Integrated Experimental and Mathematical Exploration of Modular Tissue Cultures for Developmental Engineering.

Developmental engineering (DE) involves culturing various cells on modular scaffolds (MSs), yielding modular tissues (MTs) assembled into three-dimensional (3D) tissues, mimicking developmental biology. This study employs an integrated approach, merging experimental and mathematical methods to investigate the biological processes in MT cultivation and assembly. Human dermal fibroblasts (HDFs) were cultured on tissue culture plastics, poly(lactic acid) (PLA) discs with regular open structures, or spherical poly(methyl methacrylate) (PMMA) MSs, respectively. Notably, HDFs exhibited flattened spindle shapes when adhered to solid surfaces, and complex 3D structures when migrating into the structured voids of PLA discs or interstitial spaces between aggregated PMMA MSs, showcasing coordinated colonization of porous scaffolds. Empirical investigations led to power law models simulating density-dependent cell growth on solid surfaces or voids. Concurrently, a modified diffusion model was applied to simulate oxygen diffusion within tissues cultured on solid surfaces or porous structures. These mathematical models were subsequently combined to explore the influences of initial cell seeding density, culture duration, and oxygen diffusion on MT cultivation and assembly. The findings underscored the intricate interplay of factors influencing MT design for tissue assembly. The integrated approach provides insights into mechanistic aspects, informing bioprocess design for manufacturing MTs and 3D tissues in DE.

Bioinspired nervous signal transmission system based on two-dimensional laminar nanofluidics: From electronics to ionics.

Mammalian nervous systems, as natural ionic circuitries, stand out in environmental perception and sophisticated information transmission, relying on protein ionic channels and additional necessary structures. Prosperously emerged ionic regulated biomimetic nanochannels exhibit great potentialities in various application scenarios, especially signal transduction. Most reported direct current systems possess deficiencies in informational density and variability, which are superiorities of alternating current (AC) systems and necessities in bioinspired nervous signal transmission. Here, inspired by myelinated saltatory conduction, alternating electrostatic potential controlled nanofluidics are constructed with a noncontact application pattern and MXene nanosheets. Under time-variant external stimuli, ions confined in the interlaminar space obtain the capability of carriers for the AC ionic circuit. The transmitted information is accessible from typical sine to a frequency-modulated binary signal. This work demonstrates the potentiality of the bioinspired nervous signal transmission between electronics and ionic nanofluidics, which might push one step forward to the avenue of AC ionics.

The significance of the best puncture side bone cement/vertebral volume ratio to prevent paravertebral vein leakage of bone cement during vertebroplasty: a retrospective study.

OBJECTIVES: To verify the clinical significance of the best puncture-side bone cement/vertebral volume ratio (PSBCV/VV%) and bone cement leakage in paravertebral veins during vertebroplasty. METHODS: This was a retrospective analysis of a total of 210 patients from September 2021 to December 2022, who were divided into an observation group (110 patients) and a control group (100 patients). In the observation group, patients' preoperative computed tomography (CT) data were imported into Mimics software, and the VV was calculated using the three-dimensional (3D) reconstruction function. Then, based on the best PSBCV/VV% of 13.68% determined in a previous study, the optimal PSBCV to be injected during vertebroplasty was calculated. In the control group, vertebroplasty was performed directly using the conventional method. The incidence of cement leakage into paravertebral veins was observed postoperatively in both groups. RESULTS: There were no statistically significant differences (P > 0.05) in the evaluated indicators between the two groups pre- or postoperatively, including the anterior vertebral margin height, mid-vertebral height, injured vertebral Cobb angle, visual analogue scale (VAS) score, and Oswestry Disability Index (ODI). Intragroup comparisons showed improvements in the anterior vertebral height, mid-vertebral height, injured vertebral Cobb angle, VAS score, and ODI after surgery compared with before surgery (P < 0.05). In the observation group, there were 3 cases of cement leakage into the paravertebral veins, for a leakage rate of 2.7%. In the control group, there were 11 cases of cement leakage into the paravertebral veins, for a leakage rate of 11%. The difference in the leakage rate between the two groups was statistically significant (P = 0.016). CONCLUSION: In vertebroplasty, preoperative VV calculations using Mimics software, combined with calculation of the PSBCV according to the best PSBCV/VV% (13.68%), can effectively prevent leakage of bone cement into paravertebral veins and further prevent serious life-threatening complications such as pulmonary embolism.

First report of cobweb disease in Auricularia cornea caused by Hypomyces mycophilus in Guizhou, China.

Auricularia cornea is a widely cultivated mushroom in China, which has high medicinal values such as hemostaticity, analgesia, antioxidation and anti-tumor (Wu et al., 2019). In 2022, an investigation on edible mushroom diseases in Guizhou Province observed a suspected cobweb disease in an A. cornea growing factory, with up to 30% incidence. The pathogen first produced flocculent hyphae on the surface of the fruiting body of A. cornea, and then developed spider web-like aerial hyphae, covering the entire fruiting bodies. It hinders the normal growth of A. cornea, resulting in deformity and rot of the fruiting bodies. These symptoms seriously affect the quantity and quality of mushroom yields and cause huge economic losses. Three fungal isolates (GUCCX001, GUCCX002 and GUCCX003) were recovered from the diseased mushroom fruiting bodies and purified through single spore isolation. The colonies of three isolates spread rapidly on PDA, reaching 79-82 mm in seven days. The flocculent mycelium was whitish, and its reverse turned from yellowish to amber after 14 days. The branched conidiophores arising from aerial mycelia were septate and each cell contained several denticulate conidiogenous loci. Each denticle contained a single conidium. Conidia were observed at the tip of conidiophore branches and were 0-1-septate, oval or spherical, transparent, 5.2-11.3 × 11.7-18.7 µm (n = 35). Chlamydospores were visible as 3-4 thick-walled cells at the tip of lateral hyphal branches. Three isolates were tentatively identified as H. mycophilus based on their morphological characteristics similar to those described by Rogerson and Samuels (1993). The sequence of internal transcribed spacer (ITS) region (primers ITS5/ITS4) (Rehner and Samuels, 1994) and nuclear ribosomal large subunit (LSU) region (primers LR0R/LR5) (Vilgalys and Heste, 1990) of GUCCX001 (ITS: OP777905; LSU: OQ152071), GUCCX002 (ITS: OP862872; LSU: OQ152072) and GUCCX003 (ITS: OP862873; LSU: OP862873) were 99%-100% similar to H. mycophilus CBS 175.56 (ITS: MH857567; LSU: MH869110). Fifteen healthy fruiting bodies of A. cornea were inoculated by spraying spore suspension (106 conidia/mL) of the three isolates and five healthy fruiting bodies were sprayed with sterile water as control. All inoculated fruiting bodies were kept at 25 ℃. After three days, fruiting bodies of A. cornea treated with the spore suspension exhibited the same symptoms of cobweb as in the factory, while no symptom appeared in the control. Pathogens re-isolated from diseased fruiting bodies were confirmed to be H. mycophilus based on morphological characteristics, which fulfills the Koch's postulate. Zeng et al. (2017) reported H. mycophilus on the fruiting bodies of Auricularia sp. as a new record in Guangdong, China. H. mycophilus caused cobweb disease on A. auricula (Liu et al., 2020), A. cornea var. Li. (Cao et al., 2023) and A. heimuer (Zhang et al., 2023). To our knowledge, this is the first report of cobweb disease in A. cornea caused by H. mycophilus in Guizhou, China. Our findings will provide a basis for correct diagnosis and management of cobweb diseases on A. cornea.

Evaluation of Polymeric Particles for Modular Tissue Cultures in Developmental Engineering.

Developmental engineering (DE) aims to culture mammalian cells on corresponding modular scaffolds (scale: micron to millimeter), then assemble these into functional tissues imitating natural developmental biology processes. This research intended to investigate the influences of polymeric particles on modular tissue cultures. When poly(methyl methacrylate) (PMMA), poly(lactic acid) (PLA) and polystyrene (PS) particles (diameter: 5-100 µm) were fabricated and submerged in culture medium in tissue culture plastics (TCPs) for modular tissue cultures, the majority of adjacent PMMA, some PLA but no PS particles aggregated. Human dermal fibroblasts (HDFs) could be directly seeded onto large (diameter: 30-100 µm) PMMA particles, but not small (diameter: 5-20 µm) PMMA, nor all the PLA and PS particles. During tissue cultures, HDFs migrated from the TCPs surfaces onto all the particles, while the clustered PMMA or PLA particles were colonized by HDFs into modular tissues with varying sizes. Further comparisons revealed that HDFs utilized the same cell bridging and stacking strategies to colonize single or clustered polymeric particles, and the finely controlled open pores, corners and gaps on 3D-printed PLA discs. These observed cell-scaffold interactions, which were then used to evaluate the adaptation of microcarrier-based cell expansion technologies for modular tissue manufacturing in DE.

[Research progress in treatment of Sjögren's syndrome by traditional Chinese medicine].

Sj9gren's syndrome(SS) is an autoimmune disease with glandular dysfunction caused by the massive infiltration of the exocrine glands by lymphocytes. The pathogenesis of this disease is related to the chronic inflammatory response of the exocrine glands due to excessive activation of B cells and T cells. In addition to dry mouth and eyes, SS can also cause damage to other organs and systems in the human body, seriously affecting the quality of life of patients. Traditional Chinese medicine(TCM) has definite clinical efficacy in the treatment of SS as it can alleviate symptoms and regulate immune disorders without causing adverse reactions, demonstrating high safety. This paper reviews the current status of preclinical and clinical trials about the TCM treatment of SS in the past decade. TCM mainly mitigates SS symptoms such as dry mouth, dry eyes, dry skin, and joint pain and improves the prognosis and quality of life of patients by regulating the abnormally activated B cells and T cells, inhibiting the autoimmune response, restoring the balance between pro-inflammatory and anti-inflammatory cytokines, and reducing the pathological damage caused by immune complexes to exocrine glands and joints in SS patients.

Sensing Material-Dependent Interference of Multiple Heavy Metal Ions: Experimental and Simulated Thermodynamics Study on Cu(II), Cd(II), and As(III) Electroanalysis.

Interference among multiple heavy metal ions (HMIs) is a significant problem that must be solved in electroanalysis, which extremely restricts the practical popularization of electrochemical sensors. However, due to the limited exploration of the intrinsic mechanism, it is still difficult to confirm the influencing factors. In this work, a series of experimental and theoretical electroanalysis models have been established to investigate the electroanalysis results of Cu(II), Cd(II), As(III), and their mixtures, which were based on the simple structure and stable coordination of nickel single-atom catalysts. X-ray absorption spectroscopy and density functional theory calculations were used to reveal the underlying detection mechanism of the 50-fold boosting effect of Cu(II) on As(III) while Cd(II) inhibits As(III). Combining the application of the thermodynamic model and Fourier transform infrared reflection, the specific interaction of the nanomaterials and HMIs on the interface is considered to be the fundamental source of the interference. This work opens up a new way of thinking about utilizing the unique modes of interplay between nanomaterials and HMIs to achieve anti-interference intelligent electrodes in stripping analysis.

Oral health in patients with dementia: A meta-analysis of comparative and observational studies.

OBJECTIVE: Poor oral health is common in dementia, but findings of epidemiological studies have been inconsistent. This meta-analysis examined oral health in patients with dementia diagnosed according to standardized diagnostic criteria. METHODS: Six international databases (PubMed, EMBASE, PsycINFO, Medline, Cochrane Library, and Web of Science) were searched from their commencement date until 8 November 2018. Oral health was measured by the Remaining Teeth (RT) and Decayed, Missing, and Filled Teeth (DMFT) Index. The mean differences (MD) and 95% confidence intervals (CI) of DMFT Index total and component scores were calculated using a random-effect model. RESULTS: Twenty-four studies were included for analyses. The pooled DMFT Index was 23.48 (95% CI: 22.34, 24.62), while the pooled score for each component was 2.38 (95% CI: 1.56, 3.20) in decayed teeth (DT), 18.39 (95% CI: 15.92, 20.87) in missing teeth (MT), 2.29 (95% CI: 0.62, 3.95) in filled teeth (FT), and 11.59 (95% CI: 9.14, 14.05) in RT. Compared to controls, people with dementia had significantly a higher DMFT Index total score (MD = 3.80, 95% CI: 2.21, 5.39, p < 0.00,001), and significantly lower number of RT (MD = -3.15, 95% CI: -4.23, -2.06, p < 0.00,001). Subgroup analyses revealed that higher DMFT Index score was significantly associated with year of survey (>2010), study design (case-control study), percentage of females (≤54.3), and the Mini Mental State Examination score (≤18.2). Higher MT score was significantly associated with study design (cross-sectional study), and lower FT score was significantly associated with year of survey (>2010). CONCLUSIONS: Oral health was significantly poorer in people with dementia compared with controls. Regular screening and effective treatment should be implemented for this population.

A Novel Sirolimus-eluting Biodegradable Magnesium-based Alloy Scaffold: Six-month Results In Porcine Peripheral Arteries.

PURPOSE: Magnesium-based alloy scaffold is a promising biodegradable stent due to its intrinsic mechanical performance and biocompatibility. Based on our preliminary experiments, we designed a novel sirolimus-eluting magnesium-based alloy scaffold. This work aimed to assess its safety and degradation performance in vivo. METHODS: The scaffolds were implanted in the lower limb arteries of Bama mini-pigs. Safety was defined as no immediate thrombosis or >30% residual stenosis, which was assessed with optical coherence tomography and digital subtraction angiography. Blood biochemical analyses were performed to evaluate hepatorenal toxicity. The degradation process of the scaffolds, the endothelialization, and lumen loss of the stented-vessels were detected with scanning electron microscopy, immunohistochemical, hematoxylin-eosin staining and optical coherence tomography. RESULTS: Twenty-four scaffolds were successfully implanted in six pigs with no signs of immediate thrombosis or >30% residual stenosis. The scaffolds were covered by endothelium at one month and absolutely resorbed at six months post implantation. Blood analysis showed that the hepatorenal function except for alanine aminotransferase and γ-glutamyl transpeptidase was normal. Obvious intimal hyperplasia and lumen loss were found in the stented vessels at three months, while the diameters and inner lumen areas of stented segments had increased significantly at six months (p.

Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials.

BACKGROUND: Results of previous studies on the safety and efficacy of adjunctive reboxetine for schizophrenia have been inconsistent. AIM: The aim of this study was to examine the efficacy and tolerability of reboxetine as an adjunct medication to antipsychotic treatment in a meta-analysis of randomized controlled trials (RCTs). METHODS: Two independent investigators extracted data for a random effects meta-analysis and assessed the quality of studies using risk of bias and the Jadad scale. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio (RR)±95% confidence intervals (CIs) were calculated. RESULTS: Nine RCTs (n=630) with double-blind design were identified. Reboxetine outperformed placebo in improving negative (9 RCTs, n=602, SMD: -0.47 [95% CI: -0.87, -0.07], p=0.02; I2=82%), but not the overall, positive, and general psychopathology scores. The significant therapeutic effect on negative symptoms disappeared in the sensitivity analysis after removing an outlying study and in 50% (6/12) of the subgroup analyses. Reboxetine outperformed placebo in reducing weight (3 RCTs, n=186, WMD: -3.83 kg, p=0.04; I2=92%) and body mass index (WMD: -2.23 kg/m2, p=0.04; I2=95%). Reboxetine caused dry mouth but was associated with less weight gain overall and weight gain of ≥7% of the initial weight. All-cause discontinuation and other adverse events were similar between reboxetine and placebo. CONCLUSION: Adjunctive reboxetine could be useful for attenuating antipsychotic-induced weight gain, but it was not effective in treating psychopathology including negative symptoms in schizophrenia.

Preparation and In vitro Evaluation of FDM 3D-Printed Ellipsoid-Shaped Gastric Floating Tablets with Low Infill Percentages.

The aim of the study is to investigate the feasibility of fabricating FDM 3D-printed gastric floating tablets with low infill percentages and the effect of infill percentage on the properties of gastric floating tablets in vitro. Propranolol hydrochloride was selected as a model drug, and drug-loaded polyvinyl alcohol (PVA) filaments were produced by hot melt extrusion (HME). Ellipsoid-shaped gastric floating tablets with low infill percentage of 15% and 25% (namely E-15 and E-25) were then prepared respectively by feeding the extruded filaments to FDM 3D printer. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) were employed to characterize the filaments and 3D-printed tablets, and a series of evaluations were performed to the 3D-printed tablets, including the weight variation, drug content, hardness, in vitro floating behavior, and drug release of the tablets. The SEM results showed that the drug-loaded filaments and 3D-printed tablets appeared intact without defects, and the printed tablets were composed of filaments deposited uniformly layer by layer. The model drug and the excipients were thermally stable under the process temperature of extruding and printing, with a small amount of drug crystals dispersing in the drug-loaded filaments and 3D-printed tablets. Both E-15 and E-25 could float on artificial gastric fluids without any lag time and released in a sustained manner. Compared with E-15, the E-25 presented less weight variation, higher tablet hardness, shorter floating time, and longer drug release time.

Light-Driven ATP Transmembrane Transport Controlled by DNA Nanomachines.

In nature, biological machines can perform sophisticated and subtle functions to maintain the metabolism of organisms. Inspired from these gorgeous works of nature, scientists have developed various artificial molecular motors and machines. However, selective transport of biomolecules across membrane has remained a great challenge. Here, we establish an ATP transport system by assembling photocontrolled DNA nanomachines into the artificial nanochannels. With alternant light irradiation, these ATP transport lines can selectively shepherd cargoes across the polymer membrane. These findings point to new opportunities for manipulating and improving the mass transportation and separation with light-controlled biomolecular motors, and can be used for other molecules and ions transmembrane transport powered by light.

Bioinspired Heterogeneous Ion Pump Membranes: Unidirectional Selective Pumping and Controllable Gating Properties Stemming from Asymmetric Ionic Group Distribution.

The creation of an artificial solid-state ion pump that mimics the delicate ion transport behaviors of a biological protein-based ion pump is drawing more and more research attention due to its potential applications in energy conversion, biosensor, and desalination. However, the reported bioinspired double-gated ion pump systems are generally very primary and can only realize nonselective ion pumping functions with no directionality and uncontrollable ion gating functions, which are far from their biological counterparts. To make the bioinspired device "smart" in a real sense, the implementation of high-level selectivity and directionality in the ion pumping process, while achieving great controllability in the ion gating process, is a necessity. Here, we developed a bioinspired heterogeneous ion pump membrane by combining block copolymer membrane sacrificial coating and plasma grafting technique. The system has unidirectional selective ion pumping and controllable ion gating properties. The introduction of asymmetric ionic group distribution is the key reason for its novel transport behaviors. Such a heterogeneous ion pump could not only provide a basic platform that potentially sparks further efforts to simulate the smart ion transport processes in living bodies but also promote the application of artificial nanofluidic devices in energy conversion, water treatment, and biosensing.

Aripiprazole for Tourette's syndrome: a systematic review and meta-analysis.

OBJECTIVE: To review the efficacy and safety of aripiprazole (ARI) for Tourette's syndrome (TS). METHODS: This review included randomized controlled trials (RCTs) of children and adolescents (6-18 years) with TS comparing ARI monotherapy with another monotherapies in relation to clinical improvement and adverse events. RESULTS: Six RCTs with a total of 528 subjects (ARI treatment group: n = 253; control group: n = 275) met the inclusion criteria. These included two RCTs (n = 255) that compared ARI monotherapy with tiapride (TIA). Tic symptoms control assessed by Yale Global Tic Severity Scale (Standard Mean Difference (SMD) = -0.38 (Confidence Interval (CI) = -1.32 to 0.56); I(2) = 90%, P = 0.42) revealed no significant differences between the two groups. Extrapyramidal symptoms were significantly different when ARI (1.5%) was compared with haloperidol (HAL) (43.5%). No significant group differences were found in the rates of nausea/vomiting, dizziness, and dry mouth between ARI and TIA (RR = 0.57 to 1.00 (95%CI = 0.14-4.20); I(2) = 0% to 69%, P = 0.35 to 1.00). CONCLUSION: This review found that ARI has similar efficacy to TIA and HAL for TS, while extrapyramidal symptoms were significantly less with ARI than with HAL. ARI can be considered as an alternative treatment option for TS.

Light-Controlled Ion Transport through Biomimetic DNA-Based Channels.

Light-controlled nanochannels are fabricated through self-assembling azobenzene-incorporated DNA (Azo-DNA) strands to regulate ion transport. By switching between collapsed and relaxed states using visible and ultraviolet light alternately, the Azo-DNA channels can be opened and closed because the conformation of Azo-DNA changes, that is, Azo-DNA is used as switchable controlling unit. In addition to sharing short response time and reversibility with other photoresponsive apparatuses, the Azo-DNA-based nanochannel system has advantages in good biocompatibility and versatile design, which could potentially be applied in light-controlled drug release, optical information storage, and logic networks.

Psychological well-being status among medical and dental students in Makkah, Saudi Arabia: a cross-sectional study.

OBJECTIVES: Medical and dental students experience poor psychological well-being relative to their peers. This study aimed to assess the psychological well-being among medical and dental students in Saudi Arabia, identify the high-risk groups and assess the association between the psychological well-being and the academic performance. METHODS: In this cross-sectional study, 422 preclinical medical and dental students at Umm Al-Qura University, Saudi Arabia, were recruited to assess their depression, anxiety, stress, self-efficacy and satisfaction with life levels using 21-items Depression Anxiety Stress Scale (DASS-21), General Self-Efficacy (GSE) scale and Satisfaction With Life Scale (SWLS). Students' academic weighted grades were obtained later. Descriptive statistics and univariate general linear model were used to analyse data. RESULTS: High levels of depression (69.9%), anxiety (66.4%) and stress (70.9%) were indicated, whereas self-efficacy (mean = 27.22, sd = 4.85) and life satisfaction (mean = 23.60, sd = 6.37) were within the normal range. Female medical students had higher psychological distress in contrast to dental students. In general, third-year students were more depressed and stressed in comparison with second-year students, except for stress among dental students. Moreover, all females had higher self-efficacy than males. Life satisfaction was higher within the second-year and high family income students. Depression was the only psychological variable correlated with the academic performance. CONCLUSION: High levels of psychological distress were found. Female medical students had higher psychological distress than males, whereas male dental students had higher distress than female. Medical students at third year were more depressed and stressed. Dental students were more depressed in the third year, but more stressed in the second year. Attention should be directed towards reducing the alarming levels of depression, anxiety and stress among medical and dental students.

The impact of a self-development coaching programme on medical and dental students' psychological health and academic performance: a randomised controlled trial.

BACKGROUND: Psychological distress is well-documented worldwide among medical and dental students. Few studies have assessed the impact of self-development coaching programs on the students' psychological health. The aim of the study was to evaluate the effect of a self-development coaching programme on the psychological health and academic performance of preclinical medical and dental students at Umm Al-Qura University, Saudi Arabia. METHODS: Four-hundred and twenty-two participants (n = 422, 20-22 years) fulfilled the study requirements and were invited into a parallel-randomised controlled trial that was partially blinded. Participants were stratified by faculty, gender, and academic year, and then randomised. A total of 156 students participated in the intervention group (IG) and 163 students participated in the control group (CG). The IG received the selfdevelopment programme, involving skills and strategies aimed to improve students' psychological health and academic performance, through a two-day workshop. Meanwhile, the CG attended an active placebo programme focussing on theoretical information that was delivered through a five-hour workshop. Both programmes were conducted by the same presenter during Week 1 of the second semester of the 2012-2013 academic year. Data were gathered immediately before (T1), one week after (T2) and five weeks (T3) after the intervention. Psychological health was measured using the Depression Anxiety Stress Scale (DASS-21), the General Self-Efficacy (GSE), and the Satisfaction With Life Scale (SWLS). Academic performance was measured using students' academic weighted grades (WG). Student cognitive and emotional perceptions of the intervention were measured using the Credibility/Expectancy Questionnaire (CEQ). RESULTS: Data from 317 students, who completed the follow ups, were analysed across the three time periods (IG, n = 155; CG, n = 162). The baseline variables and demographic data of the IG and CG were not significantly different. The IG showed short-term significant reductions in depression and anxiety in compared to CG from T1 to T2. The short-term changes in stress, GSE and SWLS of the IG were not significantly different from those of the CG. While both groups showed a significant change on most of the psychological variables from T1 to T3, no significant differences were found between the groups in this period. In addition, no significant difference was found in WG between the IG and CG after the intervention. No harms relevant to the intervention were reported. CONCLUSION: The investigated self-development coaching programme showed only a short-term improvement on depression and anxiety compared with an active control. There was no effect of the intervention on academic performance. TRIAL REGISTRATION: ACTRN12614000896673.

Endoplasmic reticulum stress regulates rat mandibular cartilage thinning under compressive mechanical stress.

Compressive mechanical stress-induced cartilage thinning has been characterized as a key step in the progression of temporomandibular joint diseases, such as osteoarthritis. However, the regulatory mechanisms underlying this loss have not been thoroughly studied. Here, we used an established animal model for loading compressive mechanical stress to induce cartilage thinning in vivo. The mechanically stressed mandibular chondrocytes were then isolated to screen potential candidates using a proteomics approach. A total of 28 proteins were identified that were directly or indirectly associated with endoplasmic reticulum stress, including protein disulfide-isomerase, calreticulin, translationally controlled tumor protein, and peptidyl-prolyl cis/trans-isomerase protein. The altered expression of these candidates was validated at both the mRNA and protein levels. The induction of endoplasmic reticulum stress by mechanical stress loading was confirmed by the activation of endoplasmic reticulum stress markers, the elevation of the cytoplasmic Ca(2+) level, and the expansion of endoplasmic reticulum membranes. More importantly, the use of a selective inhibitor to block endoplasmic reticulum stress in vivo reduced the apoptosis observed at the early stages of mechanical stress loading and inhibited the proliferation observed at the later stages of mechanical stress loading. Accordingly, the use of the inhibitor significantly restored cartilage thinning. Taken together, these results demonstrated that endoplasmic reticulum stress is significantly activated in mechanical stress-induced mandibular cartilage thinning and, more importantly, that endoplasmic reticulum stress inhibition alleviates this loss, suggesting a novel pharmaceutical strategy for the treatment of mechanical stress-induced temporomandibular joint diseases.

Construction of catalyst layer network structure for proton exchange membrane fuel cell derived from polymeric dispersion.

A rational design of the structure of catalyst layer (CL) is required for proton exchange membrane fuel cells to attain outstanding performance and excellent stability. It is crucial to have a profound comprehension of the correlations existing between the properties (catalyst ink), network structures of CL and proton exchange membrane fuel cells' performance for the rational design of the structure of CL. This study deeply investigates the effects of a series of alcohol solvents on the properties and network structure of CL. The results demonstrate that the CL aggregates in higher ε solution show smaller particle sizes, and the sulfonic acid groups (∼SO3H) tend to extend more outward due to the strong dissociation. A more continuous and homogeneous ionomer distribution around Pt/C aggregates is observed in the CL, which improves the electrochemically active surface area (ECSA) and performance of the electrode. But, the electrode has a poor performance at high current density regions due to the mass transfer resistance. Based on this, a two-step solvent control strategy is proposed to maintain uniform ionomer and aggerates distribution and optimize the mass transfer for CL. The performance of the cell improves from 0.555 V to 0.615 V at 2000 mA·cm-2.

Rapamycin Inhibits Osteoclastogenesis and Prevents LPS-Induced Alveolar Bone Loss by Oxidative Stress Suppression.

Periodontitis is a progressive inflammatory skeletal disease characterized by periodontal tissue destruction, alveolar bone resorption, and tooth loss. Chronic inflammatory response and excessive osteoclastogenesis play essential roles in periodontitis progression. Unfortunately, the pathogenesis that contributes to periodontitis remains unclear. As a specific inhibitor of the mTOR (mammalian/mechanistic target of rapamycin) signaling pathway and the most common autophagy activator, rapamycin plays a vital role in regulating various cellular processes. The present study investigated the effects of rapamycin on osteoclast (OC) formation in vitro and its effects on the rat periodontitis model. The results showed that rapamycin inhibited OC formation in a dose-dependent manner by up-regulating the Nrf2/GCLC signaling pathway, thus suppressing the intracellular redox status, as measured by 2',7'-dichlorofluorescein diacetate and MitoSOX. In addition, rather than simply increasing the autophagosome formation, rapamycin increased the autophagy flux during OC formation. Importantly, the anti-oxidative effect of rapamycin was regulated by an increase in autophagy flux, which could be attenuated by blocking autophagy with bafilomycin A1. In line with the in vitro results, rapamycin treatment attenuated alveolar bone resorption in rats with lipopolysaccharide-induced periodontitis in a dose-dependent manner, as assessed by micro-computed tomography, hematoxylin-eosin staining, and tartrate-resistant acid phosphatase staining. Besides, high-dose rapamycin treatment could reduce the serum levels of proinflammatory factors and oxidative stress in periodontitis rats. In conclusion, this study expanded our understanding of rapamycin's role in OC formation and protection from inflammatory bone diseases.