Drinking brick tea containing high fluoride increases the prevalence of osteoarthritis in Tibetan, China.

The prevalence of osteoarthritis (OA) in Tibetans is higher than that in Han, while Tibetans have a habit of drinking brick tea with high fluoride. A cross-sectional study was conducted to explore the association between fluoride exposure in drinking brick tea and OA. All subjects were divided into four groups by the quartiles (Q) of tea fluoride (TF) and urine fluoride (UF). ROC was plotted and OR were obtained using logistic regression model. The prevalence of OA in the Q3 and Q4 group of TF were 2.2 and 2.7 times higher than in the Q1 group, and the prevalence of OA in the Q2, Q3 and Q4 group of UF were 3.2, 3.5, and 4.1 times higher than in the Q1 group. ROC analysis showed the cutoff values were 4.523 mg/day (TF) and 1.666 mg/L (UF). In conclusion, excessive fluoride in drinking brick tea could be a risk factor for developing OA.

The 2023 Orthopedic Research Society's international consensus meeting on musculoskeletal infection: Summary from the in vitro section.

Antimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates. Here, we report recommendations and rationale from the reviews and the results of the internet vote. Only two questions received a ≥90% consensus vote, emphasizing the disparate approaches and lack of established consensus for in vitro modeling and interpretation of results. Comments on knowledge gaps and the need for further research on these critical MSKI questions are included.

Dichlorodiphenyltrichloroethane for Malaria and Agricultural Uses and Its Impacts on Human Health.

Pesticides are widely used in agriculture and disease control, and dichlorodiphenyltrichloroethane (DDT) is one of the most used pesticides in human history. Besides its significant contributions in pest control in agriculture, DDT was credited as having saved millions of human lives for controlling malaria and other deadly insect-transmitted diseases. Even today, the use of DDT in some countries for malaria control cannot be replaced without endangering people who live there. The recent COVID-19 pandemic has changed our lives and reminded us of the challenges in dealing with infectious diseases, especially deadly ones including malaria. However, DDT and its metabolites are stable, persist long, are found in almost every corner of the world, and their persistent effects on humans, animals, and the environment must be seriously considered. This review will focus on the history of DDT use for agriculture and malaria control, the pathways for the spread of DDT, benefits and risks of DDT use, DDT exposure to animals, humans, and the environment, and the associated human health risks. These knowledge and findings of DDT will benefit the selection and management of pesticides worldwide.

Advances in Antimicrobial Peptide Discovery via Machine Learning and Delivery via Nanotechnology.

Antimicrobial peptides (AMPs) have been investigated for their potential use as an alternative to antibiotics due to the increased demand for new antimicrobial agents. AMPs, widely found in nature and obtained from microorganisms, have a broad range of antimicrobial protection, allowing them to be applied in the treatment of infections caused by various pathogenic microorganisms. Since these peptides are primarily cationic, they prefer anionic bacterial membranes due to electrostatic interactions. However, the applications of AMPs are currently limited owing to their hemolytic activity, poor bioavailability, degradation from proteolytic enzymes, and high-cost production. To overcome these limitations, nanotechnology has been used to improve AMP bioavailability, permeation across barriers, and/or protection against degradation. In addition, machine learning has been investigated due to its time-saving and cost-effective algorithms to predict AMPs. There are numerous databases available to train machine learning models. In this review, we focus on nanotechnology approaches for AMP delivery and advances in AMP design via machine learning. The AMP sources, classification, structures, antimicrobial mechanisms, their role in diseases, peptide engineering technologies, currently available databases, and machine learning techniques used to predict AMPs with minimal toxicity are discussed in detail.

Chemical Synthesis of Innovative Silver Nanohybrids with Synergistically Improved Antimicrobial Properties.

Background: The wide use of antibiotics has created challenges related to antibiotic-resistant bacteria, which have been increasingly found in recent decades. Antibiotic resistance has led to limited choices of antibiotics. Multiple old antimicrobial agents have high antimicrobial properties toward bacteria, but they unfortunately also possess high toxicity toward humans. For instance, silver (Ag) compounds were frequently used to treat tetanus and rheumatism in the 19th century and to treat colds and gonorrhea in the early 20th century. However, the high toxicity of Ag has limited its clinical use. Purpose: We aimed to reformulate Ag to reduce its toxicity toward human cells like osteoblasts and to optimize its antimicrobial properties. Results: Ag, an old antimicrobial agent, was reformulated by hybriding nanomaterials of different dimensions, and silver nanoparticles (AgNPs) of controllable sizes (95-200 nm) and varying shapes (cube, snowflake, and sphere) were synthesized on carbon nanotubes (CNTs). The obtained AgNP-CNT nanohybrids presented significantly higher killing efficacy against Staphylococcus aureus (S. aureus) compared to AgNPs at the same molar concentration and showed synergism in killing S. aureus at 0.2 and 0.4 mM. AgNPs presented significant osteoblast toxicity; in contrast, AgNP-CNT nanohybrids demonstrated significantly enhanced osteoblast viability at 0.04-0.8 mM. The killing of S. aureus by AgNP-CNT nanohybrids was fast, occurring within 15 min. Conclusion: Ag was successfully reformulated and Ag nanohybrids with various AgNP shapes on CNTs were synthesized. The nanohybrids presented significantly enhanced antimicrobial properties and significantly higher osteoblast cell viability compared to AgNPs, showing promise as an innovative antimicrobial nanomaterial for a broad range of biomedical applications.

Fluoride induced metabolic disorder of endothelial cells.

Endemic fluorosis is a global public health problem. Cardiovascular diseases caused by fluoride are closely related to endothelial cell injury. Metabolism disorder of endothelial cells (ECs) are recognized as the key factor of endothelial dysfunction which has been a hot topic in recent years. However, the toxic effect of fluoride on vascular endothelium has not been elucidated. The aim of this study was to explore the alteration of endothelial cell metabolites in Human Umbilical Vein Endothelial Cells (HUVECs) exposed to NaF using LC-MS/MS technique. The screening conditions were Variable Importance for the Projection (VIP) > 1 and P < 0.05. It was found that the expression of the metabolites Lumichrome and S-Methyl-5'-thioadenosine was upregulated and of the other metabolites, such as Creatine, L-Glutamate, Stearic acid was downregulated. Differential metabolites were found to be primarily related to FoxO、PI3K/Akt and apoptosis signaling pathways by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. From the perspective of metabolism, this study explored the possible mechanism of fluoride induced endothelial cell injury which providing theories and clues for subsequent studies.

Environment and chronic disease in rural areas of Heilongjiang, China (ECDRAHC).

PURPOSE: Environmental factors such as long-term exposure to cold can increase the risk of chronic diseases. However, few studies have focused on the impact of environmental factors and lifestyle changes on chronic diseases. To fully explore the association between exposure to environmental factors and the prevalent risk of various chronic diseases, we conducted a large cohort study (Environment and Chronic Disease in Rural Areas of Heilongjiang, China (ECDRAHC)). The ECDRAHC collected detailed questionnaire data covering 10 sections, physical measurements and blood and urine samples. In this study, we describe the design and implementation of the cohort study and present the findings for the first 10 000 participants. PARTICIPANTS: The ECDRAHC study was carried out in rural areas where the annual average temperature is 2.9°C, and aimed to recruit 40 000 participants who are long-term residents aged 35-74 years. The participants will be followed up every 5 years. Currently, ECDRAHC has reached 26.7% (n=10 694) of the targeted population. FINDINGS TO DATE: A total of 10 694 adults aged 35-74 years were recruited, including 61.7% women. The prevalence of current smokers was 46.8% in men and 35.4% in women. The mean blood pressure was 140.2/89.9 mm Hg and 135.7/85.0 mm Hg in men and women, respectively. The mean body mass index was 24.74 kg/m2 in men and 24.65 kg/m2 in women, with >7.3% being obese (>30 kg/m2). The main non-communicable diseases found in phase 1 were hypertension, diabetes, hypertriglyceridaemia and metabolic syndrome, with a higher prevalence of 51.0%, 21.6%, 46.8% and 42.6%, respectively. FUTURE PLANS: We plan to complete the follow-up for the first phase of the ECDRAHC in 2024. The second and third phase of the cohort will be carried out steadily, as planned. This cohort will be used to investigate the relationship between environmental factors, lifestyle, and genetic and common chronic diseases.

Operator-as-a-Consumer: A Novel Energy Storage Sharing Approach Under Demand Charge.

Energy storage systems (ESSs)-based demand response (DR) is an appealing way to save electricity bills for consumers under demand charge and time-of-use (TOU) price. In order to counteract the high investment cost of ESS, a novel operator-enabled ESS sharing scheme, namely, the "operator-as-a-consumer (OaaC)," is proposed and investigated in this article. In this scheme, the users and the operator form a Stackelberg game. The users send ESS orders to the operator and apply their own ESS dispatching strategies for their own purposes. Meanwhile, the operator maximizes its profit through optimal ESS sizing and scheduling, as well as pricing for the users' ESS orders. The feasibility and economic performance of OaaC are further analyzed by solving a bilevel joint optimization problem of ESS pricing, sizing, and scheduling. To make the analysis tractable, the bilevel model is first transformed into its single-level mathematical program with equilibrium constraints (MPEC) formulation and is then linearized into a mixed-integer linear programming (MILP) problem using multiple linearization methods. Case studies with actual data are utilized to demonstrate the profitability for the operator and simultaneously the ability of bill saving for the users under the proposed OaaC scheme.

Evaluation of Risk Factors for Chronic Obstructive Pulmonary Disease in the Middle-Aged and Elderly Rural Population of Northeast China Using Logistic Regression and Principal Component Analysis.

Purpose: To investigate the environmental, immune, and inflammatory factors associated with chronic obstructive pulmonary disease (COPD) in middle-aged and older Chinese individuals. Patients and Methods: A community-based case-control study was conducted among 471 patients with COPD and 485 controls. The information on COPD of the participants was collected through face-to-face interviews, and serum samples were measured at the laboratory. The main risk factors for COPD were analyzed using principal component analysis (PCA) and logistic regression. Results: Nine hundred and fifty-six respondents were included in the analysis. The results of the PCA-logistic regression analysis showed significant differences in the environmental factors, medical history, and serum C-reactive protein (CRP) levels between patients and controls. COPD was markedly more usual in those with smoking index >200 (OR, 1.42; 95% CI, 1.28-1.57); exposure to outdoor straw burning (OR, 1.64; 95% CI, 1.47-1.83); use of coal, wood, and straw indoors (OR, 2.31; 95% CI, 1.92-2.78); history of respiratory disease and coronary heart disease (OR, 3.58; 95% CI, 3.12-4.10), congestive heart failure (OR, 1.23; 95% CI, 1.09-1.38), and cerebrovascular disease (OR, 1.15; 95% CI,1.02-1.31); and higher serum level of CRP (OR, 1.20; 95% CI, 1.11-1.30). Compared to the logistic regression analysis, PCA logistic regression analysis identified more important risk factors for COPD. Conclusion: PCA-logistic regression analysis was first utilized to explore the influencing factors among rural residents in Northeast China Environmental aged 40 years and above, it was found that environmental factors, medical history, and serum CRP levels mainly affected the prevalence of COPD.

Nature-Derived Okra Gel as Strong Hemostatic Bioadhesive in Human Blood, Liver, and Heart Trauma of Rabbits and Dogs.

Bioadhesive performance can be compromised due to bleeding. Bleeding increases mortality. Adhesives with hemostatic function are of great significance. A sustainable and robust hemostatic bioadhesive from okra is reported. The adhesive strength reaches around three and six-fold higher than commercial fibrin on pigskin and glass, respectively. The okra gel presents high-pressure resistance and great underwater adhesive strength. In human blood experiments, the okra gel can activate platelets, enhance the adhesion of activated platelets, and release coagulation factors XI and XII. By forming a fast gel layer and closely adhering to the wound, it can quickly stop bleeding in the liver and heart of rabbits and dogs. Meanwhile, okra gel can cause platelet activation at the wound site and further strengthen its hemostatic performance. It is biocompatible, biodegradable, and can promote wound healing and shows potential as a sustainable bioadhesive, especially in the scenario of significant hemorrhage.

Gelation of highly entangled hydrophobic macromolecular fluid for ultrastrong underwater in situ fast tissue adhesion.

Although strong underwater bioadhesion is important for many biomedical applications, designing adhesives to perform in the presence of body fluids proves to be a challenge. To address this, we propose an underwater and in situ applicable hydrophobic adhesive (UIHA) composed of polydimethylsiloxane, entangled macromolecular silicone fluid, and a reactive silane. The hydrophobic fluid displaced the boundary water, formed an in situ gel, bonded to tissues, and achieved exceptional underwater adhesion strength. Its underwater lap shear adhesion on porcine skin was significantly higher than that of cyanoacrylate and fibrin glues, demonstrating excellent water resistance. The burst pressure of UIHA on porcine skin was 10 times higher than that of fibrin glue. The cytocompatible UIHA successfully sealed ruptured arteries, skin, and lungs in rats, pigs, rabbits, and dogs. Together, the gelation of highly entangled hydrophobic macromolecular fluid provided a means to prepare underwater bioadhesives with strong bonding to tissues and excellent water resistance.

Layer-by-Layer Cell Encapsulation for Drug Delivery: The History, Technique Basis, and Applications.

The encapsulation of cells with various polyelectrolytes through layer-by-layer (LbL) has become a popular strategy in cellular function engineering. The technique sprang up in 1990s and obtained tremendous advances in multi-functionalized encapsulation of cells in recent years. This review comprehensively summarized the basis and applications in drug delivery by means of LbL cell encapsulation. To begin with, the concept and brief history of LbL and LbL cell encapsulation were introduced. Next, diverse types of materials, including naturally extracted and chemically synthesized, were exhibited, followed by a complicated basis of LbL assembly, such as interactions within multilayers, charge distribution, and films morphology. Furthermore, the review focused on the protective effects against adverse factors, and bioactive payloads incorporation could be realized via LbL cell encapsulation. Additionally, the payload delivery from cell encapsulation system could be adjusted by environment, redox, biological processes, and functional linkers to release payloads in controlled manners. In short, drug delivery via LbL cell encapsulation, which takes advantage of both cell grafts and drug activities, will be of great importance in basic research of cell science and biotherapy for various diseases.

Changes of network structure and water distribution in sludge with the stratified extraction of extracellular polymeric substances.

The water in sludge is trapped within the extracellular polymeric substance (EPS) with gelatinous structure, greatly challenging the sludge deep dewatering. In this paper, the effect of the EPS viscoelasticity and the structural characteristics of sludge flocs on water distribution was revealed to provide a highly efficient approach in research on sludge dewatering. After biological, and physical method conditioning, the change of viscoelasticity and sludge network structure before/after EPS extraction was comprehensively explored, together with the sludge dewaterability and water distribution. The results suggested the proportion of capillary water and adsorption water carried in soluble EPS (S-EPS) was 59.17% and 40.83%, and that in tightly bound EPS (TB-EPS) was 54.77% and 45.23%, respectively. By contrast, the capillary water in loosely bound EPS (LB-EPS) accounted for as high as 99.99%. In comparison with raw sludge, adsorption water proportion in TB-EPS and S-EPS was reduced after lysozyme (LZM) or freezing-thaw conditioning, which was ascribed to reduction of EPS viscosity and the weakness of water adsorption capacity. Additionally, the sludge yield stress (τy) value first reduced and then increased with the extraction of EPS. Meanwhile, the consistency coefficient (k) also decreased from 4.23 Pa·sn to 0.006 Pa·sn and then slightly increased after LZM conditioning. This observation indicated the sludge system became sensitive to shearing, and its network structural strength as well as colloid elasticity first weakened and then slightly strengthened. In addition, after LZM or freezing-thaw conditioning, the sludge particle size significantly increased after TB-EPS extraction, while the sludge particle more easily absorbed water molecules, thereby increasing adsorption water and capillary water within the sludge flocs. This phenomenon also resulted in an increasing trend of capillary suction time (CST) after TB-EPS extraction, indicating the deterioration of sludge filtration performance.

Association between Bone Morphogenetic Protein 2 Gene Polymorphisms and Skeletal Fluorosis of The Brick-tea Type Fluorosis in Tibetans and Kazakhs, China.

To investigate the potential association between BMP2 single nucleotide polymorphisms (SNPs) and brick-tea-type skeletal fluorosis risk in cross-sectional case-control study conducted in Sinkiang and Qinghai, China, a total of 598 individuals, including 308 Tibetans and 290 Kazakhs, were enrolled. Using the standard WS/192-2008 (China), 221 skeletal fluorosis cases were diagnosed, including 123 Tibetans and 98 Kazakhs. Logistic regressions 2 analysis did not find the association between SNPs (Rs235764, Rs235739 and Rs996544) and skeletal fluorosis. Genetic models, linkage disequilibrium (LD) and haplotype analysis were not found to be associated with risk of skeletal fluorosis after adjustment by age and sex (P>0.05).Our data suggested that Rs 235764, Rs 235739 and Rs 996544 were not linked susceptibility for skeletal fluorosis in our cross-sectional case-control study.

Injectable and conductive cardiac patches repair infarcted myocardium in rats and minipigs.

Cardiac patches can help to restore the electrophysiological properties of the heart after myocardial infarction. However, scaffolds for the repair of heart muscle typically require surgical implantation or, if they are injectable, they are not electrically conductive or do not maintain their shape or function. Here, we report the performance, as demonstrated for the repair of infarcted heart muscle in rats and minipigs, of injectable and conductive scaffolds consisting of methacrylated elastin and gelatin, and carbon nanotubes that display shape-memory behaviour, a hierarchical porous structure and a negligible Poisson's ratio. In rats, the implantation of cell-free patches or patches seeded with rat cardiomyocytes onto the myocardium after ligation of the left anterior descending coronary artery led to functional repair after 4 weeks, as indicated by increases in fractional shortening and the ejection fraction, and by a decrease in the infarcted area. We also observed measures of functional recovery in minipigs with infarcted hearts after the delivery of cell-free patches or patches incorporating cardiomyocytes differentiated from human pluripotent stem cells.

Synergy coordination of cellulose-based dialdehyde and carboxyl with Fe3+ recoverable conductive self-healing hydrogel for sensor.

A novel dual ionic network cellulose-based composite conductive self-healing hydrogel was fabricated with high elongation, rapid recoverability, high conductive sensitivity, self-healing ability and good biocompatibility. The hydrogel was constructed by the synergistic complexations of new-fashioned bidentate aldehyde groups on dialdehyde cellulose nanofibers (DACNFs) and carboxyl groups of acrylic acid (AA) with Fe3+. The elongation (~1300%) of the hydrogel containing 1 wt% DACNFs was approximate 13-fold of the pure PAA hydrogel and can recover to original state within 2 min after 80% compression. The self-healing efficiency increased with the addition of DACNFs in the dual ionic network cellulose-based composite conductive self-healing hydrogel. The hydrogel configured for a wearable test and showed high stretching sensitivity with a gauge factor of 13.82 at strain within 1.6%. The gauge factor (GF) decrease with the incremental strain within 20%. GF were 0.696 between 20% and 300% strain, 0.837 within 300% and 500%. Meanwhile, the current had a good linear relationship with the bending angles of hydrogels and pressure on hydrogels, which may provide a great potential in monitor both minor variations and large movements.

Effect of atrazine on accumulation of iron via the iron transport proteins in the midbrain of SD rats.

Atrazine (ATR), a widely used herbicide that belongs to the triazine class, has detrimental effects on several organ systems. It has also been shown that ATR exposure results in dopaminergic neurotoxicity. However, the mechanism of herbicides causing ferroptosis in neurons is less concerned. So, the present study aimed to investigate the effects of long-term oral exposure to ATR on ferroptosis in adult male rats. In this study, we show that there was a dose-dependent increase in the concentration of iron in the midbrain. Simultaneously, the expression of tyrosine hydroxylase (TH) and Synuclein (α-syn) were altered by the ATR. We carried out miRNA profiling brain tissue in order to identify factors that mediate ferroptosis. We also found that the mRNA and protein expression of the transferrin receptor (TFR), divalent metal transporter 1 (DMT1), hephaestin (HEPH), and ferroportin 1 (Fpn1) in the midbrain were affected by ATR. Based on the current results and previously published data, it is clear that exposure of adult male rats to high doses of ATR leads to iron loading in the midbrain. The long-term adverse effects of ATR on the midbrain have a special relevance after exposure.

Programmed Multidrug Delivery Based on Bio-Inspired Capsule-Integrated Nanocoatings for Infected Bone Defect Treatment.

Infection and delayed wound healing are two major serious complications related to traumatic injuries and cause a significant burden to patients and society. Most currently available drug delivery materials typically carry a single drug, lack protection from drug loading, and face challenges in on-demand and precisely controlled drug release. Here, we report a flower (Cirsium arvense)-inspired capsule-integrated multilayer nanofilm (FICIF), synthesized using a layer-by-layer self-assembly, for programmed multiple drug co-delivery for trauma (open fracture as an example) treatments. Our approach allows polypeptide multilayer nanofilms and innovative impregnated capsules to assemble hierarchical reservoirs with specific drug binding sites, shielding protection capability, and ordered packing structures. The resultant FICIF nanocarriers enable sustained and on-demand co-delivery of a unique immune-tuning cytokine (interleukin 12p70) and a growth factor (bone morphogenetic protein 2) in clinical use, resulting in extraordinary anti-infection (3 orders of magnitude improved bacterial killing) and bone regeneration (5 times enhanced bone healing) in treating infected rat femur fractures. The successful synthesis of these biomimetic high-performance delivery nanocoatings is expected to serve as a source of inspiration for the development of biomaterials for various clinical applications.

Cellulose-based thermo-enhanced fluorescence micelles.

Recently, cellulose-based stimuli-responsive nanomaterials have received significant attention because of its natural source and biocompatibility. In this study, cellulose-graft-poly(nisopropylacrylamide)-co-2-methyl-acrylic acid 2-carbazol-9-yl-ethyl ester (cellulose-g-(PNIPAAm&PCz)) block polymers were successfully synthesized by homogeneous atom transfer radical polymerization (ATRP) in LiCl/N,N-dimethylacetamide (DMAc) dissolution system. The block polymers showed different properties due to the different PCz content. The block polymer with low PCz content (cellulose-g-(PNIPAAm&PCz)1) was dispersed in water at 25 °C and self-assembled into micelles at 37 °C. On the other hand, the block polymer with high PCz content (cellulose-g-(PNIPAAm&PCz)2) was dissolved in DMF, THF, DMSO firstly, and dialyzed at 25 °C, 37 °C and 60 °C respectively to obtain the micelles. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) indicated that the distribution range of micelles formed by cellulose-g-(PNIPAAm&PCz)1 was narrower than cellulose-g-(PNIPAAm&PCz)2. And the sizes of the micelles formed by cellulose-g-(PNIPAAm&PCz)2 had little difference under different solvents, but became bigger with the temperature increased. The micelles displayed thermo-enhanced fluorescence due to the thermal-driven chain dehydration of the grafted PNIPAAm brushes, which is contrary to the decrease of the fluorescence of the monomer when the temperature increased. The results provided a potential for the application of cellulose-based stimuli-responsive micelles in the field of drug delivery and fluorescent probes.

Multi-functional flexible 2D carbon nanostructured networks.

Two-dimensional network-structured carbon nanoscale building blocks, going beyond graphene, are of fundamental importance, and creating such structures and developing their applications have broad implications in environment, electronics and energy. Here, we report a facile route, based on electro-spraying/netting, to self-assemble two-dimensional carbon nanostructured networks on a large scale. Manipulation of the dynamic ejection, deformation and assembly of charged droplets by control of Taylor cone instability and micro-electric field, enables the creation of networks with characteristics combining nanoscale diameters of one-dimensional carbon nanotube and lateral infinity of two-dimensional graphene. The macro-sized (meter-level) carbon nanostructured networks show extraordinary nanostructural properties, remarkable flexibility (soft polymeric mechanics having hard inorganic matrix), nanoscale-level conductivity, and outstanding performances in distinctly different areas like filters, separators, absorbents, and wearable electrodes, supercapacitors and cells. This work should make possible the innovative design of high-performance, multi-functional carbon nanomaterials for various applications.