Engineering Charge Density Waves by Stackingtronics in Tantalum Disulfide.

In the realm of condensed matter physics and materials science, charge density waves (CDWs) have emerged as a captivating way to modulate correlated electronic phases and electron oscillations in quantum materials. However, collectively and efficiently tuning CDW order is a formidable challenge. Herein, we introduced a novel way to modulate the CDW order in 1T-TaS2 via stacking engineering. By introducing shear strain during the electrochemical exfoliation, the thermodynamically stable AA-stacked TaS2 consecutively transform into metastable ABC stacking, resulting in unique 3a × 1a CDW order. By decoupling atom coordinates, we atomically deciphered the 3D subtle structural variations in trilayer samples. As suggested by density functional theory (DFT) calculations, the origin of CDWs is presumably due to collective excitations and charge modulation. Therefore, our works shed light on a new avenue to collectively modulate the CDW order via stackingtronics and unveiled novel mechanisms for triggering CDW formation via charge modulation.

Selective Formation of Homochiral Dimers by Intermolecular Charge Transfer on a hBN Nanomesh.

In this study, a comprehensive characterization was conducted on a chiral starburst molecule (C57H48N4, SBM) using scanning tunneling microscopy. When adsorbed onto the hBN/Rh(111) nanomesh, these molecules demonstrate homochiral recognition, leading to a selective formation of homochiral dimers. Further tip manipulation experiments reveal that the chiral dimers are stable and primarily controlled by strong intermolecular interactions. Density functional theory (DFT) calculations supported that the chiral recognition of SBM molecules is governed by the intermolecular charge transfer mechanism, different from the common steric hindrance effect. This study emphasizes the importance of intermolecular charge transfer interactions, offering valuable insights into the chiral recognition of a simple bimolecular system. These findings hold significance for the future advancement in chirality-based electronic sensors and pharmaceuticals, where the chirality of molecules can impact their properties.

Hypoxia-activated XBP1s recruits HDAC2-EZH2 to engage epigenetic suppression of ΔNp63α expression and promote breast cancer metastasis independent of HIF1α.

Hypoxia is a hallmark of cancer development. However, the molecular mechanisms by which hypoxia promotes tumor metastasis are not fully understood. In this study, we demonstrate that hypoxia promotes breast cancer metastasis through suppression of ΔNp63α in a HIF1α-independent manner. We show that hypoxia-activated XBP1s forms a stable repressor protein complex with HDAC2 and EZH2 to suppress ΔNp63α transcription. Notably, H3K27ac is predominantly occupied on the ΔNp63 promoter under normoxia, while H3K27me3 on the promoter under hypoxia. We show that XBP1s binds to the ΔNp63 promoter to recruit HDAC2 and EZH2 in facilitating the switch of H3K27ac to H3K27me3. Pharmacological inhibition or the knockdown of either HDAC2 or EZH2 leads to increased H3K27ac, accompanied by the reduced H3K27me3 and restoration of ΔNp63α expression suppressed by hypoxia, resulting in inhibition of cell migration. Furthermore, the pharmacological inhibition of IRE1α, but not HIF1α, upregulates ΔNp63α expression in vitro and inhibits tumor metastasis in vivo. Clinical analyses reveal that reduced p63 expression is correlated with the elevated expression of XBP1, HDAC2, or EZH2, and is associated with poor overall survival in human breast cancer patients. Together, these results indicate that hypoxia-activated XBP1s modulates the epigenetic program in suppression of ΔNp63α to promote breast cancer metastasis independent of HIF1α and provides a molecular basis for targeting the XBP1s/HDAC2/EZH2-ΔNp63α axis as a putative strategy in the treatment of breast cancer metastasis.

Understanding the impact of formulation design on microstructure and drug release from porous microparticle-based tretinoin topical gels.

For proportionally formulated intermediate strengths of a topical product, the relationship of drug release across multiple strengths of a given product is not always well understood. The current study aims to assess the proportionality of tretinoin release rates across multiple strengths of tretinoin topical gels when manufactured using two different methods to understand the impact of formulation design on drug product microstructure and tretinoin release rate. Two groups of tretinoin gels of 0.04 %, 0.06 %, 0.08 % and 0.1 % strengths were manufactured. Gels in Group I were prepared by incorporating 4-10 % g/g of 1 % w/w tretinoin-loaded microparticles into a gel base. Gels in Group II were manufactured using 10 % g/g of the microparticles that were loaded with increasing amounts (0.4-1 % w/w) of tretinoin. The two groups of gels were characterized by evaluating microstructure using a polarized microscope, rheology using an oscillatory rheometer, and drug release using Vison® Microette™ Hanson vertical diffusion cells. The microscopic images were used to discriminate between the two groups of gels based on the abundance of microparticles in the gel matrix observed in the images. This abundance increased across gels of Group I and was similar across gels of Group II. The rheology parameters, namely viscosity at a shear rate of 10 s-1, shear thinning rate, storage, and loss modulus, increased across gels of Group I, and were not significantly different across gels of Group II. The release rate of tretinoin from the drug products was proportional to the nominal strength of the drug product in both Group I and Group II, with a correlation coefficient of 0.95 in each case, although the absolute release rates differed. Overall, changing the formulation design of tretinoin topical gels containing porous microparticles may change the physicochemical and structural properties, as well as the drug release rate of the product. Further, keeping the formulation design consistent across all strengths of microparticle-based topical gels is important to achieve proportional release rates across multiple strengths of a given drug product.

FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.

Tumor metastasis is the major cause of breast cancer morbidity and mortality. It has been reported that the F-box protein FBXO3 functions as an E3 ubiquitin ligase in regulating various biological processes, including host autoimmune, antiviral innate immunity, and inflammatory response. However, the role of FBXO3 in tumor metastasis remains elusive. We have previously shown that ΔNp63α is a common inhibitory target in oncogene-induced cell motility and tumor metastasis. In this study, we show that FBXO3 plays a vital role in PI3K-mediated breast cancer metastasis independent of its E3 ligase activity and ΔNp63α in breast cancer cells and in mouse. FBXO3 can bind to and stabilize USP4, leading to Twist1 protein stabilization and increased breast cancer cell migration and tumor metastasis. Mechanistically, FBXO3 disrupts the interaction between USP4 and aspartyl aminopeptidase (DNPEP), thereby protecting USP4 from DNPEP-mediated degradation. Furthermore, p110αH1047R facilitates the phosphorylation and stabilization of FBXO3 in an ERK1-dependent manner. Knockdown of either FBXO3 or USP4 leads to significant inhibition of PI3K-induced breast cancer metastasis. Clinically, elevated expression of p110α/FBXO3/USP4/Twist1 is associated with poor overall survival (OS) and recurrence-free survival (RFS) of breast cancer patients. Taken together, this study reveals that the FBXO3-USP4-Twist1 axis is pivotal in PI3K-mediated breast tumor metastasis and that FBXO3/USP4 may be potential therapeutic targets for breast cancer treatment.

Structural Characterization and Immunomodulatory Activity of a Mannose-Rich Polysaccharide Isolated from Bifidobacterium breve H4-2.

In this study, a novel homogeneous mannose-rich polysaccharide named EPS-1 from the fermentation broth of Bifidobacterium breve H4-2 was isolated and purified by anion exchange column chromatography and gel column chromatography. The primary structure of EPS-1 was analyzed by high-performance liquid chromatography, Fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry, and nuclear magnetic resonance. The results indicated that EPS-1 had typical functional groups of polysaccharides. EPS-1 with an average molecular weight of 3.99 × 104 Da was mainly composed of mannose (89.65%) and glucose (5.84%). The backbone of EPS-1 was →2,6)-α-d-Manp-(1→2)-α-d-Manp-(1→2,6)-α-d-Manp-(1→2)-α-d-Manp-(1→2,6)-α-d-Manp-(1→6)-α-d-Glcp-(1→ simultaneously containing two kinds of branched chains (α-d-Manp-(1→3)-α-d-Manp-(1→ and α-d-Manp-(1→). Besides, EPS-1 had a triple-helical conformation and exhibited excellent thermal stability. Moreover, the immunomodulatory activity of EPS-1 was evaluated by RAW 264.7 cells. Results indicated that EPS-1 significantly enhanced the viability of RAW 264.7 cells. EPS-1 could also be recognized by toll-like receptor 4, thereby activating the nuclear factors-κB (NF-κB) signaling pathway, promoting phosphorylation of related nuclear transcription factors, improving cell phagocytic activity, and promoting the secretion of NO, IL-6, IL-1ß, and TNF-α. Thus, EPS-1 could activate the TLR4-NF-κB signaling pathway to emerge immunomodulatory activity on macrophages. The above results indicate that EPS-1 can serve as a potential immune-stimulating polysaccharide.

USP36 stabilizes nucleolar Snail1 to promote ribosome biogenesis and cancer cell survival upon ribotoxic stress.

Tumor growth requires elevated ribosome biogenesis. Targeting ribosomes is an important strategy for cancer therapy. The ribosome inhibitor, homoharringtonine (HHT), is used for the clinical treatment of leukemia, yet it is ineffective for the treatment of solid tumors, the reasons for which remain unclear. Here we show that Snail1, a key factor in the regulation of epithelial-to-mesenchymal transition, plays a pivotal role in cellular surveillance response upon ribotoxic stress. Mechanistically, ribotoxic stress activates the JNK-USP36 signaling to stabilize Snail1 in the nucleolus, which facilitates ribosome biogenesis and tumor cell survival. Furthermore, we show that HHT activates the JNK-USP36-Snail1 axis in solid tumor cells, but not in leukemia cells, resulting in solid tumor cell resistance to HHT. Importantly, a combination of HHT with the inhibition of the JNK-USP36-Snail1 axis synergistically inhibits solid tumor growth. Together, this study provides a rationale for targeting the JNK-USP36-Snail1 axis in ribosome inhibition-based solid tumor therapy.

A case-control evaluation of Spasm control and Tolerability of the Modified Atkins diet versus classic ketogenic diet in Chinese Children with infantile epileptic spasms syndrome.

OBJECTIVE: This study was conducted to compare the efficacy, tolerability and safety of the modified Atkins diet (MAD) and the classic ketogenic diet (KD) in Chinese children with infantile epileptic spasms syndrome. METHODS: We retrospectively recruited and analyzed 56 children with infantile epileptic spasms syndrome started on the MAD (n = 21) and classic KD (n = 35) at our institution from June 2016 to July 2022. RESULTS: The MAD group had exhibited comparable rates of spasm reduction (>50%) as the classic KD group at the time point of 3 months (66.7% for MAD, 75% for KD; p = 0.510), 6 months (75% for MAD, 82.6% for KD; p = 0.694), and 12 months (84.6% for MAD, 90.9% for KD; p = 1.000). The probability of patients remaining on the MAD was higher (p = 0.048) than those consuming the classic KD. By analyzing discontinuation reasons, we found that the MAD patients had a lower rate of poor compliance than the classic KD patients (p = 0.014). Response to the diet at 1 month and fewer anti-seizure medicines (ASMs) had tried before KD initiation were possible factors in regard to likelihood of spasm-free response to the diet therapy at 3 months (p = 0.001 and p = 0.014, respectively). CONCLUSIONS: The efficacy of spasm control was similar in the MAD, with better tolerability and higher compliance compared to the classic KD. Therefore, MAD could be the primary treatment for children in China with- infantile epileptic spasms syndrome. Additionally, an earlier beginning of the diet treatment may have significant advantages.

Identification of a de novo variant in the ASXL2 gene related to Shashi-Pena syndrome.

BACKGROUND: ASXL2 encodes proteins involved in epigenetic regulation and the assembly of transcription factors at specific genomic loci. Germline de novo truncating variants in ASXL2 have been implicated in Shashi-Pena syndrome, which results in features of developmental delay (DD), glabellar nevus flammeus, hypotonia, and cardiac disorders. However, the variants are rare, and the clinical spectrum may be incomplete. METHODS: The clinical data such as brain MRI were collect. The whole exome sequencing was performed for genetic etiology analysis. RESULTS: Here, we report a patient with DD, hypotonia, early atrial septal defect, and abnormal white matter signal. She presented with Shashi-Pena syndrome with a truncated variant in ASXL2 (NM_018263.6, c.2142_2152del, p.Ser714Argfs*5). She died of a digestive tract infection when she was 1 year and 6 months old. CONCLUSIONS: Our study further expanded the spectrum of phenotypes and genetic variations of the syndrome, and we believe that it is necessary to screen the ASXL2 gene in patients with DD and cardiac and bone disorders.

Alkyne Insertion Enabled Vinyl to Acyl 1,5-Palladium Migration: Rapid Access to Substituted 5-Membered-Dihydrobenzofurans and Indolines.

"Through space" palladium/hydrogen shift is an efficient strategy to achieve selective functionalization of a specific remote C-H bond. Compared with relatively extensive exploited 1,4-palladium migration process, the relevant 1,5-Pd/H shift was far less investigated. We herein report a novel 1,5-Pd/H shift pattern between a vinyl and an acyl group. Through the pattern, rapid access to 5-membered-dihydrobenzofuran and indoline derivatives has been achieved. Further studies have unveiled an unprecedented trifunctionalization (vinylation, alkynylation and amination) of a phenyl ring through 1,5-palladium migration relayed decarbonylative Catellani type reaction. A series of mechanistic investigations and DFT calculations have provided insights into the reaction pathway. Notably, it was unveiled that the 1,5-palladium migration in our case prefers a stepwise mechanism involving a PdIV intermediate.

HSF1 activates the FOXO3a-ΔNp63α-CDK4 axis to promote head and neck squamous cell carcinoma cell proliferation and tumour growth.

Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent cancers worldwide. Heat shock factor 1 (HSF1) is a conserved transcriptional factor that plays a critical role in maintaining cellular proteostasis. However, the role of HSF1 in HNSCC development remains largely unclear. Here, we report that HSF1 promotes forkhead box protein O3a (FOXO3a)-dependent transcription of ΔNp63α (p63 isoform in the p53 family; inhibits cell migration, invasion, and metastasis), which leads to upregulation of cyclin-dependent kinase 4 expression and HNSCC tumour growth. Ablation of HSF1 or treatment with KRIBB11, a specific pharmacological inhibitor of HSF1, significantly suppresses ΔNp63α expression and HNSCC tumour growth. Clinically, the expression of HSF1 is positively correlated with the expression of ΔNp63α in HNSCC tumours. Together, this study demonstrates that the HSF1-ΔNp63α pathway is critically important for HNSCC tumour growth.

Diagnosis of Neurological Infections in Pediatric Patients from Cell-Free DNA Specimens by Using Metagenomic Next-Generation Sequencing.

Central nervous system (CNS) infections can cause significant morbidity and mortality, especially in children. Rapid and accurate pathogenic detection in suspected CNS infections is essential for disease control at the early stage of infection. To evaluate the performance of metagenomic next-generation sequencing (mNGS) of cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) in pediatric patients, we retrospectively analyzed the efficiency of cfDNA mNGS in children with CNS infections (n = 257) or noninfectious neurological disorders (n = 81). The CSF samples of 124 random subjects were used to evaluate the accuracy between mNGS of cfDNA and whole-cell DNA (wcDNA). In total, cfDNA mNGS detected a wide range of microbes with a detection rate of 71.0%, and the sensitivity and total coincidence rate with clinical diagnosis reached 68.9% and 67.5%, respectively. Compared with wcDNA mNGS, cfDNA mNGS had a higher efficacy in detecting viruses (66 versus 13) and Mycobacterium (7 versus 1), with significantly higher reads per million. The dominant causative pathogens were bacteria and viruses in CNS infections, but these presented with different pathogen spectra in different age categories. The best timing for the mNGS test ranged from 1 to 6 days after the start of anti-infection therapy, and the earlier mNGS started, the better was identification of bacterial CNS infections. This study emphasized that cfDNA mNGS had overall superiority to conventional methods on causative pathogen detection in pediatric CNS infections, and it was even better than wcDNA mNGS. Furthermore, research needs to be better validated in large-scale clinical trials to improve the clinical applications of cfDNA mNGS. IMPORTANCE Our study emphasized that cfDNA mNGS had overall superiority to conventional methods on causative pathogen detection in CNS-infected children, and it was even better than wcDNA mNGS. cfDNA mNGS detected a wide range of pathogens with a high total coincidence rate (67.5%) against clinical diagnosis. The best timing for cfDNA mNGS detection ranged from 1 to 6 days, rather than 0 days, after the start of empirical anti-infection therapy. The earlier mNGS started, the better the identifications of bacterial CNS infections. To the best of our knowledge, this research is the first report evaluating the clinical utility of mNGS with different methods (cfDNA versus wcDNA) of extracting DNA from CSF specimens in diagnosing pediatric CNS infections. Meanwhile, this is the largest cohort study that has evaluated the performance of mNGS using cfDNA from CSF specimens in pediatric patients with CNS infections.

A Novel Data Augmentation Method Based on CoralGAN for Prediction of Part Surface Roughness.

Deep learning networks can be applied to the field of intelligent prediction of part surface roughness. However, the surface roughness samples of parts have the problems of high collection cost, unbalanced categories, and complicated data distribution, which inevitably limit the application of deep learning network models in the field of intelligent prediction of part surface roughness. To solve these problems, this article proposes a novel data augmentation method based on CoralGAN for prediction of part surface roughness, which introduces the domain adaptive method deep coral function to help optimize the network parameters of the generator of generative adversarial network (GAN). Specifically, the vibration signal collected during processing is converted into frequency spectrum data and input into CoralGAN. The training of the generator is guided by coral loss, that is, the distance between the covariances of the real samples and generated samples features, not just the statistical consistency of the traditional GAN. Experiments have been carried out on the three-axis vertical machining center. Research shows that the proposed method can improve the prediction accuracy of part surface roughness to 95.5%.

FBXL2 promotes E47 protein instability to inhibit breast cancer stemness and paclitaxel resistance.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a high risk of metastasis and recurrence. Although chemotherapy has greatly improved the clinical outcome of TNBC patients, acquired drug resistance remains a huge challenge for TNBC treatment. Breast cancer stem cells (BCSCs) play a critical role in breast cancer development, metastasis, recurrence, and chemotherapy resistance. Thus, it is of great importance to decipher the underlying molecular mechanism of BCSCs regulation for TNBC drug resistance. In this study, we demonstrate that the F-box protein FBXL2 is a critical negative regulator of BCSCs stemness and that downregulation of FBXL2 plays a causal role in TNBC drug resistance. We show that expression levels of FBXL2 significantly influence CD44high/CD24low subpopulation and the mammosphere formation ability of TNBC cells. Ectopic expression of FBXL2 inhibits initiation of TNBC and overcomes paclitaxel resistance in vivo. In addition, activation of FBXL2 by nebivolol, a clinically used small-molecule inhibitor of the beta-1 receptor, markedly overcomes BCSCs-induced paclitaxel resistance. Mechanistically, we show that FBXL2 targets transcriptional factor E47 for polyubiquitin- and proteasome-mediated degradation, resulting in inhibition of BCSC stemness. Clinical analyses indicate that low expression of FBXL2 correlates with high expression of E47 as well as with high stemness features, and is associated with poor clinical outcomes of breast cancer patients. Taken together, these results highlight that the FBXL2-E47 axis plays a critical role in the regulation of BCSC stemness and paclitaxel resistance. Thus, targeting FBXL2 might be a potential therapeutic strategy for drug-resistant TNBC.

Effects of reduced chemical application by mechanical-chemical synergistic weeding on maize growth and yield in East China.

There is growing concern about the environmental impact of chemicals and the long-term effects of mechanical weeding, which inhibits weed regrowth. Mechanical-chemical synergy has become an alternative weeding practice. In this paper, the effects of reduced chemical application by mechanical-chemical synergetic weeding on maize growth and yield are studied via synergistic weeding experiments. Experiments were carried out using three chemical reduction ratios (25%, 50%, and 75%) and two chemical applications (full width and only seeding row). The existing inter- and intra-implements were integrated as weeding machinery for full range mechanical weeding. Two indicators (leaf area and dry matter weight) were defined as growth characteristics at the filling and maturity stages. The results show that the leaf area of mechanical-chemical synergistic treatments was larger than those of single mechanical or chemical weeding treatments at the filling stage, but there was no significant difference between the leaf area values of the synergetic treatments (P=0.939). At the filling and maturity stages, the dry matter weight of mechanical-chemical weeding treatments was greater compared to the chemical weeding treatment. At the filling stage, the dry matter weight of the mechanical-chemical synergistic weeding treatments was less than that of the mechanical weeding treatment. In contrast, at the maturity stage, the dry matter weight of mechanical-chemical weeding treatments was greater, indicating that the promotional effect of the mechanical-chemical synergistic model was more pronounced at the later stage of crop growth. Single weeding or non-weeding treatment significantly affected the number of grains per ear (p=0.037) and 1000 grain weight (p=0.019), but it has been observed to have no significant effect on yield (p=0.504). The number of grains per ear, 1000 grain weight, and yield of the mechanical-chemical synergistic treatment were observed to be better than those of the chemical treatment. When compared with the full range of mechanical weeding treatments, only synergistic treatment produced a higher yield. From the perspectives of leaf area and dry matter, yield and its components, at the filling and maturity stage, the effect of mechanical-chemical synergy with 50% chemical reduction is the best recommendation as it reduces the dosage of chemical application, without significantly affecting crop growth and yield.

Psychological outcomes and associated factors amongst healthcare workers during a single wave, deeper into the COVID-19 pandemic in China.

Background: To date, the repeated breakout of the novel coronavirus disease 2019 (COVID-19) pandemic across many regions in China has caused continuous physical and mental harm to health care workers. This study investigates the psychological burden of the pandemic and its associated risk factors among Chinese healthcare workers (HCWs) during a single wave of COVID-19. Methods: For this cross-sectional web-based survey conducted from January 16, 2022 to February 5, 2022, a total of 412 HCWs from Northwestern China were recruited. Their socio-demographic data and COVID-19 related survey variables were then collected using online self-rating questionnaires. In addition, the Chinese versions of well-validated instruments, including the 12-item General Health Questionnaire for psychiatric morbidity, the Generalized Anxiety Disorder Scale-7 for anxiety, the Patient Health Questionnaire-9 for depression and the Insomnia Severity Index-7 for insomnia, were used to assess the participants' mental health status. Multivariate logistic regression analysis was eventually performed to identify the risk factors associated with the psychological outcomes. Results: Of the 388 participants who were included in the final study (94.17% response rate), the prevalence of anxiety, depression, and insomnia symptoms were 25.3% (95% CI: 20.9-29.6%), 40.7% (95% CI: 35.8-45.6%), and 30.9% (95% CI: 26.3-35.5%), respectively. Multivariate logistic regression analysis revealed that being a woman and having a perceived need for psychological support were risk factors for all psychological outcomes, while poor disease cognition and perceived susceptibility were risk factors for anxiety. Poor disease cognition and being unvaccinated against COVID-19 were risk factors for depression, with the latter also being an independent risk factor for insomnia. Conclusion: This study has identified a relatively lower prevalence rate of psychological disorders among Chinese HCWs during a single wave, deeper into the COVID-19 pandemic. Female HCWs, and those who had a perceived need for psychological support, had poor disease cognition, were perceived as susceptible to COVID-19 and had not been vaccinated against COVID-19 deserve more attention.

Bifidobacterium breve Alleviates DSS-Induced Colitis in Mice by Maintaining the Mucosal and Epithelial Barriers and Modulating Gut Microbes.

This study was designed to explore the different intestinal barrier repair mechanisms of Bifidobacterium breve (B. breve) H4-2 and H9-3 with different exopolysaccharide (EPS) production in mice with colitis. The lipopolysaccharide (LPS)-induced IEC-6 cell inflammation model and dextran sulphate sodium (DSS)-induced mice colitis model were used. Histopathological changes, epithelial barrier integrity, short-chain fatty acid (SCFA) content, cytokine levels, NF-κB expression level, and intestinal flora were analyzed to evaluate the role of B. breve in alleviating colitis. Cell experiments indicated that both B. breve strains could regulate cytokine levels. In vivo experiments confirmed that oral administration of B. breve H4-2 and B. breve H9-3 significantly increased the expression of mucin, occludin, claudin-1, ZO-1, decreased the levels of IL-6, TNF-α, IL-1ß and increased IL-10. Both strains of B. breve also inhibited the expression of the NF-κB signaling pathway. Moreover, B. breve H4-2 and H9-3 intervention significantly increased the levels of SCFAs, reduced the abundance of Proteobacteria and Bacteroidea, and increased the abundance of Muribaculaceae. These results demonstrate that EPS-producing B. breve strains H4-2 and H9-3 can regulate the physical, immune, and microbial barrier to repair the intestinal damage caused by DSS in mice. Of the two strains, H4-2 had a higher EPS output and was more effective at repair than H9-3. These results will provide insights useful for clinical applications and the development of probiotic products for the treatment of colitis.

Physicochemical and structural evaluation of microparticles in tretinoin topical gels.

Drug release from microparticle-based topical gels may affect their bioavailability, safety and efficacy. This work sought to elucidate spatial distribution of the drug within the microparticle matrix and how this impacts the product's critical performance attributes. The purpose of this research was to inform the development of in vitro characterization approaches to support a demonstration of bioequivalence. Drug-free microparticles were loaded with tretinoin or drug-loaded microparticles were separated from purchased Retin-A Micro® (tretinoin) topical gel drug products. The resultant microparticles were analyzed for tretinoin content, drug loading efficiency, morphology, surface topography, surface pore size distribution, particle size distribution and tretinoin release. The solid-state characteristics and chemical interaction of tretinoin with the microparticles were also investigated. Microparticles loaded with tretinoin made in-house and those separated from Retin-A Micro® (tretinoin) topical gel were spherical, polydisperse and free of aggregates. The surface porosity of the microparticles was ∼19.8% with an average pore size of ∼327 nm. Microparticles loaded with tretinoin in-house were smaller in size and exhibited faster drug release than those separated from Retin-A Micro® (tretinoin) topical gel. Tretinoin release was found to increase with an increase in the drug loading. Based on XRD and DSC data, tretinoin was present in an amorphous state. The FTIR spectra indicated a disappearance of carbonyl band of microparticles and shifting of the hydroxyl band of tretinoin due to hydrogen bonding. The extent of drug loading and the solid-state interaction of tretinoin with the microparticles may be critical for drug release. Additional characterization of the drug products is necessary to understand the effect of the factors examined in this work on the bioavailability and efficacy of tretinoin gels.