Long-term di-(2-ethylhexyl) phthalate exposure reduces sorafenib treatment efficacy by enhancing mesenchymal transition in hepatocellular carcinoma.

Di(2-ethylhexyl) phthalate (DEHP) is a worldwide common plasticizer. Nevertheless, DEHP is easily leached out to the environment due to the lack of covalent bonds with plastic. High dose of DEHP exposure is often observed in hemodialysis patients because of the continual usage of plastic medical devices. Although the liver is the major organ that catabolizes DEHP, the impact of long-term DEHP exposure on the sensitivity of liver cancer to chemotherapy remains unclear. In this study, we established long-term DEHP-exposed hepatocellular carcinoma (HCC) cells and two NOD/SCID mice models to investigate the effects and the underlying mechanisms of long-term DEHP exposure on chemosensitivity of HCC. The results showed long-term DEHP exposure potentially increased epithelial-mesenchymal transition (EMT) in HCC cells. Next generation sequencing showed that long-term DEHP exposure increased cell adhesion/migratory related genes expression and blunted sorafenib treatment induced genes alterations. Long-term exposure to DEHP reduced the sensitivity of HCC cells to sorafenib-induced anti-migratory effect by enhancing the EMT transcription factors (slug, twist, and ZEB1) and mesenchymal protein (vimentin) expression. In NOD/SCID mice model, we showed that long-term DEHP-exposed HCC cells exhibited higher growth rate. Regarding the anti-HCC effects of sorafenib, subcutaneous HuH7 tumor grew slowly in sorafenib-treated mice. Nonetheless, the anti-tumor growth effect of sorafenib was not observed in long-term DEHP-exposed mice. Higher mesenchymal markers and proliferating cell nuclear antigen (PCNA) expression were found in sorafenib-treated long-term DEHP-exposed mice. In conclusion, long-term DEHP exposure promoted migratory activity in HCC cells and decreased sorafenib sensitivity in tumor-bearing mice.

Structure-guided antibody cocktail for prevention and treatment of COVID-19.

Development of effective therapeutics for mitigating the COVID-19 pandemic is a pressing global need. Neutralizing antibodies are known to be effective antivirals, as they can be rapidly deployed to prevent disease progression and can accelerate patient recovery without the need for fully developed host immunity. Here, we report the generation and characterization of a series of chimeric antibodies against the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Some of these antibodies exhibit exceptionally potent neutralization activities in vitro and in vivo, and the most potent of our antibodies target three distinct non-overlapping epitopes within the RBD. Cryo-electron microscopy analyses of two highly potent antibodies in complex with the SARS-CoV-2 spike protein suggested they may be particularly useful when combined in a cocktail therapy. The efficacy of this antibody cocktail was confirmed in SARS-CoV-2-infected mouse and hamster models as prophylactic and post-infection treatments. With the emergence of more contagious variants of SARS-CoV-2, cocktail antibody therapies hold great promise to control disease and prevent drug resistance.

Elevated Hippocampal CRMP5 Mediates Chronic Stress-Induced Cognitive Deficits by Disrupting Synaptic Plasticity, Hindering AMPAR Trafficking, and Triggering Cytokine Release.

Chronic stress is a critical risk factor for developing depression, which can impair cognitive function. However, the underlying mechanisms involved in chronic stress-induced cognitive deficits remain unclear. Emerging evidence suggests that collapsin response mediator proteins (CRMPs) are implicated in the pathogenesis of psychiatric-related disorders. Thus, the study aims to examine whether CRMPs modulate chronic stress-induced cognitive impairment. We used the chronic unpredictable stress (CUS) paradigm to mimic stressful life situations in C57BL/6 mice. In this study, we found that CUS-treated mice exhibited cognitive decline and increased hippocampal CRMP2 and CRMP5 expression. In contrast to CRMP2, CRMP5 levels strongly correlated with the severity of cognitive impairment. Decreasing hippocampal CRMP5 levels through shRNA injection rescued CUS-induced cognitive impairment, whereas increasing CRMP5 levels in control mice exacerbated memory decline after subthreshold stress treatment. Mechanistically, hippocampal CRMP5 suppression by regulating glucocorticoid receptor phosphorylation alleviates chronic stress-induced synaptic atrophy, disruption of AMPA receptor trafficking, and cytokine storms. Our findings show that hippocampal CRMP5 accumulation through GR activation disrupts synaptic plasticity, impedes AMPAR trafficking, and triggers cytokine release, thus playing a critical role in chronic stress-induced cognitive deficits.

A Novel Convolutional Neural Network Model as an Alternative Approach to Bowel Preparation Evaluation Before Colonoscopy in the COVID-19 Era: A Multicenter, Single-Blinded, Randomized Study.

INTRODUCTION: Adequate bowel preparation is key to a successful colonoscopy, which is necessary for detecting adenomas and preventing colorectal cancer. We developed an artificial intelligence (AI) platform using a convolutional neural network (CNN) model (AI-CNN model) to evaluate the quality of bowel preparation before colonoscopy. METHODS: This was a colonoscopist-blinded, randomized study. Enrolled patients were randomized into an experimental group, in which our AI-CNN model was used to evaluate the quality of bowel preparation (AI-CNN group), or a control group, which performed self-evaluation per routine practice (control group). The primary outcome was the consistency (homogeneity) between the results of the 2 methods. The secondary outcomes included the quality of bowel preparation according to the Boston Bowel Preparation Scale (BBPS), polyp detection rate, and adenoma detection rate. RESULTS: A total of 1,434 patients were enrolled (AI-CNN, n = 730; control, n = 704). No significant difference was observed between the evaluation results ("pass" or "not pass") of the groups in the adequacy of bowel preparation as represented by BBPS scores. The mean BBPS scores, polyp detection rate, and adenoma detection rate were similar between the groups. These results indicated that the AI-CNN model and routine practice were generally consistent in the evaluation of bowel preparation quality. However, the mean BBPS score of patients with "pass" results were significantly higher in the AI-CNN group than in the control group, indicating that the AI-CNN model may further improve the quality of bowel preparation in patients exhibiting adequate bowel preparation. DISCUSSION: The novel AI-CNN model, which demonstrated comparable outcomes to the routine practice, may serve as an alternative approach for evaluating bowel preparation quality before colonoscopy.

Ideal Nasal Radix Position in Fluctuating Facial Asymmetry.

BACKGROUND: Augmentation rhinoplasty had become increasingly popular among Asians. Failure to recognize nasal deviation before surgery may engender unsatisfactory outcomes because the deviation becomes prominently visible after surgery due to the central position of the nose. Ideal nasal radix positioning has yet to be addressed. The head position affects facial asymmetry judgements; however, its effect on rhinoplasty has never been studied. This study determined the ideal nasal radix position in facial fluctuating asymmetry and investigated the effects of the natural head position (NHP) on nasal deviation perceptions. METHODS: A survey was conducted to compare different head and nasal radix horizontal positions using images of patients who underwent augmentation rhinoplasty. Images were retouched using editing software to adjust the head and nasal radix positions. The survey was performed using questionnaires involving 3 plastic surgeons and 3 laypersons, who were asked to determine the presence of nasal deviation and select the ideal nasal radix position among the retouched images. RESULTS: Twenty patients who underwent primary rhinoplasty were included in this study. The recognition of nasal deviation was significantly higher in the NHP than in the compensatory head position. The surgeons and the laypersons considered the midsagittal line the most appropriate position of the nasal radix. CONCLUSIONS: Facial analysis for augmentation rhinoplasty should be performed with the patient's head in the NHP to prevent nasal deviation masking. The preferred nasal radix position in facial fluctuating asymmetry is the midsagittal line.Level of Evidence: Level V, descriptive study.

Ketogenic Diet Enhances the Cholesterol Accumulation in Liver and Augments the Severity of CCl4 and TAA-Induced Liver Fibrosis in Mice.

Persistent chronic liver diseases increase the scar formation and extracellular matrix accumulation that further progress to liver fibrosis and cirrhosis. Nevertheless, there is no antifibrotic therapy to date. The ketogenic diet is composed of high fat, moderate to low-protein, and very low carbohydrate content. It is mainly used in epilepsy and Alzheimer's disease. However, the effects of the ketogenic diet on liver fibrosis remains unknown. Through ketogenic diet consumption, ß-hydroxybutyrate (bHB) and acetoacetate (AcAc) are two ketone bodies that are mainly produced in the liver. It is reported that bHB and AcAc treatment decreases cancer cell proliferation and promotes apoptosis. However, the influence of bHB and AcAc in hepatic stellate cell (HSC) activation and liver fibrosis are still unclear. Therefore, this study aimed to investigate the effect of the ketogenic diet and ketone bodies in affecting liver fibrosis progression. Our study revealed that feeding a high-fat ketogenic diet increased cholesterol accumulation in the liver, which further enhanced the carbon tetrachloride (CCl4)- and thioacetamide (TAA)-induced liver fibrosis. In addition, more severe liver inflammation and the loss of hepatic antioxidant and detoxification ability were also found in ketogenic diet-fed fibrotic mouse groups. However, the treatment with ketone bodies (bHB and AcAc) did not suppress transforming growth factor-ß (TGF-ß)-induced HSC activation, platelet-derived growth factor (PDGF)-BB-triggered proliferation, and the severity of CCl4-induced liver fibrosis in mice. In conclusion, our study demonstrated that feeding a high-fat ketogenic diet may trigger severe steatohepatitis and thereby promote liver fibrosis progression. Since a different ketogenic diet composition may exert different metabolic effects, more evidence is necessary to clarify the effects of a ketogenic diet on disease treatment.

Effects of Dynamic Stretching Combined With Static Stretching, Foam Rolling, or Vibration Rolling as a Warm-Up Exercise on Athletic Performance in Elite Table Tennis Players.

CONTEXT: Warm-up exercise is an essential preexercise routine for athletes to optimize performance. However, the benefits of combined warm-up protocols remain unclear. OBJECTIVE: This comparative study investigated the acute effects of dynamic stretching (DS) followed by static stretching (SS), self-myofascial release using a foam rolling (FR) device, or vibration foam rolling (VFR) as a warm-up exercise to improve flexibility, power, agility, and specific skills in elite table tennis players. DESIGN: A crossover study. SETTING: University. PARTICIPANTS: Twenty-three elite table tennis players. INTERVENTIONS: Players completed 3 different interventions in a random order (DS + SS, DS + FR, and DS + VFR). The target muscle groups included the bilateral posterior calf, posterior thigh, anterior thigh, back, and shoulder. MAIN OUTCOME MEASURES: Sit-and-reach test for flexibility, board jump test for lower-extremity power, medicine ball throw test for upper-extremity power, Edgren Side Step Test for agility, and ball speed of table tennis was assessed before and after intervention. RESULTS: After intervention, significant increases in flexibility (15.2%, 20.4%, and 23.8%); lower-limb power (4.5%, 6.6%, and 6.3%); upper-limb power (9.6%, 8.5%, and 9.1%); and ball speed (7.4%, 7.6%, and 7.7%) were observed for DS + SS, DS + FR, and DS + VFR, respectively (all P < .001). In addition, only DS coupled with FR (5.1%) and DS in conjunction with VFR (2.7%) significantly improved agility (P < .001). However, no significant improvements in agility were observed after DS + SS. In addition, no one protocol was superior to the other in all outcomes. CONCLUSION: The authors suggest that a combination of DS with FR or VFR as warm-up exercises significantly improved flexibility, power, ball speed, in addition to agility in elite table tennis players. Coach and athletic professionals may take this information into account for choosing more effective warm-up protocols to enhance performance.

Effects of Group Reminiscence Therapy on Agitated Behavior and Quality of Life in Taiwanese Older Adults With Dementia.

The purpose of the current study was to evaluate short- and long-term effects of group reminiscence on agitated symptoms and quality of life (QOL) for individuals with dementia. A quasi-experimental study using a repeated-measures design was conducted in 43 residents with dementia. Participants received a 50-minute group reminiscence therapy session once per week for 10 weeks. Outcomes were measured 1 week before, 1 week after, and at 3 months postintervention. Results showed no significant difference on the overall agitated behavior of participants. However, verbally aggressive behavior decreased significantly (p = 0.025), whereas intentional falling (p = 0.025), hoarding (p = 0.021), and akathisia (p = 0.027) significantly decreased in the short term. Participation in group reminiscence therapy significantly improved QOL (p < 0.001) across time periods for individuals with dementia. The findings provide information for professional and nonprofessional caregivers of individuals with specific agitated behaviors to improve their QOL. [Journal of Psychosocial Nursing and Mental Health Services, 57(8), 30-36.].

Effect of green manure amendment on herbicide pendimethalin on soil.

Manure amendment in agricultural practice can have a large effect on herbicide dissipation because the period of manure plowing is close to the period of herbicide application. In addition, manure amendment is among the frequently encountered options in ameliorating pesticide pollution. In this research, the dissipation of the herbicide pendimethalin was examined after amendment with two common green manures, Lupinus luteus (L) or Cosmos bipinnatus (C), for 110 days in pH 5.2 and 7.7 soils (Sankengtzu [Sk] and Erhlin [Eh] soil, respectively). The microbial activity and ecology changes were examined by using Biolog EcoPlate and denaturing gradient gel electrophoresis (DGGE). In Sk soil, the half-lives of pendimethalin with L, C, and blank treatment were 49.0, 54.9, and 62.2 days, respectively, whereas that in Eh soil they were 46.3, 52.6, and 34.8 days, respectively. Pendimethalin dissipated quickly in more neutral soil (Eh soil), but the addition of manure can only increase the dissipation rate in acidic soil (Sk soil), indicating that the amendment of manures exerted different effect in pendimethalin dissipation rates in different pH soils. The application of pendimethalin and/or manure altered the microbial community activity after 24 h of incubation. After 110 days, the microbial community activities in green manure-amended soil were more similar to that with blank than pendimethalin treatment in both types of soils. In comparison with treatment C, microbial communities were more similar between treatment L and blank, indicating the superior effect over pendimethalin on microbial communities when applying Lupinus luteus. The research showed that the application of herbicide pendimethalin changed soil microbial community, and the amendment of manures exerted different effect in pendimethalin dissipation rates in different pH soils. It is assumed that the change in dissipation rates was originated from the microbial community change after different manure amendment.

LncRNA Litchi is a regulator for harmonizing maturity and resilient functionality in spinal motor neurons.

Long noncoding RNAs (lncRNAs) play pivotal roles in modulating gene expression during development and disease. Despite their high expression in the central nervous system (CNS), understanding the precise physiological functions of CNS-associated lncRNAs has been challenging, largely due to the in vitro-centric nature of studies in this field. Here, utilizing mouse embryonic stem cell (ESC)-derived motor neurons (MNs), we identified an unexplored MN-specific lncRNA, Litchi (Long Intergenic RNAs in Chat Intron). By employing an "exon-only" deletion strategy in ESCs and a mouse model, we reveal that Litchi deletion profoundly impacts MN dendritic complexity, axonal growth, and altered action potential patterns. Mechanistically, voltage-gated channels and neurite growth-related genes exhibited heightened sensitivity to Litchi deletion. Our Litchi-knockout mouse model displayed compromised motor behaviors and reduced muscle strength, highlighting Litchi's critical role in motor function. This study unveils an underappreciated function of lncRNAs in orchestrating MN maturation and maintaining robust electrophysiological properties.

Dietary rice bran attenuates hepatic stellate cell activation and liver fibrosis in mice through enhancing antioxidant ability.

Various endogenous and exogenous stimuli can result in an inflammatory response and collagen deposition in the liver, which affect liver function and increase the risk of developing liver cirrhosis and cancer. Rice bran, the main by-product of rice milling, contains various nutrients which possess hepatoprotective activities. In this study, we investigated the effects of rice bran on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Mice were fed a rice-bran-containing diet (10% rice bran w/w) or a standard diet with or without an injection of 20% CCl4 to induce liver fibrosis. Our results showed that feeding a rice-bran-containing diet could alleviate CCl4-induced liver damage, collagen deposition, and expressions of fibrosis-related genes, including α-smooth muscle actin (α-SMA), collagen 1a2 (COL1A2), and transforming growth factor-ß (TGF-ß) in liver tissues. Moreover, consumption of rice bran enhanced phase II detoxification and antioxidant gene expressions, including Gsta3, Gstp1, Catalase, SOD1, SOD2, and SOD3. Treatment with γ-oryzanol, the major bioactive compound in rice bran, decreased the sensitivity of hepatic stellate cells (HSCs) to TGF-ß1-induced α-SMA, COL1A2, and phosphorylated smad2 expressions. In conclusion, a rice-bran-containing diet may have beneficial effects on liver fibrogenesis through increased antioxidant and detoxification activities. γ-Oryzanol, the major bioactive compound of rice bran, can inhibit activation of HSCs.

A prospective study of psychological adjustment during and after forehead flap nasal reconstruction.

The psychological effects of staged nasal reconstruction with a forehead flap were prospectively investigated. Thirty-three patients underwent nasal reconstruction with forehead flaps between March 2017 and July 2020. Three questionnaires were used to assess psychosocial functioning before surgery (time 1), 1 week after forehead flap transfer (time 2), 1 week after forehead flap division (time 3), and after refinement procedures (time 4). The patients were categorized into three groups according to the severity of nasal defects. Between- and within-group comparisons were conducted. All patients reported increased satisfaction with their appearance during nasal reconstruction. For most patients, levels of distress and social avoidance were highest before reconstruction (time 1). Both levels decreased as reconstruction advanced, and were significantly improved by times 3 and 4. The stage of reconstruction had a greater effect on these levels than did severity of nasal defect. Nasal reconstruction with forehead flap is beneficial physically and psychologically. Psychological evaluation before and after surgery facilitates patient-surgeon interactions and further enhances outcomes.

Treatment with a new barbituric acid derivative suppresses diet-induced metabolic dysfunction and non-alcoholic fatty liver disease in mice.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, often accompanied by obesity, diabetes, and increased risks of depression and anxiety. Currently, there are no FDA-approved drugs to treat NAFLD and its related systemic symptoms. Previously, we identified a new barbituric acid derivative (BA-5) that expressed effectiveness against fibrosis and drug-resistant hepatocellular carcinoma. AIMS: This study investigated the potential of BA-5 against high-fat diet (HFD)-induced NAFLD and mood disorders in mice. MAIN METHODS: Six-weeks-old male C57BL/6 mice were fed with a 45 % HFD for 8 weeks to induce NAFLD and associated metabolic disorders. Mice were treated with a BA-5 and the therapeutic effects and the underlying molecular mechanisms were investigated. KEY FINDINGS: Administration of BA-5 significantly reduced serum levels of alanine aminotransferase (ALT), low-density lipoprotein (LDL), fatty acids (FA), and triglycerides (TG) in HFD-fed mice. BA-5 treatment decreased expressions of hepatic lipogenesis-related markers (acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and ATP-citrate lyase (ACLY)), increased fatty acid oxidation markers (carnitine palmitoyltransferase 1A (CPT1A) and acyl-CoA oxidase 1 (ACOX1)), and attenuated hepatic fat accumulation in HFD-fed mice. Moreover, HFD-induced adipocyte size enlargement and activation of lipolysis markers such as phosphorylated (p)-hormone-sensitive lipase (HSL) 565, p-HSL 660, and perilipin were inhibited in BA-5-treated mice. Notably, HFD-induced anxiety- and depression-like behaviors significantly improved in the BA-5 treated group through enhanced anti-inflammatory responses in the hippocampus. SIGNIFICANCE: This study provides new insights into clinical therapeutic strategies of barbituric acid derivatives for HFD-induced NAFLD and associated mood disturbances.

Recommendations and guidelines for endoscope reprocessing: Current position statement of digestive endoscopic society of Taiwan.

Reprocessing of gastrointestinal (GI) endoscopes and accessories is an essential part of patient safety and quality control in GI endoscopy centers. However, current endoscopic reprocessing guidelines or procedures are not adequate to ensure patient-safe endoscopy. Approximately 5.4 % of the clinically used duodenoscopes remain contaminated with high-concern microorganisms. Thus, the Digestive Endoscopy Society of Taiwan (DEST) sets standards for the reprocessing of GI endoscopes and accessories in endoscopy centers. DEST organized a task force working group using the guideline-revision process. These guidelines contain principles and instructions of step-by-step for endoscope reprocessing. The updated guidelines were established after a thorough review of the existing global and local guidelines, systematic reviews, and health technology assessments of clinical effectiveness. This guideline aims to provide detailed recommendations for endoscope reprocessing to ensure adequate quality control in endoscopy centers.

Developmental Coordination Disorder and Unhealthy Weight Status in Taiwanese Children: The Roles of Sex and Age.

This study aimed to provide up-to-date information regarding the estimated prevalence of developmental coordination disorder (DCD) in Taiwanese children. Their unhealthy weight status was also examined, as well as the roles of sex and age. This cross-sectional study recruited 825 children aged between 4 and 12 years and categorized them into either typically developing children (TD, >16th percentile) or children at risk for DCD (rDCD, ≤16th percentile) based on the result of the Movement Assessment Battery for Children-2nd edition. Body mass index was calculated to determine weight status (i.e., normal weight, underweight, overweight, and obesity). The estimated prevalence of rDCD was 9.7%. There were significantly more boys in the rDCD groups (p < 0.001). Additionally, preschool children with rDCD were at greater risk for being underweight. However, there was no significant group difference which was found for overweight/obesity. A lower prevalence of rDCD was found in this study. Nevertheless, children with rDCD may be more likely to be underweight in early childhood. Early intervention should be provided to target this population.

Dietary oxidized frying oil activates hepatic stellate cells and accelerates the severity of carbon tetrachloride- and thioacetamide-induced liver fibrosis in mice.

Deep-frying is a common cooking practice worldwide, and after repeated heating's, the oil undergoes various chemical reactions, including hydrolysis, polymerization, lipid oxidation, and the Maillard reaction. Studies have pointed out that oxidized dietary frying oil may cause teratogenesis in mice and increase cancer and cardiovascular risks. The liver is the main organ involved in dietary nutrient catabolism, detoxification, bile production, and lipid metabolism. Nevertheless, the effects of oxidized frying oil exposure on the activation of hepatic stellate cells (HSCs) and liver fibrosis are still unclear. In this study, we showed that exposure to oxidized frying oil enhanced the sensitivity of HSCs to transforming growth factor (TGF)-ß1-induced α-smooth muscle actin (α-SMA), collagen 1a2, collagen 1a1, metalloproteinase-2, and phosphorylated smad2/3 activation. In both carbon tetrachloride (CCl4)- and thioacetamide (TAA)-induced liver fibrosis mouse models, we showed that long-term administration of a 10% fried oil-containing diet significantly upregulated fibrogenesis genes expression and deposition of hepatic collagen. Furthermore, long-term fried oil exposure not only promoted macrophage infiltration and increased inflammatory-related gene expression, but also accumulated excess cholesterol and lipid peroxidation in the liver tissues. In conclusion, our study demonstrated that feeding a fried oil-containing diet may trigger TGF-ß1-induced HSCs activation and thereby promote liver damage and fibrosis progression through enhancing the inflammatory response and lipid peroxidation.

Setting up a three-stage pre-endoscopy triage during the coronavirus disease 2019 pandemic: A multicenter observational study.

Objectives: Between May and July 2021, the coronavirus disease 2019 (COVID-19) pandemic led to a sharp surge in community transmission in Taiwan. We present a three-stage restructuring process of pre-endoscopy triage at the beginning of the pandemic, which can support urgent endoscopic procedures while protecting endoscopy staff. Methods: The pre-endoscopy triage framework was set up with three checkpoints at the hospital entrance, outpatient department, and endoscopy unit, with a specific target patient population and screening methods. Relevant data included the number of endoscopic procedures performed, outpatient department visits, and performing screening methods such as temperature measurement, travel, occupation, contact, and clustering history checking, polymerase chain reaction assay, and rapid antigen test. Results: Forehead temperature measurement and verification of travel, occupation, contact, and clustering history provided rapid, easy, and early mass screening of symptomatic patients at the hospital entrance. During the pandemic, outpatient department visits and endoscopic procedures decreased by 37% and 64%, respectively. The pre-endoscopy screening methods used displayed regional variations in COVID-19 prevalence. Among 16 endoscopy units with a community prevalence of ≥ 31.04 cases per 100,000 residents, 12 (75%) used polymerase chain reaction assay and four (25%) used rapid antigen test to identify asymptomatic patients before endoscopy. Of 6540 pre-endoscopy screening patients, 15 (0.23%) tested positive by laboratory testing. No endoscopy-related nosocomial COVID-19 infections were reported during the pandemic. Conclusions: We present a three-stage pre-endoscopy triage based on the local laboratory capacity, medical resources, and community prevalence. These measures could be useful during the COVID-19 pandemic.

Sequential deacetylation/self-gelling chitin hydrogels and scaffolds functionalized with fucoidan for enhanced BMP-2 loading and sustained release.

Bone morphogenetic protein 2 (BMP-2) is a potent osteoinductive factor that promotes bone formation. A major obstacle to the clinical application of BMP-2 is its inherent instability and complications caused by its rapid release from implants. Chitin based materials have excellent biocompatibility and mechanical properties, making them ideal for bone tissue engineering applications. In this study, a simple and easy method was developed to spontaneously form deacetylated ß-chitin (DAC-ß-chitin) gels at room temperature through a sequential deacetylation/self-gelation process. The structural transformation of ß-chitin to DAC-ß-chitin leads to the formation of self-gelling DAC-ß-chitin, from which hydrogels and scaffolds were prepared. Gelatin (GLT) accelerated the self-gelation of DAC-ß-chitin and increased the pore size and porosity of the DAC-ß-chitin scaffold. The DAC-ß-chitin scaffolds were then functionalized with a BMP-2-binding sulfate polysaccharide, fucoidan (FD). Compared with ß-chitin scaffolds, FD-functionalized DAC-ß-chitin scaffolds showed higher BMP-2 loading capacity and more sustainable release of BMP-2, and thus had better osteogenic activity for bone regeneration.

MiR34 contributes to spinal muscular atrophy and AAV9-mediated delivery of MiR34a ameliorates the motor deficits in SMA mice.

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by the selective loss of spinal motor neurons (MNs) and concomitant muscle weakness. Mutation of SMN1 is known to cause SMA, and restoring SMN protein levels via antisense oligonucleotide treatment is effective for ameliorating symptoms. However, this approach is hindered by exorbitant costs, invasive procedures, and poor treatment responses of some patients. Here, we seek to circumvent these hurdles by identifying reliable biomarkers that could predict treatment efficacy. We uncovered that MiR34 exhibits consistent downregulation during SMA progression in both human and rodent contexts. Importantly, Mir34 family-knockout mice display axon swelling and reduced neuromuscular junction (NMJ) endplates, recapitulating SMA pathology. Introducing MiR34a via scAAV9 improved the motor ability of SMNΔ7 mice, possibly by restoring NMJ endplate size. Finally, we observed a consistent decreasing trend in MiR34 family expression in the cerebrospinal fluid (CSF) of type I SMA patients during the loading phase of nusinersen treatment. Baseline CSF MiR34 levels before nusinersen injection proved predictive of patient motor skills 1 year later. Thus, we propose that MiR34 may serve as a biomarker of SMA since it is associated with the pathology and can help evaluate the therapeutic effects of nusinersen.

Biodegradable Nanoparticles Prepared from Chitosan and Casein for Delivery of Bioactive Polysaccharides.

Ophiopogon japonicus polysaccharides (OJPs) have great anti-inflammation and immunomodulatory abilities. However, the low bioavailability of OJPs reduces its applicability in the biomedical and pharmaceutical fields. Chitosan (CS) has excellent mucoadhesive properties and absorption-enhancing ability in oral administration. Casein hydrolysate (CL) has good interfacial diffusivity and emulsifying ability, and can interact with polysaccharides to form complexes combining the individual properties of both. Therefore, chitosan and casein hydrolysate are good candidates for developing nanoformulations for oral delivery. In this study, bioactive polysaccharides (OJPs), CS and CL, were combined to prepare CS/OJPs/CL co-assembled biodegradable nanoparticles. The interactions between polysaccharides (CS and OJPs) and peptide (CL) resulted in the formation of nanoparticles with an average particle size of 198 nm and high OJPs loading efficiency. The colloidal properties of the nanoparticles were pH-dependent, which were changed significantly in simulated digestive fluid at different pH values. OJPs released from the CS/OJPs/CL nanoparticles were greatly affected by pH and enzymatic degradation (trypsin and lysozyme). The nanoparticles were easily internalized by macrophages, thereby enhancing the OJPs' inhibitory ability against Ni2+-induced cytotoxicity and LPS-induced nitric oxide production. This study demonstrates that prepared polysaccharide/protein co-assembled nanoparticles can be potential nanocarriers for the oral delivery of bioactive polysaccharides with anti-inflammatory functions.