Systematic review on marine carbon source-mannitol: Applications in synthetic biology.

Mannitol, one of the most widespread sugar alcohols, has been integral to daily human life for two centuries. Global population growth and competition for freshwater, food, and land have prompted a shift in the fermentation industry from terrestrial to marine raw materials. Mannitol is a readily available carbohydrate in brown seaweed from the ocean and possess a higher reducing power than glucose, making it a promising substrate for biological manufacturing. This has spurred numerous explorations into converting mannitol into high-value chemicals. Researchers have engineered microorganisms to utilize mannitol in various synthetic biological applications, including: (1) employing mannitol as an inducer to control the activation and deactivation of genetic circuits; (2) using mannitol as a carbon source for synthesizing high-value chemicals through biomanufacturing. This review summarizes the latest advances in the application of mannitol in synthetic biology. AIM OF REVIEW: The aim is to present a thorough and in-depth knowledge of mannitol, a marine carbon source, and then use this carbon source in synthetic biology to improve the competitiveness of biosynthetic processes. We outlined the methods and difficulties of utilizing mannitol in synthetic biology with a variety of microbes serving as hosts. Furthermore, future research directions that could alleviate the carbon catabolite repression (CCR) relationship between glucose and mannitol are also covered. EXPECTED CONTRIBUTIONS OF REVIEW: Provide an overview of the current state, drawbacks, and directions for future study on mannitol as a carbon source or genetic circuit inducer in synthetic biology.

Relightable Detailed Human Reconstruction from Sparse Flashlight Images.

We present a lightweight system for reconstructing human geometry and appearance from sparse flashlight images. Our system produces detailed geometry including garment wrinkles and surface reflectance, which are exportable for direct rendering and relighting in traditional graphics pipelines. By capturing multi-view flashlight images using a consumer camera equipped with an co-located LED (e.g., a cell phone), we obtain view-specific shading cues that aid in the determination of surface orientation and help disambiguate between shading and material. To enable the reconstruction of geometry and appearance from sparse-view flashlight images, we integrate a pre-trained model into a differentiable physics-based rendering framework. As the learned image features from synthetic data cannot accurately reflect the shading features on real images, which is crucial for the high-quality reconstruction of geometry details and appearance, we propose to jointly optimize the image feature extractor with two MLPs for SDF and BRDF prediction using the differentiable physics-based rendering. Compared with existing methods for relightable human reconstruction, our system is able to produce high-fidelity 3D human models with more accurate geometry and appearance under the same condition. Our code and data are available at http://github.com/Jarvisss/Relightable_human_recon.

Bone marrow adipogenic lineage precursors are the major regulator of bone resorption in adult mice.

Bone resorption by osteoclasts is a critical step in bone remodeling, a process important for maintaining bone homeostasis and repairing injured bone. We previously identified a bone marrow mesenchymal subpopulation, marrow adipogenic lineage precursors (MALPs), and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre . To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone, we generated inducible reporter mice ( Adipoq-CreER Tomato ) and RANKL deficient mice ( Adipoq-CreER RANKLflox/flox, iCKO ). Single cell-RNA sequencing data analysis, lineage tracing, and in situ hybridization revealed that Adipoq+ cells contain not only MALPs but also late mesenchymal progenitors capable of osteogenic differentiation. However, RANKL mRNA was only detected in MALPs, but not in osteogenic cells. RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae within 1 month due to diminished bone resorption but had no effect on the cortical bone. Ovariectomy (OVX) induced trabecular bone loss at both sites. RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass. Furthermore, bone healing after drill-hole injury was delayed in iCKO mice. Together, our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis, postmenopausal bone loss, and injury repair.

Well-Defined Homopolymer Nanoparticles with Uniaxial Molecular Orientation by Synchronized Polymerization and Self-Assembly.

Synthesizing anisotropic polymeric nanoparticles (NPs) with well-defined shapes, dimensions, and molecular orientations is a very challenging task. Herein, we report the synthesis of surprisingly highly uniform shape-anisotropic polymer NPs with uniaxial internal molecular orientation. Keys to our method are synchronized polymerization and self-assembly (SPSA), which can even be realized by regular dispersion polymerization. This is demonstrated using a monomer containing a rigid 4-nitroazobenzene (NAB) side group. The short nucleation period, the completion of microphase separation before molecular motion is frozen, and sufficient low particle/solvent interfacial tension are shown to be the origins of the highly uniform dimensions, single liquid crystal domains, and well-defined anisotropic shape of particles. The liquid crystallization ability of the polymers, control of molecular weight distribution, and the polymerization kinetics are identified as three key factors controlling the NP formation. The uniformity of these NPs facilitates their SA formation into colloidal crystals. The particles exhibit optically anisotropic properties depending on orientations and, in particular, show intriguing photoswitchable LC-glass (order-disorder) transition, which can be used for the detection of ultraviolet (UV) light and allows the fabrication of photoreversible colloidal films.

A Conductive and Anti-impact Composite for Flexible Piezoresistive Sensors.

Flexible piezoresistive sensors, which can convert specific mechanical information (such as compression, bending, tensile, and torsion) into a resistance value change signal through the piezoresistive effect, have attracted more and more attention. However, how to achieve the simple, low-cost fabrication of a piezoresistive sensor is still a challenge. Herein, we report a facile strategy that introduces conductive carbon black (CB) and shear thickening gel (SG) composite into a melamine sponge (MS) to generate an MS-SG-CB composite with a unique force-electric coupling effect. A flexible sensor derived from the MS-SG-CB composite can not only accurately identify deformation signals during static stretching and compression while monitoring human movement status in real time but also recognize electrical signals under dynamic impact in a very short time (6 ms). The 3 × 3 flexible array built on this basis can accurately identify the mass and position of heavy objects. Furthermore, based on the flame-retardant properties of MS, the flame-retardant ammonium polyphosphate (APP) is further introduced into MS-SG-CB to obtain MS-SG-CB-APP composite with excellent flame retardancy and stable temperature electrical response behavior, expanding its application in the field of high temperature trigger alarm.

N-acetylcysteine stimulates the proliferation and differentiation in heat-stressed skeletal muscle cells.

N-acetylcysteine (NAC) is known for its beneficial effects on health due to its antioxidant and antiapoptotic properties. This study explored the protective effects of NAC against oxidative stress in heat-stressed (HS) skeletal muscle cells and its role in promoting muscle development. NAC reduced the heat shock response by decreasing the expression of heat shock protein 70 (HSP70) in HS-induced muscle cells during proliferation and differentiation. NAC also mitigated HS-induced oxidative stress via increasing the antioxidant enzyme levels and reducing oxidant enzyme levels. Treatment with NAC at 2 mM increased cell viability from 43.68% ± 5.14%-66.69% ± 14.43% and decreased the apoptosis rate from 7.89% ± 0.53%-5.17% ± 0.11% in skeletal muscle cells. Additionally, NAC promoted the proliferation and differentiation of HS-induced skeletal muscle cells by upregulating the expression of PAX7, MYF5, MRF4 and MYHC. These findings suggest that NAC alleviates HS-induced oxidative damage in skeletal muscle cells and support muscle development.

LncRNA CYTOR knockdown inhibits tumor development via regulating miR-503-5p/PCSK9 in lung adenocarcinoma.

BACKGROUND: The intricate biological mechanism underlying lung adenocarcinoma (LUAD), characterized by a deficiency of distinctive biomarkers, remain elusive. The presence of Long non-coding RNAs (lncRNAs) have been established to play a role in carcinogenesis. Nevertheless, the regulatory effects and mechanisms of lncRNA CYTOR in LUAD have yet to be elucidated. METHODS: In this study, RT-qPCR and Western blot were adopted to examine gene mRNA and protein expression, respectively. Cell proliferation was evaluated by CCK-8 assays. Transwell was performed to assay cell migration and invasion. The function of CYTOR in vivo was investigated through a xenograft animal model. RESULTS: We observed an apparent upregulation of CYTOR in LUAD. Silencing CYTOR significantly reduced proliferation, migration, and invasion capabilities of LUAD cells. Mechanism analysis indicated that CYTOR targeted the miR-503-5p/PCSK9 axis. Additionally, inhibiting of miR-503-5p partially reversed the inhibitory effects of CYTOR silencing on the malignant progression of LUAD cells. Animal experiments revealed that CYTOR/miR-503-5p/PCSK9 curbed tumor formation of nude mice in vivo. CONCLUSION: These findings demonstrated that lncRNA CYTOR acted as an oncogene in LUAD, regulating tumor malignant progression through the miR-503-5p/PCSK9 axis. This study unveiled a new regulation mechanism of LUAD progression, offering potential therapeutic targets for LUAD.

FLASH proton reirradiation, with or without hypofractionation, mitigates chronic toxicity in the normal murine intestine, skin, and bone.

Background and purpose: The normal tissue sparing afforded by FLASH radiotherapy (RT) is being intensely investigated for potential clinical translation. Here, we studied the effects of FLASH proton RT (F-PRT) in the reirradiation setting, with or without hypofractionation. Chronic toxicities in three murine models of normal tissue toxicity including the intestine, skin, and bone were investigated. Materials and methods: In studies of the intestine, single-dose irradiation was performed with 12 Gy of Standard proton RT (S-PRT), followed by a second dose of 12 Gy of F-PRT or S-PRT. Additionally, a hypofractionation scheme was applied in the reirradiation setting (3 x 6.4 Gy of F-PRT or S-PRT, given every 48 hrs). In studies of skin/bone of the murine leg, 15 Gy of S-PRT was followed by hypofractionated reirradiation with F-PRT or S-PRT (3 x 11 Gy). Results: Compared to reirradiation with S-PRT, F-PRT reduced intestinal fibrosis and collagen deposition in the reirradiation setting and significantly increased survival rate, demonstrating its protective effects on intestinal tissues. In previously irradiated leg tissues, reirradiation with hypofractionated F-PRT created transient dermatitis that fully resolved in contrast to reirradiation with hypofractionated S-PRT. Lymphedema was also alleviated after a second course of radiation with F-PRT, along with significant reductions in the accumulation of fibrous connective tissue in the skin compared to mice reirradiated with S-PRT. The delivery of a second course of fractionated S-PRT induced tibial fractures in 83.3% of the mice, whereas only 20% of mice reirradiated with F-PRT presented with fractures. Conclusion: These studies provide the first evidence of the sparing effects of F-PRT, in the setting of hypofractionated reirradiation. The results support FLASH as highly relevant to the reirradiation regimen where it exhibits significant potential to minimize chronic complications for patients undergoing RT.

Beyond transcription, aryl hydrocarbon receptor plays a protective role in periodontitis by interacting with CaMKII.

BACKGROUND: The aryl hydrocarbon receptor (AhR) has been studied as an intracellular pattern recognition receptor that can identify bacterial pigments. To identify a potential therapeutic target for periodontitis, we investigated the expression of AhR in periodontitis and its role in the pathogenesis of periodontitis. METHODS: First, we analyzed AhR expression in a single-cell dataset from human periodontal tissue. Quantitative polymerase chain reaction (qPCR), immunofluorescence, and immunohistochemistry were used to verify the AhR level. Later, we determined the phenotypes of ligature-induced periodontitis in myeloid-specific AhR-deficient mice (Lyz2-Cre+/- AhRfx/fx), after which RNA sequencing (RNA-seq), qPCR, Western blot, immunofluorescence, and immunohistochemistry were used to investigate the impacts of AhR on periodontitis and its mechanism. Finally, we determined the therapeutic effect of AhR agonist 6-Formylindolo[3,2-b]carbazole (FICZ) administration on murine periodontitis and verified the effects of FICZ on macrophage polarization in vitro. RESULTS: AhR expression was enhanced in macrophages from periodontitis patients. Deletion of AhR from macrophages aggravated ligature-induced periodontitis and promoted the inflammatory response. Calcium/calmodulin-stimulated protein kinase II (CaMKII) phosphorylation was accelerated in AhR-deficient macrophages. Inhibiting CaMKII phosphorylation ameliorated periodontitis in Lyz2-Cre+/- AhRfx/fx mice. FICZ treatment blocked alveolar bone loss and relieved periodontal inflammation. FICZ diminished M1 macrophage polarization and promoted M2 macrophage polarization upon M1 macrophage induction. CONCLUSION: AhR played a protective role in the pathogenesis of periodontitis by orchestrating macrophage polarization via interacting with the CaMKII signaling pathway.

N-Acetylcysteine assists muscle development in offspring of mice subjected to maternal heat stress during pregnancy.

BACKGROUND: Heat stress (HS) has been shown to affect reproductive performance and muscle development negatively in animals. N-Acetylcysteine (NAC) plays a pivotal role in enhancing the antioxidant performance in animals as a recognized antioxidant. The present study assesses the potential of NAC to modulate the reproductive performance and antioxidant function in pregnant mice exposed to HS. The role of NAC in muscle development of offspring mice was also explored. RESULTS: The results showed that NAC supplementation from day 12 to day 18 of gestation increased the number of litters and enhanced the antioxidant function in pregnant mice under HS exposure. It improved the weight and body condition significantly in the offspring mice (P < 0.05). The alleviation of HS-induced muscle impairment with NAC was consistent with the alleviation of apoptosis, the enrichment of the proliferation and differentiation in the offspring mice muscle. N-Acetylcysteine also reversed HS-induced reduction in the cross-sectional area of the leg muscle and increased the proportion of myosin heavy chain IIx (MYHCIIx) in the muscle fiber. CONCLUSION: The results of the present study support the use of NAC at a dose of 100 mg kg-1 body weight as supplement for protecting the offspring derived from pregnant mice exposed to HS from muscle impairment by accelerating proliferation and differentiation. © 2024 Society of Chemical Industry.

Exploring physiological stress response evoked by passive translational acceleration in healthy adults: a pilot study utilizing electrodermal activity and heart rate variability measurements.

Passive translational acceleration (PTA) has been demonstrated to induce the stress response and regulation of autonomic balance in healthy individuals. Electrodermal activity (EDA) and heart rate variability (HRV) measurements are reliable indicators of the autonomic nervous system (ANS) and can be used to assess stress levels. The objective of this study was to investigate the potential of combining EDA and HRV measurements in assessing the physiological stress response induced by PTA. Fourteen healthy subjects were randomly assigned to two groups of equal size. The experimental group underwent five trials of elevator rides, while the control group received a sham treatment. EDA and HRV indices were obtained via ultra-short-term analysis and compared between the two groups to track changes in the ANS. In addition, the complexity of the EDA time series was compared between the 4 s before and the 2-6 s after the onset of PTA to assess changes in the subjects' stress levels in the experimental group. The results revealed a significant increase in the skin conductance response (SCR) frequency and a decrease in the root mean square of successive differences (RMSSD) and high frequency (HF) components of HRV. In terms of stress assessment, the results showed an increase in the complexity of the EDA time series 2-6 s after the onset of PTA. These results indicate an elevation in sympathetic tone when healthy subjects were exposed to a translational transport scenario. Furthermore, evidence was provided for the ability of EDA complexity to differentiate stress states in individual trials of translational acceleration.

Proton FLASH Radiotherapy Ameliorates Radiation-induced Salivary Gland Dysfunction and Oral Mucositis and Increases Survival in a Mouse Model of Head and Neck Cancer.

Head and neck cancer radiotherapy often damages salivary glands and oral mucosa, severely negatively impacting patients' quality of life. The ability of FLASH proton radiotherapy (F-PRT) to decrease normal tissue toxicity while maintaining tumor control compared with standard proton radiotherapy (S-PRT) has been previously demonstrated for several tissues. However, its potential in ameliorating radiation-induced salivary gland dysfunction and oral mucositis and controlling orthotopic head and neck tumor growth has not been reported. The head and neck area of C57BL/6 mice was irradiated with a single dose of radiotherapy (ranging from 14-18 Gy) or a fractionated dose of 8 Gy × 3 of F-PRT (128 Gy/second) or S-PRT (0.95 Gy/second). Following irradiation, the mice were studied for radiation-induced xerostomia by measuring their salivary flow. Oral mucositis was analyzed by histopathologic examination. To determine the ability of F-PRT to control orthotopic head and neck tumors, tongue tumors were generated in the mice and then irradiated with either F-PRT or S-PRT. Mice treated with either a single dose or fractionated dose of F-PRT showed significantly improved survival than those irradiated with S-PRT. F-PRT-treated mice showed improvement in their salivary flow. S-PRT-irradiated mice demonstrated increased fibrosis in their tongue epithelium. F-PRT significantly increased the overall survival of the mice with orthotopic tumors compared with the S-PRT-treated mice. The demonstration that F-PRT decreases radiation-induced normal tissue toxicity without compromising tumor control, suggests that this modality could be useful for the clinical management of patients with head and neck cancer.

Tnfaip8 and Tipe2 Gene Deletion Ameliorates Immediate Proteoglycan Loss and Inflammatory Responses in the Injured Mouse Intervertebral Disc.

OBJECTIVE: TNFAIP8 and TIPE2 belong to TNFa-induced protein 8 (TNFAIP8/TIPE) family. They control apoptosis and direct leukocyte migration. Nucleus pulposus (NP) cell loss is a hallmark of intervertebral disc (IVD) degeneration in response to injury, and inflammation may cause pain. Here, we examined the effects of TNFAIP8/TIPE2 deficiency on the IVDs in mice with these genes deleted. DESIGN: Tail IVDs in Tnfaip8 or Tipe2 single and double knockout mice (Tnfaip8-/-, Tipe2-/-, and Tnfaip8/Tipe2 dko), and wild type (WT) controls were injured. The spine motion segments were stained with Safranin O to reveal proteoglycans. Macrophages were identified by immunostaining, and selected inflammatory marker and collagen gene expression was examined by Real Time PCR. RESULTS: The injured tail IVDs of Tnfaip-/-, Tipe2-/-, and Tnfaip8/Tipe2 dko mice all displayed higher levels of proteoglycans than WT controls. Fewer macrophages were found in the injured IVDs of Tipe2-/- and Tnfaip8/Tipe2 dko mice than WT. Il6, Adam8 and Col1 gene expression was downregulated in the injured IVDs of Tnfip8/Tipe2 dko mice. CONCLUSIONS: TNFAIP8 and TIPE2 loss of function ameliorated proteoglycan loss and inflammation in the injured IVDs. They may serve as molecular targets to preserve disc structure and reduce inflammation.

Synovium and infrapatellar fat pad share common mesenchymal progenitors and undergo coordinated changes in osteoarthritis.

Osteoarthritis (OA) affects multiple tissues in the knee joint, including the synovium and intra-articular adipose tissue (IAAT) that are attached to each other. However, whether these two tissues share the same progenitor cells and hence function as a single unit in joint homeostasis and diseases is largely unknown. Single-cell transcriptomic profiling of synovium and infrapatellar fat pad (IFP), the largest IAAT, from control and OA mice revealed five mesenchymal clusters and predicted mesenchymal progenitor cells (MPCs) as the common progenitors for other cells: synovial lining fibroblasts (SLFs), myofibroblasts (MFs), and preadipocytes 1 and 2. Histologic examination of joints in reporter mice having Dpp4-CreER and Prg4-CreER that label MPCs and SLFs, respectively, demonstrated that Dpp4+ MPCs reside in the synovial sublining layer and give rise to Prg4+ SLFs and Perilipin+ adipocytes during growth and OA progression. After OA injury, both MPCs and SLFs gave rise to MFs, which remained in the thickened synovium at later stages of OA. In culture, Dpp4+ MPCs possessed mesenchymal progenitor properties, such as proliferation and multilineage differentiation. In contrast, Prg4+ SLFs did not contribute to adipocytes in IFP and Prg4+ cells barely grew in vitro. Taken together, we demonstrate that the synovium and joint fat pad are one integrated functional tissue sharing common mesenchymal progenitors and undergoing coordinated changes during OA progression.

Both synovium and intra-articular adipose tissue (IAAT) in knee joint play a critical role in joint health and osteoarthritis (OA) progression. Recent single-cell RNA-sequencing studies have been performed on the mouse and human synovium. However, IAATs residing in close proximity to the synovium have not been studied yet. Our study reveals mesenchymal cell heterogeneity of synovium/infrapatellar fat pad (Syn/IFP) tissue and their OA responses. We identify Dpp4+ multipotent progenitors as a source that give rise to Prg4+ lining layer fibroblasts in the synovium, adipocytes in the IFP, and myofibroblasts in the OA Syn/IFP tissue. Our work demonstrates that Syn/IFP is a functionally connected tissue that shares common mesenchymal progenitors and undergoes coordinated OA changes. This novel insight advances our knowledge of previously understudied joint tissues and provides new directions for drug discovery to treat joint disorders.

How do national marine parks contribute to tourism eco-efficiency in coastal cities? The case of China.

This research investigates how establishing national marine parks in China enhances marine tourism ecology. Analyzing data from 52 coastal cities between 2006 and 2019, it uses a multi-period difference-in-differences method to evaluate the parks' impact on tourism eco-efficiency. The results show that national marine parks significantly improve coastal cities' tourism eco-efficiency, especially in the Bohai Rim and seaside cities. The study attributes this improvement to the reduction of fixed asset investments, which controls the scale of tourism development. These findings provide vital insights for countries seeking to revitalize their marine tourism sectors through similar ecological restoration strategies.

Efficacy and safety of Ruxolitinib, Crisaborole, and Tapinarof for mild-to-moderate atopic dermatitis: a Bayesian network analysis of RCTs.

Given the lack of head-to-head studies of novel non-steroidal molecule topical therapies in mild-to-moderate atopic dermatitis (AD), network meta-analyses (NMAs) can provide comparative efficacy and safety data for clinical decision-making. In this NMA, we performed a literature search until 01 March 2023 for eligible studies written in English using databases, including PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov. Only double-blind randomized clinical trials (RCTs) with topical Ruxolitinib, Crisaborole, or Tapinarof versus vehicle for patients with mild-to-moderate AD were included. Baseline and follow-up data were extracted. Efficacy was evaluated using Investigator's Global Assessment (IGA) achieving "clear" or "almost clear," with 2 points or more improvement from baseline at the end of treatment, referred to as "IGA success." For binary outcomes, we analyzed in random-effects Bayesian NMA consistency models to compare the efficacy of these 3 topical therapies by odds ratio (OR) with 95% credibility interval (CrI). Overall, 10 phase 2 or phase 3 RCTs were identified, which included 4010 patients with mild to moderate AD. Compared with the topical vehicle control, all these 3 treatments had higher response rate of "IGA success" at the end of trial (Ruxolitinib 1.5% b.i.d: OR, 11.94; 95%CrI, 6.28-23.15; Crisaborole 2% b.i.d: OR, 2.08; 95%CrI, 1.46-3.52; Tapinarof 1% b.i.d: OR, 2.64; 95%CrI, 0.75-9.70). Notably, Ruxolitinib 1.5% b.i.d. had the highest probability of achieving "IGA success" in ranking analysis (Rank 1, SUCRA = 0.75) and lower risk of AE (Rank 8, SUCRA = 0.22). Besides, there was no difference in treatment-related adverse events between 3 therapies. Heterogeneity was not significant across studies.

Identification of Shared Biomarkers and Immune Infiltration Signatures between Vitiligo and Hashimoto's Thyroiditis.

Background: Vitiligo and Hashimoto's thyroiditis (HT) are concomitant autoimmune diseases characterized by the destruction of melanocytes or thyrocytes. We aimed to explore the immunological mechanism of this comorbidity and screen their potential biomarkers. Methods: We downloaded the microarray datasets from the GEO database. Differentially expressed genes (DEGs) and immune-related genes (IRGs) were selected. The immune-related differentially expressed genes (IRDEGs) were obtained by taking the intersection. Candidate biomarkers were elected by Cytoscape software. CIBERSORT was used to depict immune cell infiltration prospects. Correlation analysis was conducted between infiltrating cells and several indicators. The results were validated by real-time quantitative PCR (RT-qPCR). Results: Three datasets and 60 IRDEGs were obtained in total. Pathway enrichment analysis showed that the T cell receptor signaling pathway, IL-17 signaling pathway, receptor-ligand activity, and signaling receptor activator activity were significantly enriched. We screened out four hub genes, including IFNG, STAT1, IL1B, and CXCL10. The ROC curve indicated the highest diagnostic value of CXCL10 in both vitiligo and HT. Immuno-infiltration analysis revealed significant changes in T cell subsets and macrophage subtypes, which were correlated with four hub genes, melanocyte markers, and thyroid-specific antigens. qPCR validated the hub genes in peripheral blood mononuclear cells from patients with comorbidity. Conclusion: IFNG, STAT1, IL1B, and CXCL10, were the key IRDEGs to vitiligo and HT. These genes may participate in the comorbidity by remodeling the immune cell infiltration pattern, and cross-expressed antigens may mediate the common damage of melanocytes and thyroid tissues.

The causal effects of circulating cytokines on sepsis: a Mendelian randomization study.

Background: In observational studies, sepsis and circulating levels of cytokines have been associated with unclear causality. This study used Mendelian randomization (MR) to identify the causal direction between circulating cytokines and sepsis in a two-sample study. Methods: An MR analysis was performed to estimate the causal effect of 41 cytokines on sepsis risk. The inverse-variance weighted random-effects method, the weighted median-based method, and MR-Egger were used to analyze the data. Heterogeneity and pleiotropy were assessed using MR-Egger regression and Cochran's Q statistic. Results: Genetically predicted beta-nerve growth factor (OR = 1.12, 95% CI [1.037-1.211], P = 0.004) increased the risk of sepsis, while RANTES (OR = 0.92, 95% CI [0.849-0.997], P = 0.041) and fibroblast growth factor (OR = 0.869, 95% CI [0.766-0.986], P = 0.029) reduced the risk of sepsis. These findings were robust in extensive sensitivity analyses. There was no clear association between the other cytokines and sepsis risk. Conclusion: The findings of this study demonstrate that beta-nerve growth factor, RANTES, and fibroblast growth factor contribute to sepsis risk. Investigations into potential mechanisms are warranted.

The Impact of Preoperative Adaptive Training on Postoperative Outcomes in Lumbar Spine Fusion Surgery for Lumbar Disc Herniation: A Retrospective Analysis.

Purpose: Lumbar disc herniation, often treated with surgical decompression when conservative measures fail, presents challenges due to prolonged prone positioning in surgeries. This retrospective study evaluates the benefits of preoperative adaptive training to mitigate post-surgical physiological changes. Patients and Methods: A review of medical records from June 2021 to March 2023 identified 170 patients unresponsive to conservative treatments. Grouped into adaptive training and control groups based on historical data, the former had undergone exercises to prepare for surgery and postoperative changes. Vital signs and VAS scores were extracted from patient records to assess training impact. Results: The adaptive training group demonstrated stabilized vital signs intraoperatively, with a notable improvement in surgical exposure compared to the control group. However, there were no significant differences in operative time or blood loss between the groups. Additionally, postoperative VAS scores showed no significant improvement in the adaptive training group at follow-up intervals of 14 days, 1 month, and 3 months post-operation, compared to the control group. Conclusion: Our study reveals that preoperative adaptive training stabilizes intraoperative blood pressure fluctuations in lumbar disc herniation surgeries. However, this stabilization does not significantly impact long-term postoperative pain management. This highlights the need for further research to explore comprehensive strategies that effectively combine preoperative training with postoperative care.

Efficacy and safety of Shenqi Fuzheng injection combined with chemotherapy for cancer: An overview of systematic reviews.

BACKGROUND: In China, Shenqi Fuzheng injection (SFI) has been used as an adjuvant therapy to treat all kinds of cancer for many years. A large number of systematic reviews or meta-analyses (SRs/MAs) were published to assess its efficacy and safety in the past few years. However, the quality of SRs/MAs was unclear and did not generate high-quality clinical evidence. OBJECTIVE: We conducted an overview to integrate relevant SRs/MAs published in the past with the aim of providing new clinical evidence for SFI in combination with chemotherapy in the treatment of cancer. OBJECTIVE: We conducted an overview to integrate relevant SRs/MAs published in the past with the aim of providing new clinical evidence for SFI in combination with chemotherapy in the treatment of cancer. METHODS: A comprehensive search of PubMed, Web of Science, Embase, the Cochrane Library, CNKI, VIP, WanFang, and CBM was performed from the database inception to September 30, 2023. SRs/MAs of randomized controlled trials (RCTs) on SFI combined with chemotherapy for cancer were included. Four reviewers screened the literature and extracted relevant information. Five reviewers assessed the quality of reporting, methodological quality, risk of bias, and quality of evidence for SRs/MAs. We used corrected covered area (CCA) to assess the degree of overlap among the RCTs included in SRs/MAs. We performed a descriptive analysis for the results of the included SRs/MAs. RESULTS: A total of 32 SRs/MAs of SFI combined with chemotherapy for cancer were included. We assessed the reporting quality of SRs/MAs using the PRISMA 2020 statement. 1 SR/MA had relatively complete reports, 20 SRs/MAs had some deficiencies in reporting, and 11 SRs/MAs had serious deficiencies in reporting. We assessed the methodological quality of SRs/MAs using the AMSTAR 2 tool. The methodological quality of all SRs/MAs was very low. We assessed the risk of bias for SRs/MAs using the ROBIS tool. The risk of bias was low for 19 SRs/MAs and unclear for 13 SRs/MAs. We assessed the quality of evidence for SRs/MAs using the GRADE evidence quality evaluation system. 50 items were moderate quality, 46 items were low quality, 27 items were very low quality, and 85 items were unclear. SFI combined with chemotherapy played a role in increasing efficacy and decreasing toxicities in all kinds of cancer, including clinical efficacy (except liver cancer), quality of life, immune function (except CD8+), leukopenia, thrombocytopenia, hemoglobinopenia, nausea and vomiting, liver damage, kidney damage, neurotoxicity, alopecia, and diarrhea. CONCLUSION: The overview showed that SFI combined with chemotherapy may improve clinical efficacy (except for liver cancer), quality of life, and immune (except for CD8+) function in all types of cancer, as well as adverse events (AEs) such as leukopenia, thrombocytopenia, etc. Since most of the clinical evidence was low, higher quality clinical trials will be expected to improve the reliability of the above conclusions in the future.