In situ biomineralization reinforcing anisotropic nanocellulose scaffolds for guiding the differentiation of bone marrow-derived mesenchymal stem cells.

Nanocellulose (NC) is a promising biopolymer for various biomedical applications owing to its biocompatibility and low toxicity. However, it faces challenges in tissue engineering (TE) applications due to the inconsistency of the microenvironment within the NC-based scaffolds with target tissues, including anisotropy microstructure and biomechanics. To address this challenge, a facile swelling-induced nanofiber alignment and a novel in situ biomineralization reinforcement strategies were developed for the preparation of NC-based scaffolds with tunable anisotropic structure and mechanical strength for guiding the differentiation of bone marrow-derived mesenchymal stem cells for potential TE application. The bacterial cellulose (BC) and cellulose nanofibrils (CNFs) based scaffolds with tunable swelling anisotropic index in the range of 10-100 could be prepared by controlling the swelling medium. The in situ biomineralization efficiently reinforced the scaffolds with 2-4 times and 10-20 times modulus increasement for BC and CNFs, respectively. The scaffolds with higher mechanical strength were superior in supporting cell growth and proliferation, suggesting the potential application in TE application. This work demonstrated the feasibility of the proposed strategy in the preparation of scaffolds with mechanical anisotropy to induce cells-directed differentiation for TE applications.

Supplementation with Combined Additive Improved the Production of Dairy Cows and Their Offspring with Maintenance of Antioxidative Stability.

Oxidative stress damage in periparturient cows decreases both production and their health; supplementation with complex additives during the periparturient period has been used as an important strategy to enhance the antioxidant status and production of dairy cows. The periparturient cows not only risk a negative energy balance due to reduced dry matter intake but also represent a sensitive period for oxidative stress. Therefore, we have developed an immunomodulatory and nutritional regulation combined additive (INC) that hopefully can improve the immune status and production of cows during the periparturient period and their offspring health and growth by improving their antioxidant stress status. The INC comprised a diverse array of additives, including water-soluble and fat-soluble vitamins, Selenomethionine, and active dry Saccharomyces cerevisiae. Forty-five multiparous Holstein cows were randomly assigned to three treatments: CON (no INC supplementation, n = 15), INC30 (30 g/d INC supplementation, n = 15), and INC60 (60 g/d INC supplementation, n = 15) based on last lactation milk yield, body condition score, and parity. Newborn calves were administered 4 L of maternal colostrum originating from the corresponding treatment and categorized based on the treatment received by their respective dams. The INC not only served to maintain the antioxidative stress system of dairy cows during the periparturient period but also showed a tendency to improve the immune response (lower tumor necrosis factor and interleukin-6) during the perinatal period. A linear decrease in concentrations of alkaline phosphatase postpartum and ß-hydroxybutyrate was observed with INC supplementation. Milk fat yield, milk protein yield, and energy-corrected milk yield were also increased linearly with increasing additive supplementation. Calves in the INC30 group exhibited greater wither height and chest girth but no significant effect on average daily gain or body weight. The diarrhea frequency was linearly decreased with the incremental level of INC. Results indicate that supplementation with INC in peripartum dairy cows could be a major strategy to improve immune response, decrease inflammation, maintain antioxidant stress status in transition dairy cows, and have merit in their calves. In conclusion, this study underlines the benefits of INC supplementation during the transition period, as it improved anti-inflammatory capacity, could positively impact antioxidative stress capacity, and eventually enhanced the production performance of dairy cows and the health and growth of calves.

NRDE2 deficiency impairs homologous recombination repair and sensitizes hepatocellular carcinoma to PARP inhibitors.

To identify novel susceptibility genes for hepatocellular carcinoma (HCC), we performed a rare-variant association study in Chinese populations consisting of 2,750 cases and 4,153 controls. We identified four HCC-associated genes, including NRDE2, RANBP17, RTEL1, and STEAP3. Using NRDE2 (index rs199890497 [p.N377I], p = 1.19 × 10-9) as an exemplary candidate, we demonstrated that it promotes homologous recombination (HR) repair and suppresses HCC. Mechanistically, NRDE2 binds to the subunits of casein kinase 2 (CK2) and facilitates the assembly and activity of the CK2 holoenzyme. This NRDE2-mediated enhancement of CK2 activity increases the phosphorylation of MDC1 and then facilitates the HR repair. These functions are eliminated almost completely by the NRDE2-p.N377I variant, which sensitizes the HCC cells to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with chemotherapy. Collectively, our findings highlight the relevance of the rare variants to genetic susceptibility to HCC, which would be helpful for the precise treatment of this malignancy.

A structure-functionality insight into the bioactivity of microbial polysaccharides toward biomedical applications: A review.

Microbial polysaccharides (MPs) are biopolymers secreted by microorganisms such as bacteria and fungi during their metabolic processes. Compared to polysaccharides derived from plants and animals, MPs have advantages such as wide sources, high production efficiency, and less susceptibility to natural environmental influences. The most attractive feature of MPs lies in their diverse biological activities, such as antioxidative, anti-tumor, antibacterial, and immunomodulatory activities, which have demonstrated immense potential for applications in functional foods, cosmetics, and biomedicine. These bioactivities are precisely regulated by their sophisticated molecular structure. However, the mechanisms underlying this precise regulation are not yet fully understood and continue to evolve. This article presents a comprehensive review of the most representative species of MPs, including their fermentation and purification processes and their biomedical applications in recent years. In particular, this work presents an in-depth analysis into the structure-activity relationships of MPs across multiple molecular levels. Additionally, this review discusses the challenges and prospects of investigating the structure-activity relationships, providing valuable insights into the broad and high-value utilization of MPs.

Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2.

Cancer-associated Fibroblasts (CAFs) exert a tumor-promoting effect in various cancers, including breast cancer. CAFs secrete exosomes containing miRNA and proteins, influencing the tumor microenvironment. In this study, we identified CAF-derived exosomes that transport functional miR-92a from CAFs to tumor cells, thereby intensifying the aggressiveness of breast cancer. CAFs downregulate the expression of G3BP2 in breast cancer cells, and a significant elevation in miR-92a levels in CAF-derived exosomes was observed. Both in vitro and in vivo experiments demonstrate that miR-92a enhances breast cancer cell migration and invasion by directly targeting G3BP2, functioning as a tumor-promoting miRNA. We validated that the RNA-binding proteins SNRPA facilitate the transfer of CAF-derived exosomal miR-92a to breast cancer cells. The reduction of G3BP2 protein by CAF-derived exosomes releases TWIST1 into the nucleus, promoting epithelial-mesenchymal transition (EMT) and further exacerbating breast cancer progression. Moreover, CAF-derived exosomal miR-92a induces tumor invasion and metastasis in mice. Overall, our study reveals that CAF-derived exosomal miR-92a serves as a promoter in the migration and invasion of breast cancer cells by reducing G3BP2 and may represent a potential novel tumor marker for breast cancer.

Compatibilization of Immiscible Polypropylene/Poly(methyl methacrylate) Blends by Silica Particles with Janus and Random Component-Selective Grafts.

Introducing component-selective polymer chains onto the surface of a particle is an effective approach to improve the compatibilization efficiency of a particle-based compatibilizer. In this study, two particles with different kinds of component-selective polymer chains that have the same length and similar density but different graft locations were synthesized and their compatibilization effects were comparatively investigated. It was found that compared with the particle with homogeneous PMMA and PP grafts (R-P), the particle with a hemisphere of poly(methyl methacrylate) (PMMA) grafts and other hemisphere of polypropylene (PP) chains (J-P) showed a better compatibilization effect under equal loadings, although both particles exhibited high efficiency. The better compatibilization effect of particles with Janus grafts may be attributed to the stronger entanglements between grafted polymer chains and selective individual components. This work suggests that optimizing the graft location of a particle is an effective strategy for improving its compatibilization efficiency and helpful for the design of advanced particle compatibilizers.

Transcranial Direct Current Stimulation for Anxiety During Laparoscopic Colorectal Cancer Surgery: A Randomized Clinical Trial.

Importance: Perioperative anxiety is prevalent among patients undergoing surgical treatment of cancer and often influences their prognosis. Transcranial direct current stimulation (tDCS) has shown potential in the treatment of various anxiety-related disorders, but data on the impact of tDCS on perioperative anxiety are limited. Objective: To evaluate the effect of tDCS in reducing perioperative anxiety among patients undergoing laparoscopic colorectal cancer (CRC) resection. Design, Setting, And Participants: This randomized clinical trial was conducted from March to August 2023 at the Affiliated Hospital of Xuzhou Medical University. Patients aged 18 years or older undergoing elective laparoscopic radical resection for CRC were randomly assigned to either the active tDCS group or the sham tDCS group. Intention-to-treat data analysis was performed in September 2023. Interventions: Patients were randomly assigned to receive 2 sessions of either active tDCS or sham tDCS over the left dorsolateral prefrontal cortex on the afternoon of the day before the operation and in the morning of the day of operation. Main Outcomes and Measures: The main outcome was the incidence of perioperative anxiety from the day of the operation up to 3 days after the procedure, as measured using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale (range: 0-21, with higher scores indicating more anxiety). Secondary outcomes included postoperative delirium (assessed by the Confusion Assessment Method or Confusion Assessment Method intensive care unit scale); pain (assessed by the 10-point Numeric Rating Scale [NRS], with scores ranging from 0 [no pain] to 10 [worst pain]); frailty (assessed by the Fatigue, Resistance, Ambulation, Illness and Loss of Weight [FRAIL] Index, with scores ranging from 0 [most robust] to 5 [most frail]; and sleep quality (assessed by the Pittsburgh Sleep Quality Index [PSQI], with scores ranging from 0 to 21 and higher scores indicating worse sleep quality) after the 2 sessions of the tDCS intervention. Results: A total of 196 patients (mean [SD] age, 63.5 [11.0] years; 124 [63.3%] men) were recruited and randomly assigned to the active tDCS group (98 patients) or the sham tDCS group (98 patients). After the second tDCS intervention on the day of the operation, the incidence of perioperative anxiety was 38.8% in the active tDCS group and 70.4% in the sham tDCS group (relative risk, 0.55 [95% CI, 0.42-0.73]; P < .001). Patients in the active tDCS group vs the sham tDCS group were less likely to have postoperative delirium (8.2% vs 25.5%) and, at 3 days after the operation, had lower median (IQR) pain scores (NRS, 1.0 [1.0-1.0] vs 2.0 [2.0-2.0]), better median (IQR) sleep quality scores (PSQI, 10.5 [10.0-11.0] vs 12.0 [11.0-13.0]), and lower median (IQR) FRAIL Index (2.0 [1.0-2.0] vs 2.0 [2.0-3.0]). Conclusions and Relevance: Findings of this randomized clinical trial indicate that administration of 2 preoperative sessions of tDCS was associated with a decreased incidence of perioperative anxiety in patients undergoing elective CRC resection. Active tDCS was also associated with better anxiety scores, pain levels, and sleep quality as well as reduced postoperative delirium and frailty. The findings suggest that tDCS may be a novel strategy for improving perioperative anxiety in patients undergoing CRC resection. Trial Registration: Chinese Clinical Trial Register Identifier: ChiCTR2300068859.

Comparative efficacy and safety of Chinese medicine injections as an adjunctive therapy for cervical cancer in Chinese patients: a network meta-analysis.

CONTEXT: Chinese medicine injections (CMIs) are widely used as adjuvant therapy for cervical cancer in China. However, the effectiveness of different types of CMIs remains uncertain. OBJECTIVE: To assess the effectiveness and safety of CMIs when used in conjunction with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT), particularly in combination with cisplatin (DDP), docetaxel plus cisplatin (DP), and paclitaxel plus cisplatin (TP). MATERIALS AND METHODS: Randomized controlled trials (RCTs) were searched in databases including CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library, Embase, and Web of Science from inception to September 2023. We calculated the risk ratio with a 95% confidence interval and the surface under the cumulative ranking area curve (SUCRA) for the clinical efficacy rate (CER), the efficacy rate by Karnofsky Performance Status (KPS), and the rates of leukopenia reduction (LRR) and gastrointestinal reactions (GRR). RESULTS: Forty-seven RCTs were included, including nine CMI types: Aidi, Fufangkushen, Huangqi, Kangai (KA), Kanglaite (KLT), Renshenduotang, Shenqifuzheng (SQFZ), Shenmai (SM), and Yadanzi. KLT and KA were likely optimal choices with radiotherapy for CER and KPS, respectively. KA and KLT were optimal choices with RT + DDP for CER and GRR, respectively. KLT was the likely optimal choice with RT + DP for CER and KA for both KPS and GRR. SM and SQFZ were the likely optimal choices with RT + TP for CER and LRR, respectively. CONCLUSIONS: The optimal recommendation depends on whether CMIs are used with radiotherapy or concurrent chemoradiotherapy. More high-quality RCTs are needed to confirm further and update the existing evidence.

Return to flight duty (RTFD) after posterior lumbar spine surgery for symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) in Chinese military pilots.

BACKGROUND: Symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) present significant challenges for military pilots, which may result in grounding if not effectively managed. Surgical treatment for LDH and LIS may offer a pathway to return to flight duty (RTFD), but recent data on this crucial topic is lacking. This study seeks to address this gap by investigating the RTFD outcomes among Chinese military pilots who have undergone lumbar spine surgery for symptomatic LDH and LIS. METHODS: A retrospective review was conducted on active-duty military pilots who underwent isolated decompressive or fusion procedures at an authorized military medical center from March 1, 2007, to March 1, 2023. The analysis utilized descriptive statistics to examine demographic, occupational, surgical, and outcome data, with a particular focus on preoperative flight status, recommended clearance by spine surgeons, and actual RTFD outcomes and time. RESULTS: Among the identified cases of active-duty military pilots with LDH or LIS treated by lumbar surgery (n = 24), 70.8% (17 of 24) consistently maintained RTFD status without encountering surgical complications or medical issues during the follow-up period. Of the seven pilots who did not RTFD, one retired within a year of surgery, two had anterior cruciate ligament injuries, three had residual radicular symptoms, and one had chronic low back pain. Excluding pilots who retired and did not RTFD for reasons unrelated to their lumbar conditions, the RTFD rate stood at 81.0% (17 of 21). The median time for recommended clearance by spine surgeons was 143.0 days (inter-quartile range, 116.5-196.0), while the median duration for actual RTFD attainment was 221.0 days (inter-quartile range, 182.0-300.0). The median follow-up post-lumbar surgery was 1.7 years (inter-quartile range, 0.4-2.9). CONCLUSION: Most military pilots diagnosed with symptomatic LDH and LIS can continue their careers and regain active-duty flight status following lumbar spine surgery, as reflected by the high RTFD rate. Lumbar spine surgery can successfully alleviate the physical constraints associated with spinal conditions, facilitating the return of military pilots to their demanding profession.

A Silicon-Rhodamine-Based Heavy-Atom-Free Photosensitizer for Mitochondria-targeted Photodynamic Therapy.

Silicon-xanthene derivatives (SiXs) have gained popularity in the field of bioimaging due to their advantageous far-red to near-infrared (NIR) absorption and emission wavelengths, notable brightness (ε × Φ), inherent mitochondrial targeting properties and high photo-stability, making them an excellent candidate for photodynamic therapy (PDT). Nevertheless, the utilization of SiXs as photosensitizers (PSs) for PDT in cancer treatment remains largely unexplored, primarily due to their limited capacity to generate cytotoxic reactive oxygen species (ROS). However, the potential of SiXs in PDT warrants further investigation. In this study, utilizing the spin-orbit charge transfer-induced intersystem crossing (SOCT-ISC) mechanism, we reported one novel heavy-atom-free, mitochondria-targeted, silicon-rhodamine-based photosensitizer (SiR-PXZ), which demonstrated excellent biocompatibility, minimal dark toxicity, favorable water-solubility and stability, and considerable singlet oxygen quantum yield under 660 nm light irradiation (ΦΔ = 0.16 in air-saturated PBS). Moreover, SiR-PXZ could be rapidly taken up by the mitochondria and efficiently induced apoptosis of cancer cells with an IC50 value of 1.2 µM. The in vivo studies showed that SiR-PXZ exhibited excellent anti-tumor effects, making it potentially valuable for clinical application. This study offers a source of ideas for the construction of SiXs-based photosensitizers for photodynamic cancer treatment in the future.

Lactobacillus plantarum Zhang-LL Inhibits Colitis-Related Tumorigenesis by Regulating Arachidonic Acid Metabolism and CD22-Mediated B-Cell Receptor Regulation.

Colorectal cancer (CRC) is a significant health concern and is the third most commonly diagnosed and second deadliest cancer worldwide. CRC has been steadily increasing in developing countries owing to factors such as aging and epidemics. Despite extensive research, the exact pathogenesis of CRC remains unclear, and its causes are complex and variable. Numerous in vitro, animal, and clinical trials have demonstrated the efficacy of probiotics such as Lactobacillus plantarum in reversing the adverse outcomes of CRC. These findings suggest that probiotics play vital roles in the prevention, adjuvant treatment, and prognosis of CRC. In this study, we constructed a mouse model of CRC using an intraperitoneal injection of azomethane combined with dextran sodium sulfate, while administering 5-fluorouracil as well as high- and low-doses of L. plantarum Zhang-LL live or heat-killed strains. Weight changes and disease activity indices were recorded during feeding, and the number of polyps and colon length were measured after euthanasia. HE staining was used to observe the histopathological changes in the colons of mice, and ELISA was used to detect the expression levels of IL-1ß, TNF-α, and IFN-γ in serum. To investigate the specific mechanisms involved in alleviating CRC progression, gut microbial alterations were investigated using 16S rRNA amplicon sequencing and non-targeted metabolomics, and changes in genes related to CRC were assessed using eukaryotic transcriptomics. The results showed that both viable and heat-killed strains of L. plantarum Zhang-LL in high doses significantly inhibited tumorigenesis, colon shortening, adverse inflammatory reactions, intestinal tissue damage, and pro-inflammatory factor expression upregulation. Specifically, in the gut microbiota, the abundance of the dominant flora Acutalibacter muris and Lactobacillus johnsonii was regulated, PGE2 expression was significantly reduced, the arachidonic acid metabolism pathway was inhibited, and CD22-mediated B-cell receptor regulation-related gene expression was upregulated. This study showed that L. plantarum Zhang-LL live or heat-inactivated strains alleviated CRC progression by reducing the abundance of potentially pathogenic bacteria, increasing the abundance of beneficial commensal bacteria, mediating the arachidonic acid metabolism pathway, and improving host immunogenicity.

Return to active duty after anterior cruciate ligament reconstruction (ACLR) in Chinese male military aircrews.

Background: Surgically treated anterior cruciate ligament (ACL) injuries may be a waivable condition and allow return to full flight status, but waivers are based on expert opinion rather than recent published data. The purpose of this study was to evaluate return to flight after anterior cruciate ligament reconstruction (ACLR) in male military aircrews with ACL injuries and to identify factors that affect flight clearance. Method: A single-center retrospective review was conducted by the authors for all active-duty aircrew who underwent ACLR at an authorized military medical center from January 2010 to December 2019. Demographic characteristics, occupational information, surgical data, and flight readiness evaluation outcomes were collected. Based on the final medical evaluation, subjects were divided into a qualified group (N = 64) and a disqualified group (N = 9), and the difference in data collected between the two groups was then analyzed to identify factors affecting flight clearance. Results: A total of 73 patients underwent successful ACLR with a mean age of 31.6 ± 5.6 years. Non-contact injury was the main type of ACL injury, accounting for 84.9% of the total injuries. 55 cases (75.3%) occurred during daily sports activities and 18 (24.7%) during military training. 64 of the 73 crewmembers (87.7%) were able to return to flight at their last follow-up evaluation. The preoperative interval time (PIT) was significantly less in the qualified group than in the disqualified group (P = 0.002). Patients who underwent ACLR within three months were more likely to return to flying than those who underwent the procedure three months later (97.4% vs. 76.5%, P = 0.010). The incidence of failure to return to flight duty was significantly higher in aircrews with ACL injuries combined with meniscal injuries than in aircrews with isolated ACL injuries (21.4% vs. 0.0%, P = 0.017). Conclusion: ACLR appears to be safe for military aircrew suffering ACL injuries with or without meniscal injury, and return to flight status is the most likely outcome for the majority of postoperative pilots. Prolonged PIT, PIT > 3 months, and ACL injury combined with meniscus injury had a negative impact on postoperative flight readiness.

[Posterior cervical pedicle screw rod short-segment internal fixation for the treatment of atlantoaxial fracture and dislocation].

OBJECTIVE: To investigate the clinical efficacy of posterior cervical pedicle screw short-segment internal fixation for the treatment of atlantoaxial fracture and dislocation. METHODS: The clinical data of 60 patients with atlantoaxial vertebral fracture and dislocation underwent surgery between January 2015 and January 2018 were retrospectively analyzed. The patients were divided into study group and control group according to different surgical methods. There were 30 patients in study group, including 13 males and 17 females, with an average age of (39.32±2.85) years old, were underwent short-segment internal fixation with posterior cervical pedicle screws. There were 30 patients in control group, including 12 males and 18 females, with an average age of (39.57±2.90) years old, were underwent posterior lamina clip internal fixation of the atlas. The operation time, intraoperative blood loss, postoperative ambulation time, hospitalization time and complications between two groups were recorded and compared. The pain visual analogue scale(VAS), Japanese Orthopedic Association(JOA) score of neurological function, and fusion status were evaluated between two groups. RESULTS: All patients were followed up for at least 12 months. The study group was better than control group in operation time, intraoperative blood loss, postoperative off-bed activity time, and hospital stay (P=0.000). One case of respiratory tract injury occurred in study group. In control group, 2 cases occurred incision infection, 3 cases occurred respiratory tract injury, and 3 cases occurred adjacent segmental joint degeneration. The incidence of complications in study group was lower than that in control group (χ2=4.705, P=0.030). At 1, 3, 7 days after operation, VAS of study group was lower than that of control group(P=0.000). At 1, 3 months after operation, JOA score of study group was higher than that of control group(P=0.000). At 12 months after operation, all the patients in the study group achieved bony fusion. In control group, there were 3 cases of poor bony fusion and 3 cases of internal fixation fracture, the incidence rate was 20.00%(6/30). The difference between two groups was statistically significant (χ2=4.629, P=0.031). CONCLUSION: Posterior cervical short-segment pedicle screw fixation for atlantoaxial fracture and dislocation has the advantages of less trauma, shorter operation time, fewer complications, and less pain, and can promote the recovery of nerve function as soon as possible.

miR-424-3p promotes metastasis of hepatocellular carcinoma via targeting the SRF-STAT1/2 axis.

Although emerging evidence has established the roles of miRNAs in hepatocellular carcinoma (HCC), the global functional implication of miRNAs in this malignancy remains largely uncharacterized. Here, we aim to systematically identify novel miRNAs involved in HCC and clarify the function and mechanism of specific novel candidate miRNA(s) in this malignancy. Through an integrative omics approach, we identified ten HCC-associated functional modules and a collection of candidate miRNAs. Among them, we demonstrated that miR-424-3p, exhibiting strong associations with extracellular matrix (ECM), promotes HCC cells migration and invasion in vitro and facilitates HCC metastasis in vivo. We further demonstrated that SRF is a direct functional target of miR-424-3p, and is required for the oncogenic activity of miR-424-3p. Finally, we found that miR-424-3p reduces the interferon pathway by attenuating the transactivation of SRF on STAT1/2 and IRF9 genes, which in turn enhances the matrix metalloproteinases (MMPs)-mediated ECM remodeling. This study provides comprehensive functional relevance of miRNAs in HCC by an integrative omics analysis, and further clarifies that miR-424-3p in ECM functional module plays an oncogenic role via reducing the SRF-STAT1/2 axis in this malignancy.

Liver cancer cell-secreted exosomes promote bone metastasis of liver cancer by facilitating osteoclast differentiation through the miR-574-5p/BMP2 axis.

Bone metastasis of liver cancer leads to a worse prognosis with no appropriate treatment clinically. Exosomes are associated with tumor bone metastasis. This study aimed to investigate the effects of liver cancer cell-derived exosomes on bone metastasis. Exosomes were isolated from Hep3B cells, and the effects of osteoclast differentiation were assessed using TRAP assay. The expression of OPG and RANKL was assessed using qRT-PCR. The interaction of miR-574-5p and BMP2 was analyzed using luciferase reporter analysis, RNA pull-down, and qRT-PCR. We found that Hep3B cells promoted osteoclast differentiation of RANKL-induced Raw264.7 cells by secreting exosomes, with decreased OPG and increased RANKL expression. The exosomes were isolated from Hep3B cells, which promoted osteoclast differentiation. Exosomal miR-574-5p promoted osteoclastogenesis by targeting BMP2. Moreover, exosomes facilitated osteoclast differentiation, promoting bone metastasis by regulating miR-574-3p in vivo. In conclusion, liver cancer cell-derived exosomal miR-574-5p promoted osteoclastogenesis by regulating BMP2, thereby promoting bone metastasis in vivo. The findings suggest that liver cancer cell-released exosomes are the potential therapeutic approach for bone metastatic liver cancer. DATA AVAILABILITY STATEMENT: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Both live and heat-killed Bifidobacterium animalis J-12 alleviated oral ulcers in LVG golden Syrian hamsters by gavage by directly intervening in the intestinal flora structure.

Live and heat-killed Bifidobacterium has been proven to have anti-inflammatory and antioxidant effects. In this study, we evaluated the effects of live and heat-killed Bifidobacterium animalis J-12 (J-12) on the oral ulceration of LVG golden Syrian hamsters after buccal membrane injection with methyl viologen dichloride. Results showed that interleukin-1ß, glutathione, and malondialdehyde in serum were downregulated by the gavage of live and heat-killed J-12 bacteria. The J-12 live and heat-killed bacteria can reduce the expression of matrix metalloproteinase-9 by reducing the expression of nuclear factor kappa-B, thus reducing the expression of anti-inflammatory factors lipoxin A4 and prostaglandin E2. Reducing the expression of caspase-3 and adenosine diphosphate ribose polymerase resulted in a reduction of ulcer tissue DNA damage. In addition, regulating the structure of the intestinal flora prevented the process of oral ulcer formation. This study shows that J-12 can reduce the risk of oral ulcer formation while also having a positive effect on inhibiting existing oral ulcer growth.

Efficacy of transcranial direct current stimulation on postoperative delirium in elderly patients undergoing lower limb major arthroplasty: A randomized controlled trial.

BACKGROUND: Postoperative delirium (POD) is a common and severe postoperative complication in elderly patients undergoing major surgery linked to increased morbidity and mortality. It is reported that transcranial direct current stimulation (tDCS) effectively enhances cognitive function and improves impaired consciousness. OBJECTIVE: This study aimed to evaluate the efficacy of tDCS on POD in elderly patients undergoing lower limb major arthroplasty, including total hip arthroplasty (THA) or total knee arthroplasty (TKA). METHODS: Patients aged ≥65 years scheduled for THA or TKA were randomly assigned to receive 2 mA tDCS for 20 min active-tDCS (n = 61) or sham-tDCS (n = 61). The primary outcome was the incidence of POD during the first 3 postoperative days. RESULTS: All 122 patients (median age, 70 years; 80 women [65.6%]) completed the trial. The incident delirium risk was 4.9% (n = 3) vs. 19.7% (n = 12) in active-tDCS and sham-tDCS groups, respectively (relative risk, 0.250; 95% CI, 0.074 to 0.842; P = 0.013). Compared to the sham-tDCS group, the anxiety and depression scores of patients in the active-tDCS group were lower at 2 h and one day after surgery (P < 0.001 for each), and pain scores of patients in the active-tDCS group were lower during the first three days after surgery (P < 0.05). CONCLUSION: One session of anodal tDCS over the left dorsolateral prefrontal cortex may decrease the incidence of POD in elderly patients undergoing lower limb major arthroplasty.

Electroacupuncture restores intestinal mucosal barrier through TLR4/NF-κB p65 pathway in functional dyspepsia-like rats.

Functional dyspepsia (FD) is a common functional gastrointestinal disorder with high morbidity. Electroacupuncture (EA) has been applied to treat FD for a long time. The aim of this study was to investigate the effects of EA and its mechanism about intestinal mucosal barrier in rodent model of FD. Male Sprague-Dawley rats were randomly divided into the control group and the model group. Then, the rats in model group were established to the FD model by multifactor interventions. In Experiment 1, qualified FD-like rats were randomly divided into three groups: FD, EA, and acupuncture (AP) groups. The interventions of EA and AP lasted 14 days, food intake, and body weight were recorded every 5 days. In Experiment 2, qualified FD-like rats were randomly divided into five groups: FD, EA, AP, EA + TAK242, and TAK242 groups. The interventions of EA and AP lasted 14 days, while TAK242 injection continued for 6 days. The rats were sacrificed for the measurement of serum Interleukin- 6 (IL-6) and Tumor necrosis factor-α (TNF-α) assayed by ELISA. Western blotting was used to assess the expression of TLR4, Myd88, NF-κB p65, p-NF-κB p65, TRAF6, ZO-1, and occludin in the duodenum. The transmission electron microscope was used to observe the ultrastructure of intestinal epithelial cells. Compared with the rats in the group FD, the rats in EA group had significantly increase of body weight, food intake, and protein expressions of ZO-1 and occludin, while expressions of TLR4, Myd88, NF-κB p65, p-NF-κB p65, TRAF6 in the duodenum and IL-6, and TNF-α in serum were decreased. The EA + TAK242 treatment had similar effects to the EA treatment but with increased potency; compared with EA, AP showed similar but reduced effects. Our data demonstrated that EA is more effective than AP in improving intestine mucosal barrier. The possible mechanisms of EA may involve the TLR4/NF-κB p65 pathway.

The A-to-I editing of KPC1 promotes intrahepatic cholangiocarcinoma by attenuating proteasomal processing of NF-κB1 p105 to p50.

BACKGROUND: Aberrant RNA editing of adenosine-to-inosine (A-to-I) has been linked to multiple human cancers, but its role in intrahepatic cholangiocarcinoma (iCCA) remains unknown. We conducted an exome-wide investigation to search for dysregulated RNA editing that drive iCCA pathogenesis. METHODS: An integrative whole-exome and transcriptome sequencing analysis was performed to elucidate the RNA editing landscape in iCCAs. Putative RNA editing sites were validated by Sanger sequencing. In vitro and in vivo experiments were used to assess the effects of an exemplary target gene Kip1 ubiquitination-promoting complex 1 (KPC1) and its editing on iCCA cells growth and metastasis. Crosstalk between KPC1 RNA editing and NF-κB signaling was analyzed by molecular methods. RESULTS: Through integrative omics analyses, we revealed an adenosine deaminases acting on RNA 1A (ADAR1)-mediated over-editing pattern in iCCAs. ADAR1 is frequently amplified and overexpressed in iCCAs and plays oncogenic roles. Notably, we identified a novel ADAR1-mediated A-to-I editing of KPC1 transcript, which results in substitution of methionine with valine at residue 8 (p.M8V). KPC1 p.M8V editing confers loss-of-function phenotypes through blunting the tumor-suppressive role of wild-type KPC1. Mechanistically, KPC1 p.M8V weakens the affinity of KPC1 to its substrate NF-κB1 p105, thereby reducing the ubiquitinating and proteasomal processing of p105 to p50, which in turn enhances the activity of oncogenic NF-κB signaling. CONCLUSIONS: Our findings established that amplification-driven ADAR1 overexpression results in overediting of KPC1 p.M8V in iCCAs, leading to progression via activation of the NF-κB signaling pathway, and suggested ADAR1-KPC1-NF-κB axis as a potential therapeutic target for iCCA.

The interfacial and assembly properties of in situ producing silica nanoparticle at oil-water interface.

In multiphase materials, structured fluid-fluid interfaces can provide mechanical resistance against destabilization, applicable for conformance control, Pickering emulsion, liquid 3D printing and molding, etc. Currently all research prepare the particle-ladened fluid-fluid interfaces by dispersing ex situ acquired particles to the immiscible interface, which limits their application in the harsh environment, such as oil reservoir which can impair particle stability and transport ability. Here, we investigated the interfacial and assembly properties of the interface where SiO2 nanoparticles (NPs) were in situ produced. The experimental results show that ammonia as catalyst could accelerate the processes of silica NPs formation as well as the interfacial tension (IFT) evolution. High temperature could not accelerate the reaction processes to achieve the lowest equilibrium IFT, but it induced the sine-wave IFT evolution curves regardless of the presence of ammonia. The equilibrium IFTs corresponded to the saturation states of interfaces trapping with SiO2 NPs, while the sine-wave fluctuating patterns of IFT were attributed to the alternating transition between interfacial jammed and unjammed states changing along with the reaction process. Silica NPs diffusing into aqueous phase with high salinity also showed good stability, due to the abundant surface decoration with in situ anchored organic species.