Development and Validation of a Machine Learning Model for Bone Metastasis in Prostate Cancer: Based on Inflammatory and Nutritional Indicators.

OBJECTIVE: To establish a predictive model for prostate cancer bone metastasis utilizing multiple machine learning algorithms. METHODS: Retrospective analysis of the clinical data of prostate cancer initially diagnosed in the Department of Urology of Gansu Provincial People's Hospital from June 2017 to June 2022. Logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) are used to jointly screen the model features. The filtered features are incorporated into algorithms including LR, random forest (RF), extreme gradient boosting (XGBoost), naive Bayes (NB), k-nearest neighbor (KNN), and decision tree (DT), to develop prostate cancer bone metastasis models. RESULTS: A total of 404 patients were finally screened. Gleason score, T stage, N stage, PSA, and ALP were used as features for modeling. The average AUC of the 5-fold cross-validation for each machine learning model in the training set is as follows: LR (AUC=0.9054), RF (AUC=0.9032), NB (AUC=0.8961), KNN (AUC=0.8704), DT (AUC=0.8526), XGBoost (AUC=0.8066). The AUC of each machine learning model in the test set is KNN (AUC=0.9390, 95%CI: 0.8760-1), RF (AUC=0.9290, 95%CI: 0.8718-0.9861), NB (AUC=0.9268, 95%CI: 0.8615-0.9920), LR (AUC=0.9212, 95%CI: 0.8506-0.9917), XGBoost (AUC=0.8292, 95%CI: 0.7442-0.9141), DT (AUC=0.8057, 95%CI: 0.7100-0.9014). A comprehensive evaluation showed that LR performed well in interpretability and clinical applications. CONCLUSION: A bone metastasis model of prostate cancer was established, and it was observed that indicators such as inflammation and nutrition had a weak correlation with bone metastasis.

Dietary iron intake and its impact on osteopenia/osteoporosis.

BACKGROUND: Osteoporosis is a prevalent condition characterized by low bone density and increased risk of fractures, resulting in a significant healthcare burden. Previous research has suggested that serum ferritin levels may be related to the risk of developing osteoporosis. The aim of this study was to investigate the relationship between dietary iron intake and the development of osteoporosis. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018, a total of 11,690 adults aged over 20 were evaluated. Bone mineral density (BMD) measurements of the femoral neck and lumbar spine were used to assess osteoporosis and osteopenia. Dietary iron intake was determined using food intake interviews and the Food and Nutrient Database for Dietary Studies. Logistic regression models were applied to investigate the association between dietary iron consumption and osteopenia and osteoporosis. RESULTS: After adjusting for sociodemographic factors, compared with those who had the first quartile (Q1) of dietary iron intake, the odds ratio (OR) for osteopenia across the quartiles of dietary iron intake levels was 0.88 (95%CI: 0.79-0.98), 0.80 (95%CI: 0.72-0.89), and 0.74 (95%CI: 0.67-0.83) for Q2, Q3, and Q4, respectively. And the OR for osteoporosis across the quartiles of dietary iron intake levels was 1.00, 0.77 (95%CI: 0.50-1.19), 0.54 (95%CI: 0.34-0.89), and 0.83 (95%CI: 0.54-1.29) for Q1, Q2, Q3, and Q4, respectively. Notably, the observed association was significant among females but not males. CONCLUSION: The risk of osteopenia/osteoporosis in females decreases with a moderate increase in dietary iron consumption. For females to preserve bone health, moderately increasing their dietary iron intake without overindulging should be seen as a key approach. Our study provides useful insights for developing dietary strategies to prevent and manage osteoporosis in vulnerable populations.

Predictive role of pretreatment skeletal muscle mass index for long-term survival of bladder cancer patients: A meta-analysis.

PURPOSE: To identify the predictive role of pretreatment skeletal muscle mass index (SMI) for long-term survival of bladder cancer patients. METHODS: Several databases were searched for studies investigating the relationship between pretreatment SMI and prognosis in bladder cancer. The overall survival (OS) and cancer-specific survival (CSS) were defined as primary and secondary outcomes, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined. RESULTS: Nine studies involving 1476 cases were included. The results demonstrated that a lower pretreatment SMI was significantly related to poorer OS (HR = 1.56, 95% CI: 1.33-1.82, P<0.001) and subgroup analysis based on thresholds of SMI revealed similar results. Besides, pretreatment SMI was also obviously related to CSS (HR = 1.75, 95% CI: 1.36-2.25, P<0.001). CONCLUSION: Lower pretreatment SMI was associated with worse long-term survival of bladder cancer patients.

SurgSmart: an artificial intelligent system for quality control in laparoscopic cholecystectomy: an observational study.

BACKGROUND: The rate of bile duct injury in laparoscopic cholecystectomy (LC) continues to be high due to low critical view of safety (CVS) achievement and the absence of an effective quality control system. The development of an intelligent system enables the automatic quality control of LC surgery and, eventually, the mitigation of bile duct injury. This study aims to develop an intelligent surgical quality control system for LC and using the system to evaluate LC videos and investigate factors associated with CVS achievement. MATERIALS AND METHODS: SurgSmart, an intelligent system capable of recognizing surgical phases, disease severity, critical division action, and CVS automatically, was developed using training datasets. SurgSmart was also applied in another multicenter dataset to validate its application and investigate factors associated with CVS achievement. RESULTS: SurgSmart performed well in all models, with the critical division action model achieving the highest overall accuracy (98.49%), followed by the disease severity model (95.45%) and surgical phases model (88.61%). CVSI, CVSII, and CVSIII had an accuracy of 80.64, 97.62, and 78.87%, respectively. CVS was achieved in 4.33% in the system application dataset. In addition, the analysis indicated that surgeons at a higher hospital level had a higher CVS achievement rate. However, there was still considerable variation in CVS achievement among surgeons in the same hospital. CONCLUSIONS: SurgSmart, the surgical quality control system, performed admirably in our study. In addition, the system's initial application demonstrated its broad potential for use in surgical quality control.

Literature review, report, and analysis of genotype and clinical phenotype of a rare case of ulnar-mammary syndrome.

Objective: The clinical characteristics of Ulnar-mammary syndrome (UMS) caused by mutations in TBX3 (T-Box transcription factor 3) were studied and the correlation between genotype and clinical phenotype were analyzed to improve awareness and early diagnosis of the disease. Methods: The clinical data of a boy aged 13 years and 5 months with left forearm deformity and growth retardation as the main features were analyzed. Genomic exon detection was performed, and the results were verified by Sanger sequencing. Simultaneously, we performed literature review to analyze the correlation between clinical phenotypes and genotypes. Results: The clinical manifestations in the child were short stature, ulnar hypoplasia of the forearm, hypohidrosis, retracted nipple, micropenis, and cryptorchidism. Laboratory examination revealed hyperthyroidism, growth hormone deficiency, and hypogonadotropic hypogonadism. Imaging results displayed delayed bone age, small pituitary gland, and persistence of Rathke's cleft cyst. The results of the exome sequencing revealed the deletion of AGA at positions 1121-1,124 of TBX3, which resulted in a frameshift mutation (c.1121-1124del AGAG; pGlu374fs). According to the American College of Medical Genetics (ACMG) assessment, the mutation is a pathogenic variant. A definitive diagnosis of UMS was made on the basis of the clinical phenotype of the patient. The Chinese and English literature were reviewed to analyze the correlation between TBX3 genotype and clinical phenotype. Conclusion: UMS is a rare hereditary disease caused by mutations in TBX3. There is significant clinical heterogeneity associated with the variants of this gene. To our knowledge, this mutation site in TBX3 has been reported for the first time, thereby expanding the mutation spectrum of this gene.

Prognostic Role of Pretreatment Geriatric Nutritional Risk Index in Colorectal Cancer Patients: A Meta-Analysis.

To identify the prognostic value of the pretreatment geriatric nutritional risk index (GNRI) in colorectal cancer. Several electronic databases were searched up to March 15, 2022, for relevant studies. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), respectively. The hazard ratios (HRs) with 95% confidence intervals (CIs) were combined. Bess's funnel plot and Egger's test were conducted to detect publication bias, and the trim-and-fill method was performed to identify potentially unpublished papers and their impacts on the overall results. Nine studies from Japan and China involving 3440 participants were enrolled in the current meta-analysis. The pooled results indicated that a low pretreatment GNRI was significantly associated with poorer OS (HR = 2.28, 95% CI: 1.69-3.07, P < 0.001; I2=63.5%, Pheterogeneity=0.005) and DFS (HR = 1.62, 95% CI: 1.35-1.96, P < 0.001; I2=46.4%, Pheterogeneity=0.114). Subgroup analysis stratified by country and treatment showed similar results. Significant publication bias was manifested by the asymmetric Begg's funnel plot and P = 0.012 of Egger's test, but three potentially unpublished studies did not have a significant impact on the overall results. A lower pretreatment GNRI was a novel prognostic risk factor for Japanese and Chinese colorectal cancer patients.

The efficacy of continuing nursing interventions on intraoperative pressure ulcer-related complications in breast cancer patients: systematic review and meta-analysis.

Background: This study systematically reviewed the effects of continuous nursing intervention on intraoperative pressure ulcers (PUs) and related complications in breast cancer patients. The effectiveness of continuous nursing intervention for intraoperative pressure ulcers related complications in breast cancer patients is highly controversial. Therefore, it is necessary to systematically review and address this issue by means of meta-analysis. Methods: By searching the Cochrane Library, PubMed, Web of Science, Embase, and Chinese Biomedical Literature Database (CBM) were screened. Quality evaluation and data extraction were performed for the included studies, and meta-analysis was performed for the included RCTs using Review Manager 5.2 software. Literature was included in strict compliance with the PICOS principle, and bias risk was analyzed by t-test and funnel plot. Results: A total of 1,431 patients were enrolled in 9 studies, and meta-analysis showed that there was a significant statistical difference between the experimental group and the control group in the incidence of PUs [odds ratio (OR) =0.18, 95% confidence interval (95% CI): 0.13-0.24, P<0.00001], the Braden pressure ulcer risk score after nursing [mean difference (MD) =2.64, 95% CI: 1.47-3.81, P<0.0001], and the quality of life after nursing (MD =9.76, 95% CI: 6.82-12.69, P<0.00001). Discussion: Continuous care can reduce the incidence of PUs in patients with advanced breast cancer, reduce the severity of wounds in the healing process of PUs, and improve the knowledge of PUs in patients with advanced breast cancer risk.

Surgesture: a novel instrument based on surgical actions for objective skill assessment.

BACKGROUND: Due to varied surgical skills and the lack of an efficient rating system, we developed Surgesture based on elementary functional surgical gestures performed by surgeons, which could serve as objective metrics to evaluate surgical performance in laparoscopic cholecystectomy (LC). METHODS: We defined 14 LC basic Surgestures. Four surgeons annotated Surgestures among LC videos performed by experts and novices. The counts, durations, average action time, and dissection/exposure ratio (D/E ratio) of LC Surgestures were compared. The phase of mobilizing hepatocystic triangle (MHT) was extracted for skill assessment by three professors using a modified Global Operative Assessment of Laparoscopic Skills (mGOALS). RESULTS: The novice operation time was significantly longer than the expert operation time (58.12 ± 19.23 min vs. 26.66 ± 8.00 min, P < 0.001), particularly during MHT phase. Novices had significantly more Surgestures than experts in both hands (P < 0.05). The left hand and inefficient Surgesture of novices were dramatically more than those of experts (P < 0.05). The experts demonstrated a significantly higher D/E ratio of duration than novices (0.79 ± 0.37 vs. 2.84 ± 1.98, P < 0.001). The counts and time pattern map of LC Surgestures during MHT demonstrated that novices tended to complete LC with more types of Surgestures and spent more time exposing the surgical scene. The performance metrics of LC Surgesture had significant but weak associations with each aspect of mGOALS. CONCLUSION: The newly constructed Surgestures could serve as accessible and quantifiable metrics for demonstrating the operative pattern and distinguishing surgeons with various skills. The association between Surgestures and Global Rating Scale laid the foundation for establishing a bridge to automated objective surgical skill evaluation.

Core Decompression Prevents Progression of Asymptomatic Type C Osteonecrosis of Femoral Head According to the Japanese Investigation Committee Classification: A Retrospective Study.

OBJECTIVE: To evaluate whether core decompression could prevent progression of asymptomatic type C osteonecrosis of the femoral head (ONFH) according to the Japanese Investigation Committee (JIC) classification. METHODS: This retrospective cohort study included 124 hips (117 patients) with asymptomatic type C ONFH. Seventy-one hips (67 patients) received core decompression (core decompression group) and 53 hips (50 patients) received no surgical treatment (control group). Clinical and radiological follow-up was conducted at 6 and 12 months, then annually until 5 years. Clinical outcomes were evaluated in terms of the Oxford hip score and UCLA Activity Level rating. Radiological outcomes were evaluated using X-ray and magnetic resonance imaging. Survival analysis was performed based on collapse of the femoral head as the first endpoint and total hip arthroplasty (THA) as the second endpoint. RESULTS: There were no significant differences in clinical outcomes between the core decompression group and the control group within 2 years after surgery. Patients in the core decompression group had significantly better Oxford hip score and UCLA Activity Level from year 3 to the end of follow-up (P < 0.05). In year 5, the absolute difference in Oxford hip score (5.3 points) exceeded the reported minimal clinically important difference (MCID, 5.2 points). In years 3-5, the absolute difference in UCLA Activity Level rating (0.95 points, 0.95 points, and 0.99 points, respectively) exceeded the reported MCID (0.92 points). By 5-year follow-up, significantly fewer patients in the core decompression group had experienced femoral head collapse (40.8% vs 62.3%, P = 0.011) or received THA (26.8% vs 45.3%, p = 0.022). CONCLUSIONS: Core decompression can prevent progression of asymptomatic type C ONFH according to the JIC classification, leading to better medium-term hip function and activity levels than no surgical treatment. Core decompression is recommended for early intervention against asymptomatic type C ONFH.

Investigation of the Quality of Recovery of Surgical Patients Based on the Chinese Version of the Quality of Recovery-15 Survey, a Cross-Sectional Study.

PURPOSE: The quality of recovery (QoR) is an important indicator of a patient's health status in the early postoperative period. Despite its importance, the QoR from the patient's perspective is often neglected in clinical practice. This study was performed to survey and determine the QoR of surgical patients from their own subjective perspective and to provide a reference for the targeted postoperative care of surgical patients in the future. DESIGN: A descriptive and cross-sectional study. METHODS: The Chinese version of the Quality of Recovery-15 (QoR-15) scale was used to survey the QoR of 503 surgical patients in 20 surgical wards from 17 surgical departments of a large tertiary hospital in Sichuan Province, China. A questionnaire survey was administered to each patient before and after the operation, and the scores were compared. FINDINGS: There were no significant differences in "feeling worried or anxious" and "feeling sad or depressed" between the preoperative and postoperative periods (P > 0.05). The postoperative scores for the other items were significantly lower than the preoperative scores. The total postoperative QoR-15 score was significantly lower than the total preoperative score (P < 0.001). CONCLUSIONS: The QoR-15 scores of surgical patients were lower after the surgery than before, and patients still needed care after discharge. Therefore, due to the gradual shortening of the length of stay (LOS) of surgical patients, it is necessary for hospitals to construct a complete surgical patient transitional care process to meet the needs of patients after discharge and promote patient rehabilitation.

Walnut ointment promotes full-thickness burning wound healing: role of linoleic acid

Purpose: To investigate the active ingredients of walnut ointment (WO) and its mechanism in repairing wounds. Methods: The ingredients of WO were detected by gas chromatography­mass spectrometry. The effect of linoleic acid (LA) was tested by in vitro Alamar Blue (AB) reagent. Image J software, histological and immunohistochemical analysis were used to confirm the healing effect of LA in the porcine skin model. The animals were euthanized after the experiment by injection of pentobarbital sodium. Results: LA, 24% in WO, promotes keratinocytes and fibroblasts proliferation, which were 50.09% and 15.07% respectively higher than control (p < 0.05). The healing rate of the LA group (96.02% ± 2%, 98.58% ± 0.78%) was higher than the saline group (82.11% ± 3.37%, 88.72% ± 1.73%) at week 3 and week 4 (p < 0.05). The epidermal thickness of the LA was 0.16 ± 0.04 mm greater and the expression of the P63 and CK10 proteins was stronger in the LA group than the control (p < 0.05). Conclusions: LA, which is the main components in WO can promote full-thickness burning wounds (FBWs) by stimulating cell proliferation and differentiation.

Is three-dimensional-printed custom-made ultra-short stem with a porous structure an acceptable reconstructive alternative in peri-knee metaphysis for the tumorous bone defect?

BACKGROUND: Long-lasting reconstruction after extensive resection involving peri-knee metaphysis is a challenging problem in orthopedic oncology. Various reconstruction methods have been proposed, but they are characterized by a high complication rate. The purposes of this study were to (1) assess osseointegration at the bone implant interface and correlated incidence of aseptic loosening; (2) identify complications including infection, endoprosthesis fracture, periprosthetic fracture, leg length discrepancy, and wound healing problem in this case series; and (3) evaluate the short-term function of the patient who received this personalized reconstruction system. METHODS: Between September 2016 and June 2018, our center treated 15 patients with malignancies arising in the femur or tibia shaft using endoprosthesis with a 3D-printed custom-made stem. Osseointegration and aseptic loosening were assessed with digital tomosynthesis. Complications were recorded by reviewing the patients' records. The function was evaluated with the 1993 version of the Musculoskeletal Tumor Society (MSTS-93) score at a median of 42 (range, 34 to 54) months after reconstruction. RESULTS: One patient who experienced early aseptic loosening was managed with immobilization and bisphosphonates infusion. All implants were well osseointegrated at the final follow-up examination. There are two periprosthetic fractures intraoperatively. The wire was applied to assist fixation, and the fracture healed at the latest follow-up. Two patients experienced significant leg length discrepancies. The median MSTS-93 score was 26 (range, 23 to 30). CONCLUSIONS: A 3D-printed custom-made ultra-short stem with a porous structure provides acceptable early outcomes in patients who received peri-knee metaphyseal reconstruction. With detailed preoperative design and precise intraoperative techniques, the reasonable initial stability benefits osseointegration to osteoconductive porous titanium, and therefore ensures short- and possibly long-term durability. Personalized adaptive endoprosthesis, careful intraoperative operation, and strict follow-up management enable effective prevention and treatment of complications. The functional results in our series were acceptable thanks to reliable fixation in the bone-endoprosthesis interface and an individualized rehabilitation program. These positive results indicate this device series can be a feasible alternative for critical bone defect reconstruction. Nevertheless, longer follow-up is required to determine whether this technique is superior to other forms of fixation.

Autologous Osteochondral Graft for Early Posttraumatic Arthritis of Tibiotalar Joints After Comminuted Pilon Fractures in Young Patients.

BACKGROUND: Posttraumatic arthritis of tibiotalar joints after AO/OTA type C3 pilon fractures, especially in young patients with a significant osteochondral defect in the tibial plafond joint surface, is a challenging situation. We report a joint-preserving technique using autologous osteochondral graft in combination with ankle distraction and supramalleolar osteotomy (SMOT), if necessary, to improve its outcome. METHODS: Seventeen patients with an average age of 32.1 years with Takakura grade 1 to 3A posttraumatic arthritis of the tibiotalar joint after AO/OTA type C3 pilon fractures received osteochondral autograft transplantation, ankle distraction, and SMOT, when supramalleolar malalignment was present, between February 2010 and November 2015. The visual analog scale (VAS), Short-Form 36 (SF-36) score, American Orthopaedic Foot & Ankle Society (AOFAS) score, and ankle range of motion were used for outcome analysis. Radiographic assessment of any SMOT and the apparent joint space was performed. Fourteen patients were followed for an average of 18 months. RESULTS: The VAS, SF-36, and AOFAS scores as well as the ankle range of motion all improved significantly at the last follow-up after the surgery (P < .01). No deep surgical site infection, donor site complication, nonunion, osteochondral block loosening, or resorption was noted. No secondary arthrodesis was needed at the end of follow-up. CONCLUSION: Autologous osteochondral graft transplantation in combination with ankle distraction and SMOT was a promising joint-preserving technique for early posttraumatic arthritis of tibiotalar joint after severe pilon fractures in young patients. LEVEL OF EVIDENCE: Level IV, case series.

Effect of Lactoferrin on the Expression Profiles of Long Non-coding RNA during Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells.

Lactoferrin (LF) has demonstrated stimulation of osteogenic differentiation of mesenchymal stem cells (MSCs). Long non-coding RNAs (lncRNAs) participate in regulating the osteogenic differentiation processes. However, the impact of LF on lncRNA expression in MSC osteogenic differentiation is poorly understood. Our aim was to investigate the effects of LF on lncRNAs expression profiles, during osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), by RNA sequencing. A total number of 1331 putative lncRNAs were identified in rBMSCs during osteogenic differentiation in the study. LF influenced the expression of 120 lncRNAs (differentially expressed lncRNAs [DELs], Fold change > 1.5 or < -1.5; p < 0.05) in rBMSCs on day 14 of osteogenic differentiation, consisted of 60 upregulated and 60 down-regulated. Furthermore, the potential functions of DELs were of prediction by searching their target cis- and trans-regulated protein-coding genes. The bioinformatic analysis of DELs target gene revealed that LF led to the disfunction of transforming growth factor beta stimulus (TGF-ß) and positive regulation of I-κappa B kinase/NF-κappa B signaling pathway, which may relate to osteogenic differentiation of rBMSCs. Our work is the first profiling of lncRNA in osteogenic differentiation of rBMSCs induced by LF, and provides valuable insights into the potential mechanisms for LF promoting osteogenic activity.

Exendin-4 enhances proliferation of senescent osteoblasts through activation of the IGF-1/IGF-1R signaling pathway.

A growing body of evidence indicates that treatment with glucagon-like peptide-1 (GLP-1) receptor agonists can be beneficial for patients with osteoporosis. However, the underlying mechanism by which GLP-1 receptor agonists improve osteoporosis remains unclear. In this study, we assessed the anti-osteoporosis effects of Exendin-4, a highly potent GLP-1 receptor agonist, using a rat senescent osteoblast model. We found that Exendin-4 improved proliferation of senescent osteoblasts, as indicated by MTT assay and ALP activity detection. RT-qPCR revealed that Exendin-4 up-regulated the expression of bone metabolism genes (OPG, RANKL, BGP) and down-regulated the expression of aging-related genes (p16, p21, p53). Meanwhile, we observed a sustained increase in IGF-1 receptor (IGF-1R) expression, and not GLP-1 receptor (GLP-1R) expression, in senescent osteoblasts treated with Exendin-4. Furthermore, intervention with Exendin-4 in senescent osteoblasts increased IGF-1, p-PI3K, and p-Akt protein levels, as shown by western blot analysis. Finally, downregulation of IGF-1 by RNAi inhibited the anti-osteoporosis effects of Exendin-4, which is associated with the IGF-1/PI3K/Akt signaling pathway. In summary, these results indicate that the GLP-1 receptor agonist Exendin-4 promotes proliferation of senescent osteoblasts by up-regulating IGF-1R expression and activating the IGF-1/PI3K/Akt signaling pathway, thereby preventing senile osteoporosis.

The In Vitro Protective Role of Bovine Lactoferrin on Intestinal Epithelial Barrier.

The intestinal epithelial barrier plays a key protective role in the gut lumen. Bovine lactoferrin (bLF) has been reported to improve the intestinal epithelial barrier function, but its impact on tight junction (TJ) proteins has been rarely described. Human intestinal epithelial crypt cells (HIECs) were more similar to those in the human small intestine, compared with the well-established Caco-2 cells. Accordingly, both HIECs and Caco-2 cells were investigated in this study to determine the effects of bioactive protein bLF on their growth promotion and intestinal barrier function. The results showed that bLF promoted cell growth and arrested cell-cycle progression at the G2/M-phase. Moreover, bLF decreased paracellular permeability and increased alkaline phosphatase activity and transepithelial electrical resistance, strengthening barrier function. Immunofluorescence, western blot and quantitative real-time polymerase chain reaction revealed that bLF significantly increased the expression of three tight junction proteins-claudin-1, occludin, and ZO-1-at both the mRNA and protein levels, and consequently strengthened the barrier function of the two cell models. bLF in general showed higher activity in Caco-2 cells, however, HIECs also exhibited desired responses to barrier function. Therefore, bLF may be incorporated into functional foods for treatment of inflammatory bowel diseases which are caused by loss of barrier integrity.

Recurrent nonsevere hypoglycemia exacerbates imbalance of mitochondrial homeostasis leading to synapse injury and cognitive deficit in diabetes.

Recurrent nonsevere hypoglycemia (RH) can lead to cognitive dysfunction in patients with diabetes, although the involved mechanisms remain unclear. Here, we aimed to investigate the mechanism underlying RH-induced cognitive deficits with a focus on mitochondrial homeostasis. To establish a model that mimicked RH in patients with type 1 diabetes (T1DM) receiving insulin therapy, streptozotocin-induced mice with T1DM were subjected to recurrent, twice-weekly insulin injections over 4 wk. We found that RH disrupted the mitochondrial fine structure, reduced the number of mitochondria, and upregulated the expression of mitochondrial dynamics and mitophagy markers, including dynamin-related protein 1 (Drp1), Bcl-2/adenovirus E1B 19-kDa-interacting protein-3 (BNIP3), and microtubule-associated protein 1 light-chain 3 (LC3) in the hippocampus of T1DM mice. Moreover, RH and chronic hyperglycemia synergistically promoted the production of reactive oxygen species, impaired mitochondrial membrane potential, and suppressed mitochondrial energy metabolism. Under diabetic conditions, RH also altered the synaptic morphology and reduced the expression of synaptic marker proteins. Long-term recognition memory and spatial memory, assessed with the Morris water maze test, were also impaired. However, these effects were largely prevented by mitochondrial division inhibitor 1, a potent and selective Drp1 inhibitor. Thus, it appears that RH exacerbates the imbalance of mitochondrial homeostasis, leading to synapse injury and cognitive deficits in diabetes. The adjustment of mitochondrial homeostasis could serve as an effective neuroprotective approach when addressing low blood sugar conditions.

Repellence of Common Tobacco Flavorants on Lasioderma serricorne (Coleoptera: Anobiidae).

The cigarette beetle, Lasioderma serricorne (F.) (Coleoptera: Anobiidae) is a destructive pest species of tobacco. Olfactory repellents derived from permitted tobacco flavorants have the advantage of not adversely effecting tobacco flavor. Among 12 test compounds, neral exhibited the strongest repellent effect. Among six binary blends prepared, three blends (neral + ethyl cinnamate, neral + cinnamaldehyde, and neral + methyl cinnamate) evoked the strongest repellent response. The interactions between neral and any one of the cinnamic acid derivatives were additive, and the interactions between neral and the cinnamic acid derivatives were antagonistic. In a 32-d tobacco barn bioassay, neral + cinnamaldehyde (embedded in 0.5% agaropectin) showed the strongest repellent effect with a persistence of at least 30 d. The binary blend of two tobacco additives (neral and cinnamaldehyde) appears promising as a repellent for controlling cigarette beetles in tobacco barns.

Development of a stable biosensor based on a SiO2 nanosheet-Nafion-modified glassy carbon electrode for sensitive detection of pesticides.

SiO(2) nanosheets (SNS) have been prepared by a chemical method using montmorillonite as raw material and were characterized by scanning electron microscopy and X-ray diffraction. SiO(2) nanosheet-Nafion nanocomposites with excellent conductivity, catalytic activity, and biocompatibility provided an extremely hydrophilic surface for biomolecule adhesion. Chitosan was used as a cross-linker to immobilize acetylcholinesterase (AChE), and Nafion was used as a protective membrane to efficiently improve the stability of the AChE biosensor. The AChE biosensor showed favorable affinity for acetylthiocholine chloride and catalyzed the hydrolysis of acetylthiocholine chloride with an apparent Michaelis-Menten constant of 134 µM to form thiocholine, which was then oxidized to produce a detectable and fast response. Based on the inhibition by pesticides of the enzymatic activity of AChE, detection of the amperometric response from thiocholine on the biosensor is a simple and effective way to biomonitor exposure to pesticides. Under optimum conditions, the biosensor detected methyl parathion, chlorpyrifos, and carbofuran at concentrations ranging from 1.0 × 10(-12) to 1 × 10(-10) M and from 1.0 × 10(-10) to 1 × 10(-8) M. The detection limits for methyl parathion, chlorpyrifos, and carbofuran were 5 × 10(-13) M. The biosensor developed exhibited good sensitivity, stability, reproducibility, and low cost, thus providing a new promising tool for analysis of enzyme inhibitors.