Volumetric compression by heterogeneous scaffold embedding promotes cerebral organoid maturation and does not impede growth.

Although biochemical regulation has been extensively studied in organoid modeling protocols, the role of mechanoregulation in directing stem cell fate and organoid development has been relatively unexplored. To accurately replicate the dynamic organoid development observed in nature, in this study, we present a method of heterogeneous embedding using an alginate-shell-Matrigel-core system. This approach allows for cell-Matrigel remodeling by the inner layer and provides short-term moderate-normal compression through the soft alginate outer layer. Our results show that the time-limited confinement contributes to increased expression of neuronal markers such as neurofilament (NF) and microtubule-associated protein 2 (MAP2). Compared with non-alginate embedding and alginate compression groups, volume growth remains unimpeded. Our findings demonstrate the temporary mechanical regulation of cerebral organoid growth, which exhibits a regular growth profile with enhanced maturation. These results highlight the importance and potential practical applications of mechanoregulation in the establishment of brain organoids. A record of this paper's transparent peer review process is included in the supplemental information.

Blue 405 nm LED light effectively inactivates bacterial pathogens on substrates and packaging materials used in food processing.

This study investigates the antimicrobial effectiveness of 405 nm light emitting diodes (LEDs) against pathogenic Escherichia coli O157:H7, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella Typhimurium, and Staphylococcus aureus, in thin liquid films (TLF) and on solid surfaces. Stainless steel (SS), high density polyethylene (HDPE), low density polyethylene (LDPE), and borosilicate glass were used as materials typically encountered in food processing, food service, and clinical environments. Anodic aluminum oxide (AAO) coupons with nanoscale topography were used, to evaluate the effect of topography on inactivation. The impact of surface roughness, hydrophobicity, and reflectivity on inactivation was assessed. A 48 h exposure to 405 nm led to reductions ranging from 1.3 (E. coli) to 5.7 (S. aureus) log CFU in TLF and 3.1 to 6.3 log CFU on different solid contact surfaces and packaging materials. All inactivation curves were nonlinear and followed Weibull kinetics, with better inactivation predictions on surfaces (0.89 ≤ R2 ≤ 1.0) compared to TLF (0.76 ≤ R2 ≤ 0.99). The fastest inactivation rate was observed on small nanopore AAO coupons inoculated with L. monocytogenes and S. aureus, indicating inactivation enhancing potential of these surfaces. These results demonstrate significant promise of 405 nm LEDs for antimicrobial applications in food processing and handling and the healthcare industry.

Causal association between vitamin D and diabetic neuropathy: a Mendelian randomization analysis.

OBJECTIVES: Vitamin D has been linked to diabetic neuropathy (DN) in previous epidemiological observational studies, however, their findings are inconsistent. The causal relationship between vitamin D and DN remains unknown. In this study we aim to investigate the causal association of serum 25-hydroxyvitamin D (25OHD) and DN. METHODS: Based on summary statistics from publicly available genome-wide association studies (GWAS) database, we detected the genetic correlation between serum 25OHD levels and DN by a two-sample Mendelian randomization (MR) analysis. The inverse-variance weighted (IVW) method was used as the primary analysis, weighted median and MR-Egger were applied as complementary methods for MR estimates. In addition, we took sensitivity analyses including Cochran's Q test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) and leave-one-out analysis to ensure that we obtained stable and reliable results. RESULTS: Our MR study showed no significant genetic association between serum 25OHD levels and DN (OR = 1.13, 95% CI = 0.81-1.57, P = 0.46). Furthermore, in the reverse direction analysis, we did not find a significant causal effect of DN and serum 25OHD levels (OR = 0.99, 95% CI = 0.98-1.00, P = 0.09). Results of MR-Egger, Weighted Median were consistent with those of the IVW method. The sensitivity analysis suggesting that no significant heterogeneity and genetic pleiotropy was observed. CONCLUSIONS: Our results provided no evidence to support the causal association of serum 25OHD levels with DN.

A search of only four key databases would identify most randomized controlled trials of acupuncture: A meta-epidemiological study.

Little research has been conducted to assess which specific databases should be searched when performing a systematic review (SR) on acupuncture. The current study aimed to identify key databases and the optimal database combination to retrieve randomized controlled trials (RCTs) on acupuncture for inclusion in SRs. A systematic search for SRs in the field of acupuncture was conducted in order to identify target databases and RCTs were extracted from the SRs that had searched all target databases. The proportions of SRs that had achieved 100%, 95%, or 90% recall of RCTs and the total recall of RCTs in various combinations of target databases were calculated. Sensitivity analysis was performed on those SRs that included 10 or more RCTs. CNKI, WanFang, VIP, PubMed, CENTRAL and Embase were regarded as target databases. A total of 4349 acupuncture RCTs were extracted from 286 SRs. Searching all six target databases retrieved 99.3% of all RCTs while 99.1% were recalled by searching the combination of CNKI, WanFang, PubMed and CENTRAL. There were no significant differences on total recall of RCTs (p = 0.549) or in the proportion of SRs with 90% recall of RCTs (97.2% vs. 97.6%; p = 0.794) between searching the above four and the full six target databases. Most results were similar in the sensitivity analysis. The combined retrieval power of CNKI, WanFang, PubMed and CENTRAL was considered an efficient choice to retrieve acupuncture RCTs included in SRs.

Agreement of Risk-of -Bias varied in systematic reviews on acupuncture and was associated with methodological quality.

OBJECTIVES: The objective of the study was to evaluate the consistency of risk of bias assessments for overlapping randomized controlled trials (RCTs) included in systematic reviews (SRs) on acupuncture. STUDY DESIGN AND SETTING: Databases were searched for acupuncture SRs. A weighted kappa (κ) statistic was calculated, and logistic regression was used to explore the factors of disagreements. RESULTS: We included 241 RCTs from 109 SRs on acupuncture. The percentage disagreements ranged from 25% to 44%, with moderate agreement for random sequence generation (κ = 0.57), allocation concealment (κ = 0.50), and incomplete outcome data (κ = 0.50), besides fair agreement for blinding of participants and personnel (κ = 0.44), blinding of outcome assessment (κ = 0.31), and selective reporting (κ = 0.39). Only 19% RCTs were evaluated completely consistent. Methodological quality (random sequence generation, odds ratio (OR) = 3.46), international cooperation (allocation concealment, OR = 0.14; incomplete outcome data, OR = 0.14; selective reporting, OR = 0.05), and risk of bias reporting completeness score (selective reporting, OR = 0.53) significantly affected the relative odds of disagreements. CONCLUSION: The level of agreement varied from fair to moderate agreement depending on the risk of bias domain. Methodological quality appears to be an overarching factor to account for disagreements.

Long-range interactions keep bacterial cells from liquid-solid interfaces: Evidence of a bacteria exclusion zone near Nafion surfaces and possible implications for bacterial attachment.

Hydrophilic surfaces of both abiotic and biological origin have been shown to bear particle-exclusion zones as large as hundreds of micrometers at liquid-solid interfaces. Here we present the first systematic investigation and evidence for bacteria-free exclusion zones for several bacterial strains, including pathogens associated with hospital infections and/or foodborne outbreaks: Staphylococcus aureus, Escherichia coli O157:H7, and Listeria monocytogenes. Tests were carried out both in a phosphate buffer, as well as triptic soy broth (TSB) of high ionic strength. Bacterial cell density distribution at the Nafion-liquid interface was visualized using confocal laser scanning microscopy. A robust image analysis method was developed to generate a profile of cell concentration near the interface and quantify EZ size. Results revealed an exclusion zone (EZ) of 40-60µm and a transition zone (TZ) of 40-80µm for bacterial cells suspended in tryptic soy broth. There were no statistical differences in the size of EZ and TZ for the bacterial strains tested with the same substrate, but differences existed for different substrates tested, implying a physicochemical underpinning for EZ. In a test conducted with E. coli, cells progressively penetrated EZ over 2days. Furthermore, EZ-bearing Nafion had 80% less biomass accumulation of E. coli over 2days compared to an EZ-less, hydrophilic, smooth aluminum oxide surface. This suggests that EZ may represent the first line of defense, spatially and temporally, against bacteria approaching certain hydrophilic surfaces. These findings could have important implications in developing biofouling-resistant material surfaces for applications sensitive to bacterial attachment and biofilm formation.

Alumina surfaces with nanoscale topography reduce attachment and biofilm formation by Escherichia coli and Listeria spp.

This work reports on a simple, robust and scientifically sound method to develop surfaces able to reduce microbial attachment and biofilm development, with possible applications in medicine, dentistry, food processing, or water treatment. Anodic surfaces with cylindrical nanopores 15 to 100 nm in diameter were manufactured and incubated with Escherichia coli ATCC 25922 and Listeria innocua. Surfaces with 15 and 25 nm pore diameters significantly repressed attachment and biofilm formation. Surface-bacteria interaction forces calculated using the extended Derjaguin Landau Verwey-Overbeek (XDLVO) theory indicate that reduction in attachment and biofilm formation is due to a synergy between electrostatic repulsion and surface effective free energy. An attachment study using E. coli K12 strains unable to express appendages also suggests that the small-pore surfaces may inhibit flagella-dependent attachment. These results can have immediate, far-reaching implications and commercial applications, with substantial benefits for human health and life.