Exosomes derived from umbilical cord-derived mesenchymal stem cells exposed to diabetic microenvironment enhance M2 macrophage polarization and protect against diabetic nephropathy.

The role of mesenchymal-stem-cell-derived exosomes (MSCs-Exo) in the regulation of macrophage polarization has been recognized in several diseases. There is emerging evidence that MSCs-Exo partially prevent the progression of diabetic nephropathy (DN). This study aimed to investigate whether exosomes secreted by MSCs pre-treated with a diabetic environment (Exo-pre) have a more pronounced protective effect against DN by regulating the balance of macrophages. Exo-pre and Exo-Con were isolated from the culture medium of UC-MSCs pre-treated with a diabetic mimic environment and natural UC-MSCs, respectively. Exo-pre and Exo-Con were injected into the tail veins of db/db mice three times a week for 6 weeks. Serum creatinine and serum urea nitrogen levels, the urinary protein/creatinine ratio, and histological staining were used to determine renal function and morphology. Macrophage phenotypes were analyzed by immunofluorescence, western blotting, and quantitative reverse transcription polymerase chain reaction. In vitro, lipopolysaccharide-induced M1 macrophages were incubated separately with Exo-Con and Exo-pre. We performed microRNA (miRNA) sequencing to identify candidate miRNAs and predict their target genes. An miRNA inhibitor was used to confirm the role of miRNAs in macrophage modulation. Exo-pre were more potent than Exo-Con at alleviating DN. Exo-pre administration significantly reduced the number of M1 macrophages and increased the number of M2 macrophages in the kidney compared to Exo-Con administration. Parallel outcomes were observed in the co-culture experiments. Moreover, miR-486-5p was distinctly expressed in Exo-Con and Exo-pre groups, and it played an important role in macrophage polarization by targeting PIK3R1 through the PI3K/Akt pathway. Reducing miR-486-5p levels in Exo-pre abolished macrophage polarization modulation. Exo-pre administration exhibited a superior effect on DN by remodeling the macrophage balance by shuttling miR-486-5p, which targets PIK3R1.

Non-target discovery and risk prediction of per- and polyfluoroalkyl substances (PFAS) and transformation products in wastewater treatment systems.

Wastewater treatment plants (WWTPs) serve as the main destination of many wastes containing per- and polyfluoroalkyl substances (PFAS). Here, we investigated the occurrence and transformation of PFAS and their transformation products (TPs) in wastewater treatment systems using high-resolution mass spectrometry-based target, suspect, and non-target screening approaches. The results revealed the presence of 896 PFAS and TPs in aqueous and sludge phases, of which 687 were assigned confidence levels 1-3 (46 PFAS and 641 TPs). Cyp450 metabolism and environmental microbial degradation were found to be the primary metabolic transformation pathways for PFAS within WWTPs. An estimated 52.3 %, 89.5 %, and 13.6 % of TPs were believed to exhibit persistence, bioaccumulation, and toxicity effects, respectively, with a substantial number of TPs posing potential health risks. Notably, the length of the fluorinated carbon chain in PFAS and TPs was likely associated with increased hazard, primarily due to the influence of biodegradability. Ultimately, two high riskcompounds were identified in the effluent, including one PFAS (Perfluorobutane sulfonic acid) and one enzymatically metabolized TP (23-(Perfluorobutyl)tricosanoic acid@BTM0024_cyp450). It is noteworthy that the toxicity of some TPs exceeded that of their parent compounds. The results from this study underscores the importance of PFAS TPs and associated environmental risks.

Metagenomic investigation of antibiotic resistance genes and resistant bacteria contamination in pharmaceutical plant sites in China.

Pharmaceutical plant sites play a significant role in the dissemination of antibiotic resistance genes (ARGs) into the environment. It is imperative to comprehensively monitor of ARGs across various environmental media at these sites. This study focused on three pharmaceutical plants, two located in North China and one in South China. Through metagenomic approaches, we examined the composition, mobility potential, and bacterial hosts of ARGs in diverse media such as process water, groundwater, topsoil, soil cores, and pharmaceutical fermentation residues across diverse environmental matrices, including topsoil, soil cores, process water, groundwater, and pharmaceutical fermentation residues. We identified a wide array of ARGs, comprising 21 types and 740 subtypes, with process water exhibiting the highest abundance and diversity. Treatment processes varied in their efficacy in eliminating ARGs, and the clinically relevant ARGs should also be considered when evaluating wastewater treatment plant efficiency. Geographical distinctions in groundwater ARG distribution between northern and southern regions were observed. Soil samples from the three sites showed minimal impact from pharmaceutical activity, with vancomycin-resistance genes being the most prevalent. High levels of ARGs in pharmaceutical fermentation residues underscore the necessity for improved waste management practices. Metagenomic assembly revealed that plasmid-mediated ARGs were more abundant than chromosome-mediated ARGs. Metagenome-assembled genomes (MAGs) analysis identified 166 MAGs, with 62 harboring multiple ARGs. Certain bacteria tended to carry specific types of ARGs, revealing distinct host-resistance associations. This study enhances our understanding of ARG dissemination across different environmental media within pharmaceutical plants and underscores the importance of implementing strict regulations for effluent and residue discharge to control ARG spread.

Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting Kv1.2 Channel.

Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences  is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

Molecular engineering of metal-based photosensitizers with narrow band gap for efficient photodynamic therapy.

Three iridium(III) complexes were designed with the purpose of elucidating the photo-physicochemical properties of iridium(III) complexes with narrow band gap at the electronic level. This study indicates that increasing the ligand rigidity and electron delocalization of the compounds can suppress the ring-stretching vibrations of the iridium(III) complex, thus improving their photo-chemical activity and photocytotoxicity.

Synthesis of 6/5/3-Fused Tricyclic Scaffolds via Multistep Cascade Cyclization of α-Aryl Vinylsulfoniums with para-Quinamines and para-Quinols.

Herein, we present a straightforward approach to access hydroindoline-5-one-based 6/5/3-fused polycyclic ring structures through multistep cascade reactions involving α-aryl vinylsulfoniums and para-quinamines. The reactions proceed smoothly under mild conditions to deliver the desired products in generally good isolated yields. This protocol is also applicable to the cascade cycloaddition reactions of α-aryl vinylsulfoniums and para-quinols, effectively generating complex tricyclic scaffolds. In addition, the scale-up synthesis and further derivatizations demonstrate the potential synthetic application of the protocol.

Comparison of the repeatability and reproducibility of corneal thickness mapping using optical coherence tomography according to tear film break-up time.

BACKGROUND: To compare the repeatability and reproducibility of corneal and corneal epithelial thickness mapping using anterior segment optical coherence tomography (AS-OCT) according to tear film break-up time (TBUT). METHODS: The included eyes were divided into three subgroups according to TBUT (group 1: TBUT ≤ 5 s, group 2: 5 s < TBUT ≤ 10 s, and group 3: TBUT > 10 s). All eyes were imaged separately thrice by two operators to obtain the thickness maps (TMs) of the cornea and corneal epithelium based on spatial zones encompassing a 9-mm-diameter area. Each TM consisted of 25 areas. Intraoperator (repeatability) and interoperator (reproducibility) standard deviations (Sws), coefficients of variation (CoVs), and intraclass correlation coefficients (ICCs) among the tests were calculated and compared in all the areas. RESULTS: Altogether, 132 eyes of 67 subjects were included (50, 47, and 35 eyes in groups 1, 2, and 3; respectively). The ICCs of corneal epithelial thickness and corneal thickness were > 0.75 in most of the areas. Pairwise comparisons showed that AS-OCT exhibited lower repeatability in group 1 than in groups 2 and 3 (P < 0.05). However groups 2 and 3 showed similar results. Sws and CoVs of corneal epithelial thickness exhibited no significant interoperator differences. While no significant differences were observed in corneal thickness in most of the areas. CONCLUSIONS: TBUT significantly influences the repeatability of corneal and corneal epithelial thickness measurements. Poor tear film stability requires careful evaluation of corneal epithelial thickness.

Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis.

Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.

A high hydrophobic moment arginine-rich peptide screened by a machine learning algorithm enhanced ADC antitumor activity.

Cell-penetrating peptides (CPPs) with better biomolecule delivery properties will expand their clinical applications. Using the MLCPP2.0 machine algorithm, we screened multiple candidate sequences with potential cellular uptake ability from the nuclear localization signal/nuclear export signal database and verified them through cell-penetrating fluorescent tracing experiments. A peptide (NCR) derived from the Rev protein of the caprine arthritis-encephalitis virus exhibited efficient cell-penetrating activity, delivering over four times more EGFP than the classical CPP TAT, allowing it to accumulate in lysosomes. Structural and property analysis revealed that a high hydrophobic moment and an appropriate hydrophobic region contribute to the high delivery activity of NCR. Trastuzumab emtansine (T-DM1), a HER2-targeted antibody-drug conjugate, could improve its anti-tumor activity by enhancing targeted delivery efficiency and increasing lysosomal drug delivery. This study designed a new NCR vector to non-covalently bind T-DM1 by fusing domain Z, which can specifically bind to the Fc region of immunoglobulin G and effectively deliver T-DM1 to lysosomes. MTT results showed that the domain Z-NCR vector significantly enhanced the cytotoxicity of T-DM1 against HER2-positive tumor cells while maintaining drug specificity. Our results make a useful attempt to explore the potential application of CPP as a lysosome-targeted delivery tool.

The surgical strategy "CSF decompression" facilitates outcomes of adults with Chiari malformation type I: An observational, real-world, single center study of 528 patients.

OBJECTIVES: We designed this study to introduce the surgical strategy "CSF decompression" in treating Chiari malformation type I (CMI), and compared the "CSF decompression" strategy with other surgical strategies to provide a solid basis for patient counseling. METHODS: A total of 528 consecutive CMI patients who underwent surgical interventions from 2012 to 2022 were enrolled. The surgical strategy for these patients was bony and dural decompression (BDD), anatomical reduction of herniated tonsils (AR) or CSF decompression (CSFD). Short-term results were determined after 3 months; long-term outcomes were evaluated at last follow-up and at least 18 months. RESULTS: The CSFD strategy was independently associated with better long- or short-term primary outcomes than AR or BDD (P < 0.001). Compared with short-term, the long-term outcomes were better in CSFD patients (P = 0.035), but were worse in BDD patients (P = 0.03). Specific surgical techniques cannot affect the long- and short-term outcomes of CMI patients. CSFD provided better long-term syringomyelia improvement than short-term (181/218, 83% vs 169/218, 77.5%; P < 0.001). CONCLUSION: The "CSF decompression" surgical strategy, but not a specific surgical technique or operative method, was associated with favorable neurological outcomes in adult CMI patients. The surgical technique and operative method should be selected according to the characteristics of each patient and the intraoperative condition to normalized CSF circulation at CVJ. The intraoperative target maybe smoothly CSF flow, out from the fourth ventricle and in to the bilateral Luschka foramina, could be observed.

Purine metabolite inosine induced by transforming growth factor­ß promotes epithelial­mesenchymal transition in colorectal cancer.

Transforming growth factor-ß (TGF-ß) signaling pathway serves a pivotal role in the pathogenesis of colorectal cancer (CRC). However, the specific molecular mechanisms by which the TGF-ß signaling pathway regulates CRC are still not fully understood. In the present study, metabolomics and transcriptomics were used to screen for key metabolites and regulatory genes most related to the regulation of the TGF-ß signaling pathway in CRC. Additionally, reverse transcription-quantitative PCR, western blotting and Transwell assays were performed to assess the process of epithelial-mesenchymal transition (EMT). Metabolomics analysis indicated that TGF-ß1 has an impact on purine metabolism, leading to an increase in the purine metabolite inosine. The increase of inosine is essential for facilitating EMT and cell migration in CRC cells. Furthermore, the integrated analysis of metabolomics and transcriptomics data revealed that TGF-ß1 induces the expression of laccase domain-containing 1 (LACC1), an enzyme involved in the regulation of inosine. Knockdown of LACC1 resulted in a reduction of TGF-ß1-induced alterations in inosine levels, EMT and cell migration in CRC cells. The results of the present study suggest that the TGF-ß signaling pathway is involved in the regulation of purine metabolism in CRC through the modulation of LACC1 expression. Furthermore, LACC1 appears to influence EMT and cell migration by elevating the levels of the purine metabolite inosine.

A coupling strategy combined with acid-hydrothermal and novel DES pretreatment: Enhancing biomethane yield under solid-state anaerobic digestion and efficiently producing xylo-oligosaccharides and recovered lignin from poplar waste.

Lignocellulose is an abundant renewable bio-macromolecular complex, which can be used to produce biomethane and other high-value products. The lignin, presents in lignocellulose is typically regarded as an inhibitor of anaerobic digestion. Therefore, it is crucial to develop a novel selective separation strategy to achieve efficient biomethane production and all-component utilization of biomass. Hence, a combination of two-step pretreatment and solid-state anaerobic digestion was employed to enhance the production of biomethane and to generate valuable chemicals from poplar waste. Optimal conditions (4 % acetic acid, 170 °C, and 40 min) resulted in 70.85 % xylan removal, yielding 50.28 % xylo-oligosaccharides. The effect of a strong acid 4-CSA-based novel three-constituent DES on delignification was investigated from 80 °C to 100 °C; the cellulose content of DES pretreated poplar increased from 64.11 % to 80.92 %, and the delignification rate increased from 49.0 % to 90.4 %. However, high delignification of the pretreated poplar (DES-100 and DES-110) led to a rapid accumulation of volatile organic acids during the hydrolysis and acidogenesis stages, resulting in methanogenesis inhibition. The highest biomethane yield of 208 L/kg VS was achieved with DES-80 (49.0 % delignification), representing a 148 % improvement compared over untreated poplar. This approach demonstrates the potential for comprehensive utilization of all components of biomass waste.

FUS3: Orchestrating soybean plant development and boosting stress tolerance through metabolic pathway regulation.

Soybean research has gained immense attention due to its extensive use in food, feedstock, and various industrial applications, such as the production of lubricants and engine oils. In oil crops, the process of seed development and storage substances accumulation is intricate and regulated by multiple transcription factors (TFs). In this study, FUSCA3 (GmFUS3) was characterized for its roles in plant development, lipid metabolism, and stress regulation. Expressing GmFUS3 in atfus3 plants restored normal characteristics observed in wild-type plants, including cotyledon morphology, seed shape, leaf structure, and flower development. Additionally, its expression led to a significant increase of 25% triacylglycerols (TAG) and 33% in protein levels. Transcriptomic analysis further supported the involvement of GmFUS3 in various phases of plant development, lipid biosynthesis, lipid trafficking, and flavonoid biosynthesis. To assess the impact of stress on GmFUS3 expression, soybean plants were subjected to different stress conditions, and the its expression was assessed. Transcriptomic data revealed significant alterations in the expression levels of approximately 80 genes linked to reactive oxygen species (ROS) signaling and 40 genes associated with both abiotic and biotic stresses. Additionally, GmFUS3 was found to regulate abscisic acid synthesis and interact with nucleoside diphosphate kinase 1, which is responsible for plant cellular processes, development, and stress response. Overall, this research sheds light on the multifaceted functions of GmFUS3 and its potential applications in enhancing crop productivity and stress tolerance.

Metabolic engineering for compartmentalized biosynthesis of the valuable compounds in Saccharomyces cerevisiae.

Saccharomyces cerevisiae is commonly used as a microbial cell factory to produce high-value compounds or bulk chemicals due to its genetic operability and suitable intracellular physiological environment. The current biosynthesis pathway for targeted products is primarily rewired in the cytosolic compartment. However, the related precursors, enzymes, and cofactors are frequently distributed in various subcellular compartments, which may limit targeted compounds biosynthesis. To overcome above mentioned limitations, the biosynthesis pathways are localized in different subcellular organelles for product biosynthesis. Subcellular compartmentalization in the production of targeted compounds offers several advantages, mainly relieving competition for precursors from side pathways, improving biosynthesis efficiency in confined spaces, and alleviating the cytotoxicity of certain hydrophobic products. In recent years, subcellular compartmentalization in targeted compound biosynthesis has received extensive attention and has met satisfactory expectations. In this review, we summarize the recent advances in the compartmentalized biosynthesis of the valuable compounds in S. cerevisiae, including terpenoids, sterols, alkaloids, organic acids, and fatty alcohols, etc. Additionally, we describe the characteristics and suitability of different organelles for specific compounds, based on the optimization of pathway reconstruction, cofactor supplementation, and the synthesis of key precursors (metabolites). Finally, we discuss the current challenges and strategies in the field of compartmentalized biosynthesis through subcellular engineering, which will facilitate the production of the complex valuable compounds and offer potential solutions to improve product specificity and productivity in industrial processes.

Anti-PD-(L)1-Based Neoadjuvant Therapy in Head and Neck Carcinoma: a Meta-analysis of Prospective Clinical Trials.

OBJECTIVE: This meta-analysis aims to evaluate the efficacy and safety of antiprogressive disease (PD)-(L)1-based neoadjuvant therapy in head and neck squamous cell carcinoma (HNSCC) patients and identify potential prognostic biomarkers. DATA SOURCES: Databases were systematically searched for prospective clinical trials evaluating the efficacy and safety of anti-PD-(L)1-based neoadjuvant therapy for HNSCC before January 12, 2024. REVIEW METHODS: We estimated the efficacy and safety of neoadjuvant immune checkpoint inhibitors. Subgroup and sensitivity analyses were further performed. RESULTS: A total of 570 patients from 20 studies were included. The pooled major pathological response (MPR), pathological complete response (pCR), and partial pathological response (PPR) rates were 30.7%, 15.3%, and 68.2%, respectively. Surgical complications, surgical delayed rate, all grade treatment-related adverse effects (TRAEs) and ≥Grade 3 TRAEs were 0.6%, 0.3%, 82.6%, and 9.7%, respectively. Best MPR or pCR rate was detected in patients receiving neoadjuvant anti-PD-(L)1 therapy + radiotherapy (with MPR rate of 75.5% and pCR rate of 51.1%) and neoadjuvant anti-PD-(L)1 therapy + chemotherapy groups (with MPR rate of 57.5% and pCR rate of 26.7%). No differences were detected in subgroups stratified by neoadjuvant treatment cycles, human papillomavirus (HPV) status, and tumor location. Patients with baseline Combined Positive Score (CPS) ≥ 20 have higher MPR and pCR rates compared to patients with CPS < 20. High Tumor Cell Proportion Score was also associated with MPR and pCR. Objective response rate is a strong predictor of MPR (odds ratio [OR] = 7.78, 95% confidence interval [CI] = 3.20%-18.91%) and pCR (OR = 3.24, 95% CI = 1.40%-7.48%). CONCLUSION: Anti-PD-(L)1-based neoadjuvant therapy was effective and safe for HNSCC patients.

Epidemiological Characteristics and Genotypic Features of Rotavirus and Norovirus in Jining City, 2021-2022.

Diarrhea, often caused by viruses like rotavirus (RV) and norovirus (NV), is a global health concern. This study focuses on RV and NV in Jining City from 2021 to 2022. Between 2021 and 2022, a total of 1052 diarrhea samples were collected. Real-Time Quantitative Fluorescent Reverse Transcriptase-PCR was used to detect RV-A, NV GI, and NV GII. For RV-A-positive samples, VP7 and VP4 genes were sequenced for genotype analysis, followed by the construction of evolutionary trees. Likewise, for NV-GII-positive samples, VP1 and RdRp genes were sequenced for genotypic analysis, and evolutionary trees were subsequently constructed. Between 2021 and 2022, Jining City showed varying detection ratios: RV-A alone (excluding co-infection of RV-A and NV GII) at 7.03%, NV GI at 0.10%, NV GII alone (excluding co-infection of RV-A and NV GII) at 5.42%, and co-infection of RV-A and NV GII at 1.14%. The highest RV-A ratios were shown in children ≤1 year and 2-5 years. Jining, Jinxiang County, and Liangshan County had notably high RV-A ratios at 24.37% (excluding co-infection of RV-A and NV GII) and 18.33% (excluding co-infection of RV-A and NV GII), respectively. Jining, Qufu, and Weishan had no RV-A positives. Weishan showed the highest NV GII ratios at 35.48% (excluding co-infection of RV-A and NV GII). Genotype analysis showed that, in 2021, G9P[8] and G2P[4] were dominant at 94.44% and 5.56%, respectively. In 2022, G8P[8], G9P[8], and G1P[8] were prominent at 75.86%, 13.79%, and 10.35%, respectively. In 2021, GII.3[P12], GII.4[P16], and GII.4[P31] constituted 71.42%, 14.29%, and 14.29%, respectively. In 2022, GII.3[P12] and GII.4[P16] accounted for 55.00% and 45.00%, respectively. RV-A and NV showed varying patterns for different time frames, age groups, and regions within Jining. Genotypic shifts were also observed in prevalent RV-A and NV GII strains in Jining City from 2021 to 2022. Ongoing monitoring of RV-A and NV is recommended for effective prevention and control.

Analysis of tumor microenvironment alterations in partially responsive rectal cancer patients treated with neoadjuvant chemoradiotherapy.

PURPOSE: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. METHODS: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. RESULTS: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and ß-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). CONCLUSIONS: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.

Hydrogel Wound Dressings Accelerating Healing Process of Wounds in Movable Parts.

Skin is the largest organ in the human body and requires proper dressing to facilitate healing after an injury. Wounds on movable parts, such as the elbow, knee, wrist, and neck, usually undergo delayed and inefficient healing due to frequent movements. To better accommodate movable wounds, a variety of functional hydrogels have been successfully developed and used as flexible wound dressings. On the one hand, the mechanical properties, such as adhesion, stretchability, and self-healing, make these hydrogels suitable for mobile wounds and promote the healing process; on the other hand, the bioactivities, such as antibacterial and antioxidant performance, could further accelerate the wound healing process. In this review, we focus on the recent advances in hydrogel-based movable wound dressings and propose the challenges and perspectives of such dressings.