus genome forms the head-to-tail linked concatemeric genome, which is then cleaved and packaged into the capsid. The cleavage and packing process is carried out by the terminase complex, which specifically recognizes and cleaves the concatemeric genome. This process is governed by a cis-acting sequence in the genome, named the a sequence. The a sequence and genome cleavage have been described in some herpesviruses, but it remains unclear in duck plague virus. In this study, we analysed the location, composition, and conservation of a sequence in the duck plague virus genome. The structure of the DPV genome has an a sequence of (DR4)m-(DR2)n-pac1-S termini (32 bp)-L termini (32 bp)-pac2, and the length is 841 bp. Direct repeat (DR) sequences are conserved in different DPV strains, but the number of DR copies is inconsistent. Additionally, the typical DR1 sequence was not found in the DPV a sequence. The Pac1 and pac2 motifs are relatively conserved between DPV and other herpesviruses. Cleavage of the DPV concatemeric genome was detected, and the results showed that the DPV genome can form a concatemer and is cleaved into a monomer at a specific site. We also established a sensitive method, TaqMan dual qRT‒PCR, to analyse genome cleavage. The ratio of concatemer to total viral genome was decreased during the replication process. These results will be critical for understanding the process of DPV genome cleavage, and the application of TaqMan dual qRT‒PCR will greatly facilitate more in-depth research.

Outcomes of preoperative chemotherapy for colorectal cancer with peritoneal metastasis underwent cytoreductive surgery.

BACKGROUND: This study aims to assess and compare the extent to which preoperative chemotherapy prior to CRS improves survival in patients diagnosed with CRCPM. METHODS: We included 251 patients from 2012 to 2019 in our center. Inverse probability of treatment weighting (IPTW) analysis was used to minimize the selection bias. Survival analysis was performed to compare the survival outcomes. Multivariate Cox regression analysis was conducted to identify prognostic factors. RESULT: The baseline characteristics were well balanced using IPTW (standardized mean difference < 0.1). Preoperative chemotherapy cannot significantly improve overall survival (HR, 1.03; 95% CI 0.71-1.49; P = 0.88). In subgroup analysis, we found that intestinal obstruction after preoperative chemotherapy significantly reduced survival (HR, 2.25; 95% CI 1.01-5.03; P = 0.048), while in the upfront surgery group, intestinal obstruction had no impact on prognosis. CONCLUSION: For CRCPM patients treated with CRS, preoperative chemotherapy does not seem to prolong overall survival. Furthermore, the emergence of intestinal obstruction after chemotherapy may compromise the effectiveness of treatment, resulting in a worse prognosis. This finding has important clinical implications for treatment decisions.

Low-intensity pulsed ultrasound alleviates doxorubicin-induced cardiotoxicity via inhibition of S100a8/a9-mediated cardiac recruitment of neutrophils.

Doxorubicin (DOX)-induced cardiotoxicity limits its broad use as a chemotherapy agent. The development of effective and non-invasive strategies to prevent DOX-associated adverse cardiac events is urgently needed. We aimed to examine whether and how low-intensity pulsed ultrasound (LIPUS) plays a protective role in DOX-induced cardiotoxicity. Male C57BL/6J mice were used to establish models of both acute and chronic DOX-induced cardiomyopathy. Non-invasive LIPUS therapy was conducted for four consecutive days after DOX administration. Cardiac contractile function was evaluated by echocardiography. Myocardial apoptosis, oxidative stress, and fibrosis were analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining, dihydroethidium (DHE) staining, and picrosirius red staining assays. RNA-seq analysis was performed to unbiasedly explore the possible downstream regulatory mechanisms. Neutrophil recruitment and infiltration in the heart were analyzed by flow cytometry. The S100a8/a9 inhibitor ABR-238901 was utilized to identify the effect of S100a8/a9 signaling. We found that LIPUS therapy elicited a great benefit on DOX-induced heart contractile dysfunction in both acute and chronic DOX models. Chronic DOX administration increased serum creatine kinase and lactate dehydrogenase levels, as well as myocardial apoptosis, all of which were significantly mitigated by LIPUS. In addition, LIPUS treatment prevented chronic DOX-induced cardiac oxidative stress and fibrosis. RNA-seq analysis revealed that LIPUS treatment partially reversed alterations of gene expression induced by DOX. Gene ontology (GO) analysis of the downregulated genes between DOX-LIPUS and DOX-Sham groups indicated that inhibition of neutrophil chemotaxis might be involved in the protective effects of LIPUS therapy. Flow cytometry analysis illustrated the inhibitory effects of LIPUS on DOX-induced neutrophil recruitment and infiltration in the heart. Moreover, S100 calcium binding protein A8/A9 (S100a8/a9) was identified as a potential key target of LIPUS therapy. S100a8/a9 inhibition by ABR-238901 showed a similar heart protective effect against DOX-induced cardiomyopathy to LIPUS treatment. LIPUS therapy prevents DOX-induced cardiotoxicity through inhibition of S100a8/a9-mediated neutrophil recruitment to the heart, suggesting its potential application in cancer patients undergoing chemotherapy with DOX.

Effect of BRAF mutation on the prognosis for patients with colorectal cancer undergoing cytoreductive surgery for synchronous peritoneal metastasis.

Background: KRAS/BRAF mutations (mutKRAS/mutBRAF) are unfavorable prognostic factors for colorectal cancer (CRC) metastases to the liver and lungs. However, their effects on the prognosis for patients with synchronous peritoneal metastasis (S-PM) of CRC after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are controversial. In the study, we aimed to determine the effects of mutKRAS/mutBRAF on the prognosis for patients with S-PM who received CRS. Methods: A total of 142 patients diagnosed with S-PM between July 2007 and July 2019 were included in this study. The demographics, mutKRAS/mutBRAF status, overall survival (OS), and progression-free survival (PFS) of the patients were evaluated. The Kaplan-Meier method and log-rank test were used to estimate the difference in survival between groups. Results: Among 142 patients, 68 (47.9%) showed mutKRAS and 42 (29.5%) showed mutBRAF. The median OS values were 8.4 and 34.3 months for patients with mutBRAF and BRAF wild-type, respectively (P < 0.01). However, KRAS status was not significantly associated with median OS (P = 0.76). Multivariate analysis revealed carcinoembryonic antigen, CRS, HIPEC, and mutBRAF as independent predictors for OS. Based on these findings, a nomogram was constructed. The C-index was 0.789 (95% confidence interval, 0.742-0.836), indicating good predictive ability of the model. Furthermore, the 1- and 2-year survival calibration plots showed good agreement between the predicted and actual OS rates. The area under curves of the 1- and 2-year survival predictions based on the nomogram were 0.807 and 0.682, respectively. Additionally, mutBRAF was significantly associated with lower PFS (P < 0.001). Conclusions: mutBRAF is an independent prognostic risk factor for S-PM. The established nomogram predicted the OS of patients with CRC having S-PM with high accuracy, indicating its usefulness as a valuable prognostic tool for the designated patient cohort.

Simulation of dynamic monitoring for intracerebral hemorrhage based on magnetic induction phase shift technology.

Intracerebral hemorrhage (ICH) is a common and severe brain disease associated with high mortality and morbidity. Accurate measurement of the ICH area is an essential indicator for doctors to determine whether a surgical operation is necessary. However, although currently used clinical detection methods, such as computed tomography (CT) and magnetic resonance imaging (MRI), provide high-quality images, they may have limitations such as high costs, large equipment size, and radiation exposure to the human body in the case of CT. It makes long-term bedside monitoring infeasible. This paper presents a dynamic monitoring method for ICH areas based on magnetic induction. This study investigates the influence of the bleeding area and the position of ICH on the phase difference at the detection point near the area to be measured. The study applies a neural network algorithm to predict the bleeding area using the phase difference data received by the detection coil as the network input and the bleeding area as the network output. The relative error between the predicted and actual values of the neural network is calculated, and the error of each group of data is less than 4%, which confirms the feasibility of this method for detecting and even trend monitoring of the ICH area.

Pre-Protection and Mechanism of Crude Extracts from Dioscorea alata L. on H2O2-Induced IPEC-J2 Cells Oxidative Damage.

The purple tubers of Dioscorea alata L. have been found to contain a variety of bioactive chemical components, including anthocyanins, which make it significant to investigate the pre-protective effects of Dioscorea alata L. and its crude extracts on cells prior to oxidative stress. To establish a suitable oxidative damage model, an injured model of IPEC-J2 cells was created using H2O2 as the oxidant. Specifically, when the concentration of H2O2 was 120 µmol/L and the injured time was 8 h, the survival rate of cells decreased to approximately 70%, and the cells exhibited a noticeable oxidative stress reaction. Moreover, the crude extracts of Dioscorea alata L. demonstrated beneficial pre-protective effects on IPEC-J2 cells by increasing the total antioxidant capacity (T-AOC) and catalase (CAT) activities, augmenting the expression of total superoxide dismutase (T-SOD) and its genes, reducing the content of malondialdehyde (MDA) and the activity of glutathione peroxidase (GSH-PX) and its expression of genes, and promoting the expression of glucose transporter SGLT1 gene while reducing that of GULT2 gene, thereby facilitating the entry of anthocyanins into cells. In addition, the 50 µg/mL crude extracts effectively inhibited the phosphorylation of IκB and the p65 protein, thus reducing cellular oxidative stress. Given these findings, Dioscorea alata L. can be considered a natural antioxidant for practical breeding and production purposes, with an optimal concentration of crude extracts in this experiment being 50 µg/mL.

The largest and heaviest giant juvenile fibroadenoma of the breast in the Chinese population: A case report.

RATIONALE: Fibroadenoma is the most common benign tumor of the breast, but giant juvenile fibroadenoma exceeding 20 cm is much rare. This report presents the largest and heaviest giant juvenile fibroadenoma in an 18-year-old Chinese girl. DIAGNOSIS AND INTERVENTIONS: An 18-year-old adolescent girl with a 2-year history of a large left breast mass with progressive expansion over 11 months. A 28 × 21 cm soft swelling occupied the entire outer quadrants of the left breast. The huge mass sagged below the belly button, resulting in high asymmetry of the shoulders. Contralateral breast examination results were normal except for hypopigmentary detected on the nipple-areola complex. Under general anesthesia, the lump was completely excised along the outer envelope of the tumor, while reserving excessive resection of the skin. The patient's postoperative recovery was uneventful, and the surgical wound healed well. OUTCOMES: A radial incision operation was finally performed to remove the huge mass and to preserve the normal breast tissue and the nipple-areolar complex, not only considering the aesthetics but also preserving the ability to lactate. LESSONS: Currently, there is a lack of clear guidelines regarding the diagnostic and treatment modalities for a giant juvenile fibroadenoma. The principle of surgical choice is to balance aesthetics and function preservation.

Exploring differences in level of construction innovation: an empirical analysis in China.

Innovations can overcome constraints posed by resource depletion, increasing environmental and ecological protection concerns. There is considerable amount of innovation that occurs in the construction industry. Accordingly, construction innovation is receiving increasing attention in China. However, the provincial development level of construction innovation remains unclear. To address this gap, the present study employs data-driven measurement for the level of construction innovation. A total of 25 alternative indexes were selected based on the innovation ecosystem theory. Then, text preprocessing, statistical methods, and search statistics were employed to acquire index data. The indexes weights were determined through expert scoring and a cloud model. The quantitative measurement of the level of construction innovation was finally performed. Additionally, the exploratory results were revealed with the analyses of the overall, regional, and cluster. The results revealed that overall level of construction innovation in China is not high and regional distribution is uneven. Simultaneously, the level of construction innovation is consistent with local economic strength, and it is most sensitive to innovation output in regional level. Moreover, the spatial distribution of the level of construction innovation in China was showed, which has similarity with the characteristics of geographical location. The measurement system this study represents breakthroughs over traditional methods that rely on statistics, cases, or questionnaires, which can be applied to other research fields.

The Effect of Anthocyanins from Dioscorea alata L. on Antioxidant Properties of Perinatal Hainan Black Goats and Its Possible Mechanism in the Mammary Gland.

(1) Background: The mammary glands of the perinatal goats are susceptible to reactive oxygen species (ROS) leading to oxidative injury. Although Dioscorea alata L. is rich in anthocyanins with high safety and excellent free-radical-scavenging ability, the effect and mechanism of Dioscorea alata L. anthocyanins (DAC) on the antioxidant capacity of the black Hainan goat has been the subject of few studies to date; (2) Methods: For this reason, feeding experiments were performed by feeding experimental diets, and the pre-protective capacity of DAC on goat mammary epithelial cells was explored on the basis of the established model of H2O2 injury; (3) Results: As well as altering rumen fermentation parameters in perinatal female goats, dietary challenge also improves antioxidant capacity in their blood and milk. thereby enhancing children's antioxidant capacity and increasing their resistance to oxidative stress. However, we also found that DAC pretreatment was capable of activating both Nrf2 and MAPK/JNK pathways, which results in enhanced antioxidase activity and elimination of ROS; (4) Conclusions: Together, these findings suggest that DAC may have a pre-protective role on perinatal Hainan black goats through the regulation of Nrf2 and MAPK/JNK pathways in GMEC.

Hyperthermic intraperitoneal chemotherapy following up-front cytoreductive surgery versus cytoreductive surgery alone for isolated synchronous colorectal peritoneal metastases: A retrospective, observational study.

Background: To date, the value of hyperthermic intraperitoneal chemotherapy (HIPEC) following up-front resection for isolated synchronous colorectal peritoneal metastases seems controversial. Patients and Methods: This retrospective cohort study was conducted from September 1, 2012, to September 1, 2019, at a tertiary medical center in China. Patients with isolated synchronous colorectal peritoneal metastases were included in CRS plus HIPEC group or CRS alone group based on the treatment history. Overall survival and relapse-free survival were estimated using Cox proportional hazards regression analysis and Kaplan-Meier method. Results: 78 patients with isolated synchronous colorectal peritoneal metastases were identified among 396 patients with synchronous colorectal peritoneal metastases. 43 were in the cytoreductive surgery plus HIPEC group and 35 were in the cytoreductive surgery alone group. Among them, 61 patients had relapse-free survival data. The median peritoneal cancer index was 4 in all patients. After a median follow-up of 46.0 months, 5-year overall survival was 66.8% and the median relapse-free survival was 36.0 (95% CI, 6.8-65.1) months in the CRS plus HIPEC group. 5-year overall survival was 31.2% and the median relapse-free survival was 12.0 (95% CI, 9.0-15.0) months in the CRS alone group. Cox regression analyses showed that HIPEC was the independent prognostic factor for overall survival (P = 0.004) and relapse-free survival (P = 0.049). Conclusion: Findings of the present study suggest that HIPEC following up-front CRS could improve overall survival and relapse-free survival in patients with isolated synchronous colorectal peritoneal metastases.

A Prediction Model Intended for Exploratory Laparoscopy Risk Stratification in Colorectal Cancer Patients With Potential Occult Peritoneal Metastasis.

Background: The early diagnosis of occult peritoneal metastasis (PM) remains a challenge due to the low sensitivity on computed tomography (CT) images. Exploratory laparoscopy is the gold standard to confirm PM but should only be proposed in selected patients due to its invasiveness, high cost, and port-site metastasis risk. In this study, we aimed to develop an individualized prediction model to identify occult PM status and determine optimal candidates for exploratory laparoscopy. Method: A total of 622 colorectal cancer (CRC) patients from 2 centers were divided into training and external validation cohorts. All patients' PM status was first detected as negative on CT imaging but later confirmed by exploratory laparoscopy. Multivariate analysis was used to identify independent predictors, which were used to build a prediction model for identifying occult PM in CRC. The concordance index (C-index), calibration plot and decision curve analysis were used to evaluate its predictive accuracy and clinical utility. Results: The C-indices of the model in the development and validation groups were 0.850 (95% CI 0.815-0.885) and 0.794 (95% CI, 0.690-0.899), respectively. The calibration curve showed consistency between the observed and predicted probabilities. The decision curve analysis indicated that the prediction model has a great clinical value between thresholds of 0.10 and 0.72. At a risk threshold of 30%, a total of 40% of exploratory laparoscopies could have been prevented, while still identifying 76.7% of clinically occult PM cases. A dynamic online platform was also developed to facilitate the usage of the proposed model. Conclusions: Our individualized risk model could reduce the number of unnecessary exploratory laparoscopies while maintaining a high rate of diagnosis of clinically occult PM. These results warrant further validation in prospective studies. Clinical Trial Registration: https://www.isrctn.com, identifier ISRCTN76852032.

Risk Factors for Synchronous Peritoneal Metastases in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Background: Early detection of synchronous colorectal peritoneal metastases (CPMs) is difficult due to the absence of typical symptoms and the low accuracy of imaging examinations. Increasing the knowledge of the risk factors for synchronous CPM may be essential for early diagnosis and improving their management. This study aimed to identify the risk factors for synchronous CPM. Method: The study was registered at PROSPERO (CRD42020198548). The PubMed, Embase and Cochrane Library databases were searched for studies comparing the clinicopathological and molecular features between patients with or without synchronous CPM. The pooled data were assessed by a random-effects model. Results: Twenty-five studies were included. A synchronous CPM was positively associated with female sex (OR 1.299; 1.118 to 1.509; P = 0.001), PROK1/PROKR2-positivity (OR 2.244; 1.031 to 4.884; P = 0.042), right-sided colon cancer (OR 2.468; 2.050 to 2.970; P < 0.001), poorly differentiated grade (OR 2.560; 1.537 to 4.265; P < 0.001), BRAF mutation (OR 2.586; 1.674 to 3.994; P < 0.001), mucinous adenocarcinoma (OR 3.565; 2.095 to 6.064; P < 0.001), signet-ring cell carcinoma (OR 4.480; 1.836 to 10.933; P = 0.001), N1-2 (OR 5.665; 3.628 to 8.848; P < 0.001), T4 (OR 12.331; 7.734 to 19.660; P < 0.001) and elevated serum CA19-9 (OR 12.868; 5.196 to 31.867; P < 0.001). Conclusions: These evidence-based risk factors are indicators that could predict the presence of synchronous CPMs and can improve their management. Systematic Review Registration: www.crd.york.ac.uk/prospero, identifier: CRD42020198548.

Comprehensive Analysis of Microsatellite-Related Transcriptomic Signature and Identify Its Clinical Value in Colon Cancer.

Background: Microsatellite has been proved to be an important prognostic factor and a treatment reference in colon cancer. The transcriptome profile and tumor microenvironment of different microsatellite statuses are different. Metastatic colon cancer patients with microsatellite instability-high (MSI-H) are sensitive to immune checkpoint inhibitors (ICIs), but not fluorouracil. Efforts have been devoted to identify the predictive factors of immunotherapy. Methods: We analyzed the transcriptome profile of different microsatellite statuses in colon cancer by using single-cell and bulk transcriptome data from publicly available databases. The immune cells in the tumor microenvironment were analyzed by the ESTIMATION algorithm. The microsatellite-related gene signature (MSRS) was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression based on the differentially expressed genes (DEGs) and its prognostic value and predictive value of response to immunotherapy were assessed. The prognostic value of the MSRS was also validated in another cohort. Results: The MSI-H cancers cells were clustered differentially in the dimension reduction plot. Most of the immune cells have a higher proportion in the tumor immune microenvironment, except for CD56 bright natural killer cells. A total of 238 DEGs were identified. Based on the 238 DEGs, a neural network was constructed with a Kappa coefficient of 0.706 in the testing cohort. The MSRS is a favorable prognostic factor of overall survival, which was also validated in another cohort (GSE39582). Besides, MSRS is correlated with tumor mutation burden in MSI-H colon cancer. However, the MSRS is a barely satisfactory factor in predicting immunotherapy with the area under the curve (AUC) of 0.624. Conclusion: We developed the MSRS, which is a robust prognostic factor of overall survival in spite of a barely satisfactory immunotherapy predictor. Further studies may need to improve the predictive ability.

Residues of Culinary-Medicinal Winter Mushroom, Flammulina velutipes (Agaricomycetes), Cultivation as a Potential Source of Functional Skin Substitute with Multiple Bioactivities.

Residues generated during the cultivation of edible mushroom Flammulina velutipes are abundant and utilized with low efficiency. In this study, the composition and bioactivities of a skin substitute named TG05 obtained from residues of the F. velutipes cultivation process were investigated. The main composition of TG05 was considered to be chitin and it inhibited growth of Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. TG05 also suppressed the inflammatory response through the inducible nitric oxide synthase signaling pathway. Inflammation was attenuated by reducing the expression of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and prostaglandin E2 at the transcription level. Furthermore, TG05 exhibited antioxidant activities based on hydroxyl, 2,2-diphenyl-1-picryl-hydrazy, 2,2'-azobis-(3-ethylbenzothiazoline-6-sulfonic acid), superoxide anion radical scavenging activity, and reducing power assays. However, the effect of TG05 was independent of hyaluronidase inhibitory activity. Taken together, specific mechanisms related to the notable wound-healing-promoting activity of TG05 were demonstrated, mainly attributable to its antimicrobial, anti-inflammatory, and antioxidant activities. Therefore, TG05 may have potential for use as a functional biomaterial in various applications.

Hypoglycemia-Exacerbated Mitochondrial Connexin 43 Accumulation Aggravates Cardiac Dysfunction in Diabetic Cardiomyopathy.

Background: Diabetic cardiomyopathy (DCM) is a complex multifaceted disease responsible for elevated heart failure (HF) morbidity and mortality in patients with diabetes mellitus (DM). Patients with DCM exhibit subclinical diastolic dysfunction, progression toward systolic impairment, and abnormal electrophysiology. Hypoglycemia events that occur spontaneously or due to excess insulin administration threaten the lives of patients with DM-with the increased risk of sudden death. However, the molecular underpinnings of this fatal disease remain to be elucidated. Methods and Results: Here, we used the established streptozotocin-induced DCM murine model to investigate how hypoglycemia aggravates DCM progression. We confirmed connexin 43 (Cx43) dissociation from cell-cell interaction and accumulation at mitochondrial inner membrane both in the cardiomyocytes of patients with DM and DCM murine. Here, we observed that cardiac diastolic function, induced by chronic hyperglycemia, was further aggravated upon hypoglycemia challenge. Similar contractile defects were recapitulated using neonatal mouse ventricular myocytes (NMVMs) under glucose fluctuation challenges. Using immunoprecipitation mass spectrometry, we identified and validated that hypoglycemia challenge activates the mitogen-activated protein kinase kinase (MAPK kinase) (MEK)/extracellular regulated protein kinase (ERK) and inhibits phosphoinositide 3-kinase (PI3K)/Akt pathways, which results in Cx43 phosphorylation by Src protein and translocation to mitochondria in cardiomyocytes. To determine causality, we overexpressed a mitochondrial targeting Cx43 (mtCx43) using adeno-associated virus serotype 2 (AAV2)/9. At normal blood glucose levels, mtCx43 overexpression recapitulated cardiac diastolic dysfunction as well as aberrant electrophysiology in vivo. Our findings give support for therapeutic targeting of MEK/ERK/Src and PI3K/Akt/Src pathways to prevent mtCx43-driven DCM. Conclusion: DCM presents compensatory adaptation of mild mtCx43 accumulation, yet acute hypoglycemia challenges result in further accumulation of mtCx43 through the MEK/ERK/Src and PI3K/Akt/Src pathways. We provide evidence that Cx43 mislocalization is present in hearts of patients with DM hearts, STZ-induced DCM murine model, and glucose fluctuation challenged NMVMs. Mechanistically, we demonstrated that mtCx43 is responsible for inducing aberrant contraction and disrupts electrophysiology in cardiomyocytes and our results support targeting of mtCx43 in treating DCM.

Muscle-inspired MXene/PVA hydrogel with high toughness and photothermal therapy for promoting bacteria-infected wound healing.

The process of wound healing is often accompanied by bacterial infection, which is a serious threat to human health. The abuse of antibiotics in traditional therapy aggravates the resistance of bacteria and gradually reduces the therapeutic effect. Therefore, it is important to develop effective antibacterial dressings to promote wound healing and prevent infection. Photothermal therapy (PTT) is considered a quick and reliable method of suppressing bacterial infections without developing drug resistance. The unique network structure and high water retention of hydrogel help wound healing. Inspired by the hierarchical assembly of anisotropic structures across multiple length scales of muscles, herein a directional freezing-assisted salting-out method was used to prepare anisotropic MXene@PVA hydrogels. The hydrogel not only had excellent mechanical properties (stress up to 0.5 MPa and strain up to 800%), but could also be used for local hyperthermia of infected sites using an NIR laser (808 nm). Owing to the excellent photothermal properties of MXene, its main antibacterial mechanism is hyperthermia and the hydrogel showed broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria (inhibition rates of Escherichia coli and Staphylococcus aureus were 98.3 and 95.5% respectively). In addition, it could effectively promote the proliferation of NIH-3T3 cells. In mouse wound models, the hydrogel was effective in inhibiting wound infection and promoting skin wound healing (the rate of wound closure was 98%). These results indicated that the MXene@PVA hydrogel, with high toughness and anisotropy properties, has the potential to be an excellent antibacterial wound healing dressing.