A ratiometric, colorimetric fluorescent probe with a large emission shift for the rapid detection of diethyl chlorophosphate.

A new ratiometric and colorimetric probe (SWJT-16) based on the isophorone skeleton to detect diethyl chlorophosphite (DCP), a nerve agent mimic, was designed and synthesized. SWJT-16 underwent a nucleophilic substitution reaction with DCP in DMF, leading to a large emission shift (Δλem = 174 nm) accompanied by a significant color change from blue to yellow under visible light. All these changes occurred within 6 seconds, faster than those of most reported ratiometric fluorescent probes for DCP. Furthermore, SWJT-16 was successfully employed to monitor gaseous DCP.

Hyperglycemia Aggravates Periodontitis via Autophagy Impairment and ROS-Inflammasome-Mediated Macrophage Pyroptosis.

Macrophage pyroptosis drives the secretion of IL-1ß, which has been recently reported to be a featured salivary biomarker for discriminating periodontitis in the presence of diabetes. This study aimed to explore whether macrophage pyroptosis plays a role in the development of diabetes mellitus-periodontitis, as well as potential therapeutic strategies. By establishing a model of experimental diabetes mellitus-periodontitis in rats, we found that IL-1ß and gasdermin D were highly expressed, leading to aggravated destruction of periodontal tissue. MCC950, a potent and selective molecule inhibitor of the NLRP3 inflammasome, effectively inhibited macrophage pyroptosis and attenuated alveolar bone losses in diabetes mellitus-periodontitis. Consistently, in vitro, high glucose could induce macrophage pyroptosis and thus promoted IL-1ß production in macrophages stimulated by lipopolysaccharide. In addition, autophagy blockade by high glucose via the mTOR-ULK1 pathway led to severe oxidative stress response in macrophages stimulated by lipopolysaccharide. Activation of autophagy by rapamycin, clearance of mitochondrial ROS by mitoTEMPO, and inhibition of inflammasome by MCC950 could significantly reduce macrophage pyroptosis and IL-1ß secretion. Our study demonstrates that hyperglycemia promotes IL-1ß production and pyroptosis in macrophages suffered by periodontal microbial stimuli. Modulation of autophagy activity and specific targeting of the ROS-inflammasome pathway may offer promising therapeutic strategies to alleviate diabetes mellitus-periodontitis.

Constructing a Defined Starter for Multispecies Vinegar Fermentation via Evaluation of the Vitality and Dominance of Functional Microbes in an Autochthonous Starter.

Mature vinegar culture has usually been used as a type of autochthonous starter to rapidly initiate the next batch of acetic acid fermentation (AAF) and maintain the batch-to-batch uniformity of AAF in the production of traditional cereal vinegar. However, the vitality and dominance of functional microbes in autochthonous starters remain unclear, which hinders further improvement of fermentation yield and production. Here, based on metagenomic (MG), metatranscriptomic (MT), and 16S rRNA gene sequencings, 11 bacterial operational taxonomic units (OTUs) with significant metabolic activity (MT/MG ratio >1) and dominance (relative abundance >1%) were targeted in the autochthonous vinegar starter, all of which were assigned to 4 species (Acetobacter pasteurianus, Lactobacillus acetotolerans, L. helveticus, Acetilactobacillus jinshanensis). Then, we evaluated the successions and interactions of these 11 bacterial OTUs at different AAF stages. Last, a defined starter was constructed with 4 core species isolated from the autochthonous starter (A. pasteurianus, L. acetotolerans, L. helveticus, Ac. jinshanensis). The defined starter culture could rapidly initiate the AAF in a sterile or unsterilized environment, and similar dynamics of metabolites (ethanol, titratable acidity, acetic acid, lactic acid, and volatile compounds) and environmental indexes (temperature, pH) of fermentation were observed as compared with that of autochthonous starter (P > 0.05). This work provides a method to construct a defined microbiota from a complex system while preserving its metabolic function. IMPORTANCE Complex microorganisms are beneficial to the flavor formation in natural food fermentation, but they also pose challenges to the mass production of standardized products. It is attractive to construct a defined starter to rapidly initiate fermentation process and significantly improve fermentation yield. This study provides a comprehensive understanding of vital and dominant species in the autochthonous vinegar starter via multi-omics, and designs a defined microbial community for the efficient fermentation of cereal vinegar.

Notch/NICD/RBP-J signaling axis regulates M1 polarization of macrophages mediated by advanced glycation end products.

Advanced glycation end products (AGEs) aggregation and macrophages polarization are identified as the main factors contributing to bone diseases caused by aging or diabetes, such as senile or diabetic osteoporosis. Here, we aimed to elucidate the involvement and potential mechanism of AGEs in macrophages polarization and osteoclastogenesis. Firstly, AGEs-treated RAW264.7 macrophages were observed to up-regulate the release of nitric oxide (NO), the expression of M1-associated genes and the surface antigen marker CD86. The detection of osteoclast-related markers and TRAP staining revealed that the osteoclastogenic ability of M1 macrophages was markedly enhanced by AGEs. Further, AGEs were found to effectively activate the transduction of Notch signaling pathway and promote the nuclear translocation of NICD1. In addition, with the signals transduction of Notch pathway blocked by γ-secretase inhibitor DAPT and siRNA targeting silencing RBP-J, AGEs-induced M1 polarization was significantly mitigated. Collectively, we defined a critical role for AGEs in inducing M1 polarization and osteoclastogenesis of macrophages, and further identified Notch/NICD/RBP-J signaling axis as an essential mechanism regulating AGEs-mediated M1 polarization.

Reliability of cone beam CT for morphometry of nasolabial soft tissue in patients with skeletal class III malocclusion: A qualitative and quantitative analysis.

OBJECTIVE: To assess reliability of cone-beam CT (CBCT) for nasolabial soft tissue measurements in patients with skeletal class III malocclusion based on 3-dimensional (3D) facial scanner results. METHODS: CBCT and 3D facial scan images of 20 orthognathic patients are used in this study. Eleven soft tissue landmarks and 15 linear and angular measurements are identified and performed. For qualitative evaluation, Shapiro-Wilk test and Bland-Altman plots are applied to analyze the equivalence of the measurements derived from these two kinds of images. To quantify specific deviation of CBCT measurements from facial scanner, the latter is set as a benchmark, and mean absolute difference (MAD) and relative error magnitude (REM) for each variable are also calculated. RESULTS: Statistically significant differences are observed in regions of nasal base and lower lip vermilion between two methods. MAD value for all length measurements are less than 2 mm and for angular variables < 8°. The average MAD and REM for length measurements are 0.94 mm and 5.64%, and for angular measurements are 2.27° and 3.78%, respectively. CONCLUSIONS: The soft tissue results measured by CBCT show relatively good reliability and can be used for 3D measurement of soft tissue in the nasolabial region clinically.

Jinlida granules ameliorate the high-fat-diet induced liver injury in mice by antagonising hepatocytes pyroptosis.

CONTEXT: Jinlida (JLD) as a traditional Chinese medicine formula has been used to treat type 2 diabetes mellitus (T2DM) and studies have shown its anti-obesity effect. OBJECTIVE: To investigate the therapeutic effects of JLD in a mouse model of non-alcoholic fatty liver (NAFL). MATERIALS AND METHODS: C57BL/6J mice were divided into three groups and fed a low-diet diet (LFD), high-fat diet (HFD), or HFD + JLD (3.8 g/kg) for 16 weeks, respectively. The free fatty acids-induced lipotoxicity in HepG2 cells were used to evaluate the anti-pyroptotic effects of JLD. The pharmacological effects of JLD on NAFL were investigated by pathological examination, intraperitoneal glucose and insulin tolerance tests, western blotting, and quantitative real-time PCR. RESULTS: In vivo studies showed that JLD ameliorated HFD-induced liver injury, significantly decreased body weight and enhanced insulin sensitivity and improved glucose tolerance. Furthermore, JLD suppressed both the mRNA expression of caspase-1 (1.58 vs. 2.90), IL-1ß (0.93 vs. 3.44) and IL-18 (1.34 vs. 1.60) and protein expression of NLRP3 (2.04 vs. 5.71), pro-caspase-1 (2.68 vs. 4.92) and IL-1ß (1.61 vs. 2.60). In vitro, JLD inhibited the formation of lipid droplets induced by 2 mM FFA (IC50 = 2.727 mM), reduced the protein expression of NLRP3 (0.74 vs. 2.27), caspase-1 (0.57 vs. 2.68), p20 (1.67 vs. 3.33), and IL-1ß (1.44 vs. 2.41), and lowered the ratio of p-IKB-α/IKB-α (0.47 vs. 2.19). CONCLUSION: JLD has a protective effect against NAFLD, which may be related to its anti-pyroptosis, suggesting that JLD has the potential as a novel agent in the treatment of NAFLD.

Three-dimensional analysis of lip soft tissue changes and related jaw changes in patients with skeletal class III malocclusion and facial asymmetry.

OBJECTIVE: To investigate three-dimensional soft tissue changes of lips and related jaw changes in patients with skeletal class III malocclusion and facial asymmetry using cone-beam computerized tomography (CBCT). METHOD: This study included 46 CBCT scans of patients with aforementioned character before (T1) and 6-12 months after orthognathic surgery (T2). Subjects were divided into 2 groups according to two types of orthognathic surgery namely, the one-jaw surgery group who underwent bilateral sagittal splint ramus osteotomy (BSSRO) and the two-jaw surgery group who underwent Le Fort I osteotomy and BSSRO. Mimics 19.0 software are used for model reconstruction, landmark location and three-dimensional cephalometric analysis. Descriptive statistics and correlation analyses are used to investigate jaw hard tissue and lip soft tissue changes. RESULTS: In one-jaw group, the mandible shows changes in contour and position (p < 0.05), and the surgery causes changes of lip structure on the deviated side. While in two-jaw group, jaws only show changes in spatial position, and surgery changes contour of bilateral lips and nasolabial angle (p < 0.05). At the same time, lip symmetry increases significantly in both groups postoperatively. CONCLUSIONS: Orthognathic surgery can improve lip aesthetics in patients with skeletal class III malocclusion and facial asymmetry. However, changes induced by two surgical approaches are different. Surgeons should have a clear acquaintance with this difference to deal with different situations.

DNA methylation at CpG island shore and RXRα regulate NR2F2 in heart tissues of tetralogy of Fallot patients.

The nuclear receptor subfamily 2 group F member 2 (NR2F2) gene encodes a ligand-inducible transcription factor involved in angiogenesis and heart development. This study aimed to elucidate the molecular mechanism of epigenetic regulation of NR2F2 in tetralogy of Fallot (TOF) development. In the present study, immunohistochemical staining showed that NR2F2 protein expression was significantly higher in the right ventricular outflow tract (RVOT) tissues of TOF cases compared with controls. The methylation status of the CpG island shore (CGIS) of the NR2F2 gene was decreased in TOF cases, and the CpG site 3 in the CGIS region of NR2F2 promoter was a differential methylation site. Furthermore, the methylation level of the CpG site 3 and the NR2F2 protein expression were significantly negatively correlated in TOF patients. In vitro functional analysis revealed that RXRα could upregulate the NR2F2 gene by directly binding to the CGIS in the NR2F2 promoter, while hypomethylation of the NR2F2 promoter via treatment with 5-azacytidine influenced the affinity of RXRα to its binding sites, as shown by ChIP-qPCR. These findings suggest that promoter hypomethylation activates NR2F2 by enhancing RXRα binding to NR2F2 CGIS in the development of TOF.

Three-dimensional evaluation of skeletal and dental changes in patients with skeletal class III malocclusion and facial asymmetry after surgical-orthodontic treatment.

OBJECTIVE: To evaluate skeletal and dental changes in patients with skeletal Class III malocclusion and facial asymmetry after surgical-orthodontic treatment using cone-beam computerized tomography (CBCT). METHODS: This study included forty adult patients diagnosed with skeletal Class III malocclusion and asymmetry who underwent either isolated mandibular surgery or bimaxillary surgery. CBCT scans were taken before treatment (T0), at the completion of presurgical orthodontic treatment (T1) and after treatment (T2). Mimics 17.0 and 3-Matics 7.0 were used to measure skeletal and dental parameters. Skeletal and dental changes within each group from pretreatment to posttreatment were assessed, and Pearson correlation analysis was used to analyze the correlations among skeletal changes. RESULTS: The three-dimensional changes in condylar position were insignificant after surgical-orthodontic treatment in either group (P > 0.05). However, in the one-jaw surgery group, there were significant backward rotations of the condyle and ramus on the nondeviated side (P < 0.05), and the condyle on the deviated side rotated inward and forward significantly in the two-jaw surgery group (P < 0.05) at T2. There were no significant differences in the changes in the total alveolar bone thickness of bilateral first molars during dental decompensation (P > 0.05). The ratio between the buccal and the total bone thickness around the maxillary first molar on the deviated side decreased significantly at T1, as did those around the mandibular first molar on the nondeviated side (P < 0.05). CONCLUSIONS: Condylar angulations were less stable after treatment (7 to 9 months after surgery) in both the one-jaw and the two-jaw surgery groups, while condylar displacements were insignificant. In addition, orthodontists should keep a watchful eye to the relative position of the root in the alveolar bone during tooth decompensation.

Performance Evaluation of a Newly Developed Chemiluminescent Assay Kit for Detection of Neuron-Specific Eno.

BACKGROUND: To evaluate the performance of a chemiluminescence detection reagent for Neuron-specific enolase (NSE). METHODS: Based on the "Guiding principles on performance analysis of diagnostic, reagents in vitro" and the Clinical and Laboratory Standards Institute (CLSI) Guidelines, performance of the CLIA NSE kit was evaluated, including the detection limit, linear range, reportable range, accuracy, precision, cross reactivity, interference factors, Hook effect, and method comparison. RESULTS: The detection limit of the reagent was 0.05 ng/mL. The linear range of the reagent was 0.05 ng/mL - 400 ng/mL. The reagent can be reported as 0.05 ng/mL - 2,500 ng/mL. The recovery rate ranged from 94.95% to 105.12%. The CV of the reagent of the intra-assay was 3.8% - 5.7% and inter-batch was 3.6%, which meets the requirements. The common interference factors such as the blood fat, jaundice, and rheumatoid factor did not affect the quantitative accuracy of the reagent, but hemolysis resulted in higher readings. Cross-reactions were not observed when incubating with major interfering tumor markers; therefore, the kit was highly specific for NSE. The HOOK effect was not observed when the NSE content reached 20,000 ng/mL in samples. The coincidence rate of the reagent and Roche's products reached 94.81% and the correlation r reached 0.968. CONCLUSIONS: The performance of the NSE CLIA reagent was acceptable in all evaluated parameters, meeting requirements for clinical application.

Transcriptomic responses involved in enhanced production of hypocrellin A by addition of Triton X-100 in submerged cultures of Shiraia bambusicola.

The addition of surfactant is a useful strategy to enhance the product yield in submerged fermentation process. In this study, we sought to explore the mechanism for the elicitation of Triton X-100 on production of hypocrellin A (HA) in cultures of Shiraia bambusicola through transcriptomic analysis. Triton X-100 at 2.5% (w/v) not only induced HA biosynthesis in mycelia, but also stimulated the release of HA into the medium. We found 23 of 2463 transcripts, possible candidate genes for HA biosynthesis under Triton X-100 induction. Gene ontology (GO) analysis showed Triton X-100 treatment changed expression of genes involved in transmembrane transport and oxidation-reduction process, indicating that enhanced HA production was mainly due to both elicited biosynthesis in mycelium and the increased membrane permeability for HA release. These data provided new insights into elicitation of surfactants in submerged cultures of fungi.

[Applications and prospects of on-line near infrared spectroscopy technology in manufacturing of Chinese materia medica].

The quality of Chinese materia medica (CMM) is affected by every process in CMM manufacturing. According to multi-unit complex features in the production of CMM, on-line near infrared spectroscopy (NIR) is used as an evaluating technology with its rapid, non-destructive and non-pollution etc. advantages. With the research in institutions, the on-line NIR applied in process analysis and control of CMM was described systematically, and the on-line NIR platform building was used as an example to clarify the feasibility of on-line NIR technology in CMM manufacturing process. Then, from the point of application by pharmaceutical companies, the current on-line NIR research on CMM and its production in pharmaceutical companies was relatively comprehensively summarized. Meanwhile, the types of CMM productions were classified in accordance with two formulations (liquid and solid dosage formulations). The different production processes (extraction, concentration and alcohol precipitation, etc. ) were used as liquid formulation diacritical points; the different types (tablets, capsules and plasters, etc.) were used as solid dosage formulation diacritical points, and the reliability of on-line NIR used in the whole process in CMM production was proved in according to the summary of literatures in recent 10 years, which could support the modernization of CMM production.

Nanocarrier-Assisted Delivery of Berberine Promotes Diabetic Alveolar Bone Regeneration by Scavenging ROS and Improving Mitochondrial Dysfunction.

Purpose: Oxidative stress and mitochondrial dysfunction are potential contributors to the compromised tissue regeneration capacity of alveolar bone in diabetic patients. Berberine, an active plant alkaloid, exhibits multiple pharmacological effects including antioxidation, blood glucose- and blood lipid-lowering properties. However, it remains uncertain whether berberine can improve impaired osteogenesis in type 2 diabetes mellitus (T2DM), and its poor solubility and oral bioavailability also constrain its applications in bone regeneration. Thus, our study aimed to probe the effects of berberine on bone marrow stem cells (BMSCs) in a diabetic microenvironment, with a greater emphasis on developing a suitable nano-delivery system for berberine and assessing its capability to repair diabetic alveolar bone defects. Methods: Firstly, BMSCs were exposed to berberine within a high glucose and palmitate (HG+PA) environment. Reactive oxygen species levels, mitochondrial membrane potential, ATP generation, cell apoptosis, and osteogenic potential were subsequently assessed. Next, we explored the regulatory mechanism of autophagy flux in the positive effects of berberine. Furthermore, a nanocarrier based on emulsion electrospinning for sustained local delivery of berberine (Ber@SF/PCL) was established. We assessed its capacity to enhance bone healing in the alveolar bone defect of T2DM rats through micro-computed tomography and histology analysis. Results: Berberine treatment could inhibit reactive oxygen species overproduction, mitochondrial dysfunction, apoptosis, and improve osteogenesis differentiation by restoring autophagy flux under HG+PA conditions. Notably, Ber@SF/PCL electrospun nanofibrous membrane with excellent physicochemical properties and good biological safety had the potential to promote alveolar bone remodeling in T2DM rats. Conclusion: Our study shed new lights into the protective role of berberine on BMSCs under T2DM microenvironment. Furthermore, berberine-loaded composite electrospun membrane may serve as a promising approach for regenerating alveolar bone in diabetic patients.

The cytoskeleton dynamics-dependent LINC complex in periodontal ligament stem cells transmits mechanical stress to the nuclear envelope and promotes YAP nuclear translocation.

BACKGROUND: Periodontal ligament stem cells (PDLSCs) are important seed cells in tissue engineering and clinical applications. They are the priority receptor cells for sensing various mechanical stresses. Yes-associated protein (YAP) is a recognized mechanically sensitive transcription factor. However, the role of YAP in regulating the fate of PDLSCs under tension stress (TS) and its underlying mechanism is still unclear. METHODS: The effects of TS on the morphology and fate of PDLSCs were investigated using fluorescence staining, transmission electron microscopy, flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). Then qRT-PCR, western blotting, immunofluorescence staining and gene knockdown experiments were performed to investigate the expression and distribution of YAP and its correlation with PDLSCs proliferation. The effects of cytoskeleton dynamics on YAP nuclear translocation were subsequently explored by adding cytoskeleton inhibitors. The effect of cytoskeleton dynamics on the expression of the LINC complex was proved through qRT-PCR and western blotting. After destroying the LINC complex by adenovirus, the effects of the LINC complex on YAP nuclear translocation and PDLSCs proliferation were investigated. Mitochondria-related detections were then performed to explore the role of mitochondria in YAP nuclear translocation. Finally, the in vitro results were verified by constructing orthodontic tooth movement models in Sprague-Dawley rats. RESULTS: TS enhanced the polymerization and stretching of F-actin, which upregulated the expression of the LINC complex. This further strengthened the pull on the nuclear envelope, enlarged the nuclear pore, and facilitated YAP's nuclear entry, thus enhancing the expression of proliferation-related genes. In this process, mitochondria were transported to the periphery of the nucleus along the reconstructed microtubules. They generated ATP to aid YAP's nuclear translocation and drove F-actin polymerization to a certain degree. When the LINC complex was destroyed, the nuclear translocation of YAP was inhibited, which limited PDLSCs proliferation, impeded periodontal tissue remodeling, and hindered tooth movement. CONCLUSIONS: Our study confirmed that appropriate TS could promote PDLSCs proliferation and periodontal tissue remodeling through the mechanically driven F-actin/LINC complex/YAP axis, which could provide theoretical guidance for seed cell expansion and for promoting healthy and effective tooth movement in clinical practice.

The safety and feasibility assessment of overlap esophagojejunostomy with self-pulling and latter transection technique in totally laparoscopic total gastrectomy.

BACKGROUND: This study presented an innovative technique in totally laparoscopic total gastrectomy (TLTG) for overlap esophagojejunostomy (E-J), termed self-pulling and latter transection (SPLT) (overlap SPLT). It evaluated the effectiveness and short-term outcomes of this novel method through a comparative analysis with the established functional end-to-end (FETE) E-J incorporating SPLT. METHODS: From September 2018 to September 2023, this study enrolled 68 patients with gastric cancer who underwent TLTG with overlap SPLT anastomosis and 120 patients who underwent TLTG with FETE SPLT anastomosis. Clinicopathologic characteristics and surgical and postoperative outcomes data for overlap SPLT cases were gathered and retrospectively compared with those from FETE SPLT TLTG to evaluate the effectiveness and clinical safety. RESULTS: The duration of anastomosis for overlap SPLT was 25.3 ± 7.4 minutes, significantly longer than that for the FETE SPLT (18.1 ± 4.0 minutes, P = .031). Perioperatively, 1 anastomosis-related complication occurred in each group, but this did not constitute a statistically significant difference (P = .682). No statistically significant differences were found between the 2 groups in terms of operative time, postoperative hospital stay, operative cost, surgical margins, or number of lymph nodes removed. Postoperative morbidity rates were similar between the groups (4.4% vs 5.8%, P = .676). CONCLUSION: The overlap SPLT technique is regarded as a safe and feasible method for anastomosis. There were no apparent differences in complications between overlap SPLT and FETE SPLT, but overlap SPLT costed 1 additional stapler cartridge and required a longer duration.

[Exposure characteristics and health risk assessment of 97 typical chemical pollutants in human serum].

Rapid industrial and agricultural developments in China have led to the wide use and discharge of chemical products and pesticides, resulting in extensive residues in environmental media. These residues can enter the human body through various pathways, leading to high exposure risks and health hazards. Because the human body is exposed to a variety of chemical pollutants, accurately quantifying the exposure levels of these pollutants in the human body and evaluating their health risks are of great importance. In this study, the serum concentrations of 97 typical chemical pollutants of 60 adults in central China were simultaneously determined using solid-phase extraction coupled with gas chromatography-tandem mass spectrometry (SPE-GC-MS/MS). In this method, 200 µL of a serum sample was mixed with 10 µL of an isotope-labeled internal standard solution. The sample was vortexed and refrigerated overnight at 4 ℃. Each sample was then deproteinized by the addition of 200 µL of 15% formic acid aqueous solution and vortexed. The serum sample was loaded into a preconditioned Oasis® PRiME HLB SPE cartridge and rinsed with 3 mL of methanol-water (6∶1, v/v). The SPE cartridge was subsequently vacuumed. The analytes were eluted with 3 mL of dichloromethane followed by 3 mL of n-hexane. The eluent was concentrated to near dryness under a gentle nitrogen stream and reconstituted with 100 µL of acetone. The samples were determined by GC-MS/MS and separated on a DB-5MS capillary column (30 m×0.25 mm×0.25 µm) with temperature programming. The column temperature was maintained at 70 ℃ for 2 min, increased at a rate of 25 ℃/min to 150 ℃, increased at a rate of 3 ℃/min to 200 ℃, and then held for 2 min. Finally, the column temperature was increased at a rate of 8 ℃/min to 300 ℃ and maintained at this temperature for 8 min. The samples were detected in multiple-reaction monitoring (MRM) mode and quantitatively analyzed using the internal standard method. Multiple linear regression models were used to analyze the effects of demographic characteristics, lifestyle habits, and diet on the concentrations of the chemical pollutants in the serum samples, and known biomonitoring equivalents (BEs) and human biomonitoring (HBM) values were combined to compute hazard quotients (HQs) and hazard indices (HIs) and evaluate the health risks of single and cumulative exposures to the chemical pollutants. The results showed that the main pollutants detected in human serum were organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The detection rates of eight pollutants, including hexachlorobenzene (HCB) (100%), pentachlorophenol (PCP) (100%), p,p'-dichlorodiphenylene (p,p'-DDE) (100%), PCB-138 (100%), PCB-153 (98.3%), ß-hexachlorocyclohexane (ß-HCH) (91.7%), fluorene (Flu) (85.0%), and anthracene (Ant) (75.0%), were greater than 70%. The serum levels of ß-HCH were higher in females than in males, and age was positively correlated with exposure to p,p'-DDE, PCB-138, PCB-153, and ß-HCH. Increased exposure levels to p,p'-DDE and ß-HCH may be associated with a high frequency of meat intake, whereas increased exposure level to PCP may be associated with a high frequency of vegetable intake. The serum HQ of PCP was greater than 1 in 6.7% of the samples, and no risk was observed for HCB and p,p'-DDE exposure in the study population. Approximately 28.3% of the study subjects had HI values greater than 1. Overall, the general adult population in this region is widely exposed to a wide range of chemical pollutants, and gender, age, and diet are likely to be the main factors influencing the concentration of chemical pollutants. The health risk of single and compound exposures to chemical pollutants should not be ignored.

Clinical characteristics, treatment and efficacy of calcaneal osteomyelitis: A systematic review with synthesis analysis 1118 reported cases.

BACKGROUND: Calcaneal osteomyelitis (CO) still poses great challenges to orthopaedic surgeons due to unique anatomic and functional features of the calcaneus. This study summarized the current data regarding clinical characteristics, treatment and efficacy of CO, based on an analysis of literature-reported cases. MATERIALS AND METHODS: We searched the PubMed, Embase, and Cochrane Library databases to find English and Chinese studies reporting on CO patients between 2000 and 2021, with available data for synthesis analysis. The quality of the included studies was evaluated by the National Institutes of Health (NIH) assessment scale. Effective data were extracted and pooled for analysis. RESULTS: Altogether 198 studies involving 1118 patients were included, with a male-to-female ratio of 2.3 (724 males and 310 females). The median age at CO diagnosis was 46 years, with a median symptom duration of 3 months. Injury-related infections (524 cases) and diabetic foot infections (336 cases) were the two most common causes, with ulcer (468 cases) and wound sinus or exudation (209 cases) being the predominant symptoms. The overall positive culture rate was 80.2%, with polymicrobial infections accounting for 18.1%. Staphylococcus aureus was the most frequently detected pathogen (42.7%), with fungal-related infections isolated in 17 cases. Although most patients received surgical interventions (96.9%), the recurrence rate was 20.1%. The incidence of infection relapse following partial calcanectomy, total calcanectomy, debridement with implantation of local antibiotics, and debridement with or without flap or skin coverage were 31.7%, 45.0%, 16.8%, and 15.1%, respectively. The overall incidence of limb amputation was 12.4%, with all-cause and CO-related mortalities of 2.8% and 0.2%, separately. CONCLUSIONS: CO shared similar characteristics with extremity chronic osteomyelitis, primarily affecting young males, with trauma and diabetic foot as the leading causes and Staphylococcus aureus as the most frequently detected pathogen. Despite surgery being the primary treatment modality, clinical outcomes remained unsatisfactory, marked by high rates of infection recurrence and limb amputation.

Effective screening strategy using ensembled pharmacophore models combined with cascade docking: application to p53-MDM2 interaction inhibitors.

Protein-protein interactions (PPIs) play a crucial role in cellular function and form the backbone of almost all biochemical processes. In recent years, protein-protein interaction inhibitors (PPIIs) have represented a treasure trove of potential new drug targets. Unfortunately, there are few successful drugs of PPIIs on the market. Structure-based pharmacophore (SBP) combined with docking has been demonstrated as a useful Virtual Screening (VS) strategy in drug development projects. However, the combination of target complexity and poor binding affinity prediction has thwarted the application of this strategy in the discovery of PPIIs. Here we report an effective VS strategy on p53-MDM2 PPI. First, we built a SBP model based on p53-MDM2 complex cocrystal structures. The model was then simplified by using a Receptor-Ligand complex-based pharmacophore model considering the critical binding features between MDM2 and its small molecular inhibitors. Cascade docking was subsequently applied to improve the hit rate. Based on this strategy, we performed VS on NCI and SPECS databases and successfully discovered 6 novel compounds from 15 hits with the best, compound 1 (NSC 5359), K(i) = 180 ± 50 nM. These compounds can serve as lead compounds for further optimization.

[Near infrared distance sensing method for Chang'e-3 alpha particle X-ray spectrometer].

Alpha particle X-ray spectrometer (APXS) is one of the payloads of Chang'E-3 lunar rover, the scientific objective of which is in-situ observation and off-line analysis of lunar regolith and rock. Distance measurement is one of the important functions for APXS to perform effective detection on the moon. The present paper will first give a brief introduction to APXS, and then analyze the specific requirements and constraints to realize distance measurement, at last present a new near infrared distance sensing algorithm by using the inflection point of response curve. The theoretical analysis and the experiment results verify the feasibility of this algorithm. Although the theoretical analysis shows that this method is not sensitive to the operating temperature and reflectance of the lunar surface, the solar infrared radiant intensity may make photosensor saturation. The solutions are reducing the gain of device and avoiding direct exposure to sun light.

A validated LC-MS/MS method for the determination of vinflunine in plasma and its application to pharmacokinetic studies.

A rapid, simple and sensitive LC-MS/MS method for the quantification of vinflunine in plasma was developed and validated. The analysis involved a simple liquid-liquid extraction. After making alkaline with NaOH, plasma was extracted with methyl tert-butyl ether and the organic extract was then evaporated and the residue was reconstituted in mobile phase. The reconstituted solution was injected into an HPLC system and was subjected to reverse-phase HPLC on a 5 µm ODS-3 column at a flow-rate of 0.2 mL/min. The mobile phase consisted of ammonium acetate (0.02 mol/L, pH = 3.0) and acetonitrile (20:80). Vinflunine was detected in the single ion monitoring mode using target ions at m/z 817.4/160.1/142.3 for vinflunine and m/z 447.2/128.3/112.1 for gefitinib (internal standard). Standard curves were linear over the concentration range of 5-1000 ng/mL. The mean predicted concentrations of the quality control samples deviated by less than 2% from the corresponding nominal values; the intra-assay and inter-assay precisions of the assay were within 7% relative standard deviation. The extraction recovery of vinflunine was more than 80%. The validated assay was applied to a pharmacokinetic study of vinflunine in plasma following the administration of a single vinflunine injection (2 mg/kg).