Genetic mutation patterns among glioblastoma patients in the Taiwanese population - insights from a single institution retrospective study.

This study utilized Next-Generation Sequencing (NGS) to explore genetic determinants of survival duration in Glioblastoma Multiforme (GBM) patients. We categorized 30 primary GBM patients into two groups based on their survival periods: extended survival (over two years, N = 17) and abbreviated survival (under two years, N = 13). For identifying pathogenic or likely pathogenic variants, we leveraged the ClinVar database. The cohort, aged 23 to 66 (median: 53), included 17 patients in Group A (survival >2 years, 10 males, 7 females), and 13 patients in Group B (survival <2 years, 8 males, 5 females), with a 60% to 40% male-to-female ratio. Identified mutations included CHEK2 (c.1477 G > A, p.E493K), IDH1 (c.395 G > A, p.R132H), and TP53 mutations. Non-coding regions exhibited variants in the TERT promoter (c.-146C > T, c.-124C > T) and TP53 RNA splicing site (c.376-2 A > C, c.376-2 A > G). While Group A had more mutations, statistical significance wasn't reached, likely due to sample size. Notably, TP53, and ATR displayed a trend toward significance. Surprisingly, TP53 mutations were more prevalent in Group A, contradicting Western findings on poorer GBM prognosis. In Taiwanese GBM patients, bevacizumab usage is linked to improved survival rates, affirming its safety and effectiveness. EGFR mutations are infrequent, suggesting potential distinctions in carcinogenic pathways. Further research on EGFR mutations and amplifications is essential for refining therapeutic approaches. TP53 mutations are associated with enhanced survival, but their functional implications necessitate detailed exploration. This study pioneers genetic analysis in Taiwanese GBM patients using NGS, advancing our understanding of their genetic landscape.

Development of a rapid aptamer-chemiluminescence sensor for detecting glyphosate pesticide residue in soybeans.

Glyphosate (GLY) is a widely used herbicide worldwide, particularly in cultivating genetically modified soybeans resistant to GLY. However, routine multi-residue analysis does not include GLY due to the complexity of soybean matrix components that can interfere with the analysis. This study presented the development of an aptamer-based chemiluminescence (Apt-CL) sensor for rapidly screening GLY pesticide residue in soybeans. The GLY-binding aptamer (GBA) was developed to bind to GLY specifically, and the remaining unbound aptamers were adsorbed onto gold nanoparticles (AuNPs). The signal was in the form of luminol-H2O2 emission, catalyzed by the aggregation of AuNPs in a chemiluminescent reaction arising from the GLY-GBA complex. The outcomes demonstrated a robust linear relationship between the CL intensity of GLY-GBA and the GLY concentration. In the specificity test of the GBA, only GLY and Profenofos were distinguished among the fifteen tested pesticides. Furthermore, the Apt-CL sensor was conducted to determine GLY residue in organic soybeans immersed in GLY as a real sample, and an optimal linear concentration range for detection after extraction was found to be between 0.001 and 10 mg/L. The Apt-CL sensor exploits the feasibility of real-time pesticide screening in food safety.

A Semi-Automatic Environmental Monitoring Device for Mercury and Cobalt Ion Detection.

A syringe-based, semi-automatic environmental monitoring device is developed for on-site detection of harmful heavy metal ions in water. This portable device consists of a spring-embedded syringe and a polydimethylsiloxane (PDMS) membrane-based flow regulator for semi-automatic fix-and-release fluidic valve actuation, and a paper-based analytical device (PAD) with two kinds of gold nanoclusters (AuNCs) for sensitive Hg2+ and Co2+ ion detection, respectively. The thickness of the elastic PDMS membrane can be adjusted to stabilize and modulate the flow rates generated by the pushing force provided by the spring attached to the plunger. Also, different spring constants can drastically alter the response time. People of all ages can extract the fix-volume sample solutions and then release them to automatically complete the detection process, ensuring high reliability and repeatability. The PAD comprises two layers of modified paper, and each layer is immobilized with bovine serum albumin-capped gold nanoclusters (R-AuNCs) and glutathione-capped gold clusters (G-AuNCs), respectively. The ligands functionalized on the surface of the AuNCs not only can fine-tune the optical properties of the nanoclusters but also enable specific and simultaneous detection of Hg2+ and Co2+ ions via metallophilic Au+ -Hg2+ interaction and the Co2+ -thiol complexation effect, respectively. The feasibility of the device for detecting heavy metal ions at low concentrations in various environmental water samples is demonstrated. The Hg2+ and Co2+ ions can be seen simultaneously within 20 min with detection limits as low as 1.76 nm and 0.27 µm, respectively, lower than those of the regulatory restrictions on water by the US Environmental Protection Agency and the European Union. we expect this sensitive, selective, portable, and easy-to-use device to be valid for on-site multiple heavy metal ion pollution screenings in resource-constrained settings.

NIR-activated quercetin-based nanogels embedded with CuS nanoclusters for the treatment of drug-resistant biofilms and accelerated chronic wound healing.

We have developed multifunctional nanogels with antimicrobial, antioxidant, and anti-inflammatory properties, facilitating rapid wound healing. To prepare the multifunctional nanogels, we utilized quercetin (Qu) and a mild carbonization process to form carbonized nanogels (CNGs). These CNGs possess excellent antioxidative and bacterial targeting properties. Subsequently, we utilized the Qu-CNGs as templates to prepare nanogels incorporating copper sulfide (CuS) nanoclusters, further enhancing their functionality. Notably, the CuS/Qu-CNGs nanocomposites demonstrated an exceptional minimum inhibitory concentration against tested bacteria, approximately 125-fold lower than monomeric Qu or Qu-CNGs. This enhanced antimicrobial effect was achieved by leveraging near-infrared II (NIR-II) light irradiation. Additionally, the CuS/Qu-CNGs exhibited efficient penetration into the extracellular biofilm matrix, eradicating methicillin-resistant Staphylococcus aureus-associated biofilms in diabetic mice wounds. Furthermore, the nanocomposites were found to suppress proinflammatory cytokines, such as IL-1ß, at the wound sites while regulating the expression of anti-inflammatory factors, including IL-10 and TGF-ß1, throughout the recovery process. The presence of CuS/Qu-CNGs promoted angiogenesis, epithelialization, and collagen synthesis, thereby accelerating wound healing. Our developed CuS/Qu-CNGs nanocomposites have great potential in addressing the challenges associated with delayed wound healing caused by microbial pathogenesis.

The Impact of Monthly Prophylactic Antibiotics Use in Patients with Recurrent Cellulitis: A 20-Year Population-Based Cohort Study in a Medical Center.

Purpose: The vicious cycle of recurrent cellulitis ultimately results in a high risk of relapse, which facilitates the use of antibiotic prophylaxis with monthly intramuscular benzathine penicillin G (BPG) to prevent recurrence. However, several clinical situations hinder the guideline recommendations in daily practice. Therefore, intramuscular clindamycin has been used as an alternative in our institution for years. This study aims to elucidate the effectiveness of monthly intramuscular antibiotics in preventing further cellulitis recurrence and evaluate the applicability of intramuscular clindamycin as an alternative to BPG. Patients and Methods: A retrospective cohort study was conducted at a medical center in Taiwan from January 2000 to October 2020. Adult patients with recurrent cellulitis were enrolled to receive monthly intramuscular antibiotic prophylaxis (including 1.2-2.4MU BPG or 300-600mg intramuscular clindamycin) or to be observed without prophylaxis. The decision to administer prophylaxis or observe was made at the discretion of the examining infectious disease specialists. Cox proportional-hazards regressions were performed to estimate hazard ratios (HR) and adjust for variables between groups. The Kaplan-Meier method was used to estimate survival curves. Results: Enrollment in the study consisted of 426 patients, with 222 receiving BPG, 106 receiving intramuscular clindamycin, and 98 being observed without prophylaxis. Both types of antibiotics resulted in a significantly lower recurrence rate than observation alone (27.9% for BPG, 32.1% for intramuscular clindamycin, and 82.7% for observation, P < 0.001). After adjusting for multiple variables, antibiotic prophylaxis continued to significantly reduce the risk of cellulitis recurrence by 82% (HR 0.18, 95% CI 0.13 to 0.26), by 86% (HR 0.14, 95% CI 0.09 to 0.20) with BPG, and by 77% (HR 0.23, 95% CI 0.14 to 0.38) with intramuscular clindamycin. Conclusion: Monthly intramuscular antibiotic prophylaxis was demonstrated to be effective in reducing cellulitis recurrence. Moreover, in the real-world practice, intramuscular clindamycin may serve as a reasonable alternative option to BPG.

Effects of Sodium Dodecyl Sulfate on the Enzyme Catalysis and Conformation of a Recombinant γ-Glutamyltranspeptidase from Bacillus licheniformis.

The study of interactions between proteins and surfactants is of relevance in a diverse range of applications including food, enzymatic detergent formulation, and drug delivery. In spite of sodium dodecyl sulfate (SDS)-induced unfolding has been studied in detail at the protein level, deciphering the conformation-activity relationship of a recombinant γ-glutamyltranspeptidase (BlrGGT) from Bacillus licheniformis remains important to understand how the transpeptidase activity is related to its conformation. In this study, we examined the enzyme catalysis and conformational transition of BlrGGT in the presence of SDS. Enzymatic assays showed that the transpeptidase activity of BlrGGT was greatly affected by SDS in a concentration-dependent manner with approximately 90% inactivation at 6 mM. Native polyacrylamide gel electrophoresis of SDS-treated samples clearly revealed that the heterodimeric enzyme was apparently dissociated into two different subunits at concentrations above 2 mM. The study of enzyme kinetics showed that SDS can act as a mixed-type inhibitor to reduce the catalytic efficiency of BlrGGT. Moreover, the t1/2 value of the enzyme at 55 °C was greatly reduced from 495.1 min to 7.4 min in the presence of 1 mM SDS. The I3/I1 ratio of pyrene excimer fluorescence emission changed around 3.7 mM SDS in the absence of BlrGGT and the inflection point of enzyme samples was reduced to less than 2.7 mM. The Far-UV CD spectrum of the native enzyme had two negative peaks at 208 and 222 nm, respectively; however, both negative peaks increased in magnitude with increasing SDS concentration and reached maximal values at above 4.0 mM. The intrinsic fluorescence spectra of tryptophan further demonstrated that the SDS-induced enzyme conformational transition occurred at approximately 5.1 mM. Tween 20 significantly suppressed the interaction of BlrGGT with SDS by forming mixed micelles at a molar ratio of 1.0. Taken together, this study definitely promotes our better understanding of the relationship between the conformation and catalysis of BlrGGT.

Supramolecular hydrogel for programmable delivery of therapeutics to cancer multidrug resistance.

Multidrug resistance (MDR) has been considered as a major adversary in oncologic chemotherapy. To simultaneously overcome drug resistance and inhibit tumor growth, it is essential to develop a drug delivery system that can carry and release multiple therapeutic agents with spatiotemporal control. In this study, we developed a hydrogel containing an enzyme-cleavable peptide motif, with a network structure formed by 4-armed polyethylene glycol (PEG) crosslinked by complementary nucleic acid sequences. Hydrogen bond formation between nucleobase pairing allows the hydrogel to be injectable, and the peptide motif grants deliberate control over hydrogel degradation and the responsive drug release. Moreover, MDR-targeted siRNAs are complexed with stearyl-octaarginine (STR-R8), while doxorubicin (Dox) is intercalated with DNA and nanoclay structures in this hydrogel to enhance therapeutic efficacy and overcome MDR. The results show a successful configuration of a hydrogel network with in situ gelation property, injectability, and degradability in the presence of tumor-associated enzyme, MMP-2. The synergistic effect by combining MDR-targeted siRNAs and Dox manifests with the enhanced anti-cancer effect on drug resistant breast cancer cells in both in vitro and in vivo tumor models. We suggest that with the tailor-designed hydrogel system, multidrug resistance in tumor cells can be significantly inhibited by the co-delivery of multiple therapeutics with spatial-temporal control release.

Nanomedicines Targeting Glioma Stem Cells.

Glioblastoma (GBM), classified as a grade IV glioma, is a rapidly growing, aggressive, and most commonly occurring tumor of the central nervous system. Despite the therapeutic advances, it carries an ominous prognosis, with a median survival of 14.6 months after diagnosis. Accumulating evidence suggests that cancer stem cells in GBM, termed glioma stem cells (GSCs), play a crucial role in tumor propagation, treatment resistance, and tumor recurrence. GSCs, possessing the capacity for self-renewal and multilineage differentiation, are responsible for tumor growth and heterogeneity, leading to primary obstacles to current cancer therapy. In this respect, increasing efforts have been devoted to the development of anti-GSC strategies based on targeting GSC surface markers, blockage of essential signaling pathways of GSCs, and manipulating the tumor microenvironment (GSC niches). In this review, we will discuss the research knowledge regarding GSC-based therapy and the underlying mechanisms for the treatment of GBM. Given the rapid progression in nanotechnology, innovative nanomedicines developed for GSC targeting will also be highlighted from the perspective of rationale, advantages, and limitations. The goal of this review is to provide broader understanding and key considerations toward the future direction of GSC-based nanotheranostics to fight against GBM.

Photoswitchable carbon-dot liposomes mediate catalytic cascade reactions for amplified dynamic treatment of tumor cells.

Most biochemical reactions that occur in living organisms are catalyzed by a series of enzymes and proceed in a tightly controlled manner. The development of artificial enzyme cascades that resemble multienzyme complexes in nature is of current interest due to their potential in various applications. In this study, a nanozyme based on photoswitchable carbon-dot liposomes (CDsomes) was developed for use in programmable catalytic cascade reactions. These CDsomes prepared from triolein are amphiphilic and self-assemble into liposome-like structures in an aqueous environment. CDsomes feature excitation-dependent photoluminescence and, notably, can undergo reversible switching between a fluorescent on-state and nonfluorescent off-state under different wavelengths of light irradiation. This switching ability enables the CDsomes to exert photocatalytic oxidase- and peroxidase-like activities in their on- (bright) and off- (dark) states, respectively, resulting in the conversion of oxygen molecules into hydrogen peroxide (H2O2), followed by the generation of active hydroxyl radicals (OH). The two steps of oxygen activation can be precisely controlled in a sequential manner by photoirradiation at different wavelengths. Catalytic reversibility also enables the CDsomes to produce sufficient reactive oxygen species (ROS) to effectively kill tumor cells. Our results reveal that CDsomes is a promising photo-cycling nanozyme for precise tumor phototherapy through regulated programmable cascade reactions.

Novel application of a Co-Fermented postbiotics of TYCA06/AP-32/CP-9/collagen in the improvement of acne vulgaris-A randomized clinical study of efficacy evaluation.

BACKGROUND: Acne vulgaris is a chronic inflammatory skin disease. If skin lesions are not treated well in time, they can leave a permanent impact on the appearance and a negative influence on personal confidence. The common therapy for acne symptom includes antibiotics, benzoyl peroxide, and azeleic acid. However, those medications have side effects, and the long-term use should be cautious. Therefore, it is necessary to develop a safe and effective material, which is more suitable for daily use. OBJECTIVE: Collagen was selected to co-ferment with three probiotic strains TYCA06/AP-32/CP-9 (TAC) due to its excellent feature on wound healing. The fermented material was added into cosmetic gel and applied on subjects' acne lesions. The antimicrobial activity against Propionibacterium acnes and anti-inflammation effect around lesion area were investigated in a 4-week clinical study. MATERIAL AND METHODS: An anti-P. acnes assay, a keratinocytes HaCaT cell-based wound healing assay, and a cytokine assay on thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33 were used to evaluate the function of the fermented material in vitro. The TAC/Collagen formula was further incorporated into a cosmetic gel, and the human clinical trial was carried out by applying this gel on 20 volunteers' face with acne vulgaris. The moisture score, sebum content, inflammation, porphyrins numbers, and brown spot number of whole face were observed and recorded. RESULTS: The postbiotics of the TAC/Collagen displayed a good growth inhibition against P. acnes and reduced TSLP and IL-33 inflammation in vitro. This TAC/Collagen formula enhanced the wound healing in HaCaT cell culture. The result of the clinical trial showed the TAC/Collagen gel improved the moisture score and inflammation index of the skin in vivo. In addition, this TAC/Collagen gel also improved the wound healing of acne symptom in volunteers with acne vulgaris. Moreover, this TAC/Collagen gel reduced the number of the porphyrins and brown spots on facial skin. CONCLUSION: These postbiotics of TAC/Collagen have beneficial effects on skin health and are able to ameliorate the redness, inflammation, and acne symptom in acne vulgaris patients.

Self-redox reaction driven in situ formation of Cu2O/Ti3C2Tx nanosheets boost the photocatalytic eradication of multi-drug resistant bacteria from infected wound.

BACKGROUND: MXenes with interesting optical and electrical properties have been attractive in biomedical applications such as antibacterial and anticancer agents, but their low photogeneration efficiency of reactive oxygen species (ROS) and poor stability are major concerns against microbial resistance. METHODS: Water-dispersible single layer Ti3C2Tx-based MXene through etching tightly stacked MAX phase precursor using a minimally intensive layer delamination method. After addition of Cu(II) ions, the adsorbed Cu(II) ions underwent self-redox reactions with the surface oxygenated moieties of MXene, leading to in situ formation of Cu2O species to yield Cu2O/Ti3C2Tx nanosheets (heterostructures). RESULTS: Under NIR irradiation, the Cu2O enhanced generation of electron-hole pairs, which boosted the photocatalytic production of superoxide and subsequent transformation into hydrogen peroxide. Broad-spectrum antimicrobial performance of Cu2O/Ti3C2Tx nanosheets with sharp edges is attributed to the direct contact-induced membrane disruption, localized photothermal therapy, and in situ generated cytotoxic free radicals. The minimum inhibitory concentration of Cu2O/Ti3C2Tx nanosheets reduced at least tenfold upon NIR laser irradiation compared to pristine Cu2O/Ti3C2Tx nanosheets. The Cu2O/Ti3C2Tx nanosheets were topically administrated on the methicillin-resistant Staphylococcus aureus (MRSA) infected wounds on diabetic mice. CONCLUSION: Upon NIR illumination, Cu2O/Ti3C2Tx nanosheets eradicated MRSA and their associated biofilm to promote wound healing. The Cu2O/Ti3C2Tx nanosheets with superior catalytic and photothermal properties have a great scope as an effective antimicrobial modality for the treatment of infected wounds.

Evaluation of chemotherapeutic response in living cells using subcellular Organelle‒Selective amphipathic carbon dots.

Monitoring of structural changes in subcellular organelles is critical to evaluate the chemotherapeutic response of cells. However, commercial organelle selective fluorophores are easily photobleached, and thus are unsuitable for real-time and long-term observation. We have developed photostable carbon-dot liposomes (CDsomes)-based fluorophores for organellar and suborganellar imaging to circumvent these issues. The CDs synthesized through a mild pyrolysis/hydrolysis process exhibit amphipathic nature and underwent self-assembly to form liposome-like structures (CDsomes). The controlled hydrophilicity or hydrophobicity-guided preparation of CDsomes are used to selectively and rapidly (<1 min) stain nucleolus, cytoplasm, and membrane. In addition, the CDsomes offer universal high-contrast staining not only in fixed cells but also in living cells, allowing real-time observation and morphological identification in the specimen. The as-prepared CDsomes exhibit excitation-dependent fluorescence, and are much more stable under photoirradiation (e.g., ultraviolet light) than traditional subcellular dyes. Interestingly, the CDsomes can be transferred to daughter cells by diluting the particles, enabling multigenerational tracking of suborganelle for up to six generations, without interrupting the staining pattern. Therefore, we believe that the ultra-photostable CDsomes with high biocompatibility, and long-term suborganellar imaging capabilities, hold a great potential for screening and evaluating therapeutic performance of various chemotherapeutic drugs.

Adequacy of care during interfacility transfer in Taiwan: A pilot study.

BACKGROUND/PURPOSE: Interfacility transfer (IFT) in Asian communities is seldom discussed. We aimed to describe the characteristics of IFT in Taiwan and to explore the adequacy of care during transfer. METHODS: A retrospective, cross-sectional, descriptive study was conducted using standardized, paper-based interfacility ambulance transfer records between 1 January 2018 and 31 January 2018 from Tainan City, Taiwan. The mode of patient care needed was classified as advanced life support (ALS) or basic life support (BLS) cares based on clinical conditions. ALS providers were defined as physicians and EMT-Paramedics, while BLS providers were defined as nurse practitioners, nurses, EMT-1s and EMT-2s. RESULTS: Of the 377 (227 [60.2%] were >65 years old; 219 [58.1%] were male) IFTs enrolled in the final analysis, 210 (55.7%) patients met the ALS transfer criteria, with poor consciousness (n = 158), tachypnea (n = 17), tachycardia (n = 5), bradycardia (n = 7), hypertension (n = 12), hypotension (n = 13), hypoxia (n = 4), endotracheal intubation (n = 18), a tracheostomy (n = 25), a precipitous labor (n = 1), and after resuscitation for out-of-hospital cardiac arrest (n = 10) or in-hospital cardiac arrest (n = 3). None of the patients who required ALS care had adequate ambulance staffing. Of the 167 BLS IFTs, 9 (5.4%) patients deteriorated and required ALS care during transportation, which included worsened consciousness (n = 2), tachycardia (n = 1), hypertension (n = 2), hypotension (n = 1), and hypoxia (n = 3). The rates of deterioration during BLS-transferals from the emergency departments, general wards, nursing facilities, and unknown areas were 4.8%, 4.7%, 7.7%, and 7.1%, respectively (p = 0.93). CONCLUSION: The patient care during IFT in Taiwan is inadequate currently and should warrant attention.

Impact of the food grade heat-killed probiotic and postbiotic oral lozenges in oral hygiene.

The oral cavity plays a crucial role in food digestion and immune protection. Thus, maintaining oral health is necessary. Postbiotic and heat-killed probiotic cells have shown increased antibacterial potential with stable viability compared with live strains. However, clinical evidence regarding their effect on oral health is insufficient. Therefore, in this study, we tested postbiotic lozenges of Lactobacillus salivarius subsp. salicinius AP-32, L. paracasei ET-66, and L. plantarum LPL28 and heat-killed probiotic lozenges of L. salivarius subsp. salicinius AP-32 and L. paracasei ET-66 for their effect on oral health. In total, 75 healthy individuals were blindly and randomly divided into placebo, postbiotic lozenge, and heat-killed probiotic lozenge groups and were administered the respective lozenge type for 4 weeks. Postbiotic and heat-killed probiotic lozenge groups demonstrated antibacterial activities with a considerable increase in L. salivarius in their oral cavity. Furthermore, their salivary immunoglobulin A, Lactobacillus, and Bifidobacterium increased. Subjective questionnaires completed by the participants indicated that participants in both the experimental groups developed better oral health and intestinal conditions than those in the placebo group. Overall, our study revealed that a food additive in the form of an oral postbiotic or heat-killed probiotic lozenge may effectively enhance oral immunity, inhibit the growth of oral pathogens, and increase the numbers of beneficial oral microbiota.

Activation and thermal stabilization of a recombinant γ-glutamyltranspeptidase from Bacillus licheniformis ATCC 27811 by monovalent cations.

The regulation of enzyme activity through complexation with certain metal ions plays an important role in many biological processes. In addition to divalent metals, monovalent cations (MVCs) frequently function as promoters for efficient biocatalysis. Here, we examined the effect of MVCs on the enzymatic catalysis of a recombinant γ-glutamyltranspeptidase (BlrGGT) from Bacillus licheniformis ATCC 27,811 and the application of a metal-activated enzyme to L-theanine synthesis. The transpeptidase activity of BlrGGT was enhanced by Cs+ and Na+ over a broad range of concentrations with a maximum of 200 mM. The activation was essentially independent of the ionic radius, but K+ contributed the least to enhancing the catalytic efficiency. The secondary structure of BlrGGT remained mostly unchanged in the presence of different concentrations of MVCs, but there was a significant change in its tertiary structure under the same conditions. Compared with the control, the half-life (t1/2) of the Cs+-enriched enzyme at 60 and 65 °C was shown to increase from 16.3 and 4.0 min to 74.5 and 14.3 min, respectively. The simultaneous addition of Cs+ and Mg2+ ions exerted a synergistic effect on the activation of BlrGGT. This was adequately reflected by an improvement in the conversion of substrates to L-theanine by 3.3-15.1% upon the addition of 200 mM MgCl2 into a reaction mixture comprising the freshly desalted enzyme (25 µg/mL), 250 mM L-glutamine, 600 mM ethylamine, 200 mM each of the MVCs, and 50 mM borate buffer (pH 10.5). Taken together, our results provide interesting insights into the complexation of MVCs with BlrGGT and can therefore be potentially useful to the biocatalytic production of naturally occurring γ-glutamyl compounds. KEY POINTS: • The transpeptidase activity of B. licheniformis Î³-glutamyltranspeptidase can be activated by monovalent cations. • The thermal stability of the enzyme was profoundly increased in the presence of 200 mM Cs+. • The simultaneous addition of Cs+and Mg2+ions to the reaction mixture improves L-theanine production.

Predictive and prognostic factors for outcome of microvascular decompression in trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) is a disease characterized by recurring, short-lived, electric shock-like pain experienced on one side of the face. Microvascular decompression (MVD) is one of the most effective surgical interventions for resolving TN caused by neurovascular compression. This study aimed to determine the predictive and prognostic factors of surgical outcomes. METHODS: This retrospective cohort study enrolled patients diagnosed with TN who underwent MVD at our hospital during 2013-2019. The demographic information, pain character, peri-operative Barrow Neurological Institute (BNI) scale, medication, operative finding were recorded. And the outcome was Outcomes were divided into drug-free and drug-dependent group. Predisposing factors for each outcome were analyzed by one-way analysis of variance, followed by a Mann-Whitney U test or Kruskal-Wallis test. RESULTS: A total of 104 consecutive patients received MVD to treat TN, and 88 patients were enrolled in this study. The overall postoperative drug-free outcome was 72.7%. A significant difference in drug-free outcomes was observed for patients with typical TN (80.8%) compared with patients with atypical TN (33.33%, p = 0001). When severe venous compression was encountered during MVD, the drug-free outcome fell to 50% (10/20, p = 0.009). The Mann-Whitney U test indicated typical TN as a positive predictive factor of a drug-free outcome, whereas severe venous compression was a negative predictive factor. The patients with preoperative BNI score of 4 had better improvement than others (p = 0.045). Age, onset duration, and arterial loop had no specific difference in this study. CONCLUSION: In our study, atypical TN and severe venous compression were associated with poor outcomes. Regrouping atypical TN into precise diagnosis represents an immediate priority according to our result. The preoperative BNI score could be used as an effective predictive tool for the outcome of MVD surgery.

Self-assisted wound healing using piezoelectric and triboelectric nanogenerators.

The complex process of wound healing depends on the coordinated interaction between various immunological and biological systems, which can be aided by technology. This present review provides a broad overview of the medical applications of piezoelectric and triboelectric nanogenerators, focusing on their role in the development of wound healing technology. Based on the finding that the damaged epithelial layer of the wound generates an endogenous bioelectric field to regulate the wound healing process, development of technological device for providing an exogenous electric field has therefore been paid attention. Authors of this review focus on the design and application of piezoelectric and triboelectric materials to manufacture self-powered nanogenerators, and conclude with an outlook on the current challenges and future potential in meeting medical needs and commercialization.

Alleviation of dry eye syndrome with one dose of antioxidant, anti-inflammatory, and mucoadhesive lysine-carbonized nanogels.

Most dry eye syndromes (DES) are caused by oxidative stress and an overactive inflammatory response, leading to tear deficiency and excessive tear evaporation. Conventional eye drops for DES treatment require high doses and frequent administration due to their insufficient precorneal residence time. To overcome these problems, in this study, we have developed carbonized nanogels (CNGs) via the straightforward pyrolysis of lysine hydrochloride (Lys) to provide a long-lasting eye drop formulation for topical DES therapy. This methodology thermally converts Lys-into nitrogen-doped crosslinked polymers with embedded nanographitic structures, which enable efficient free radical scavenging. The cationic and crosslinked polymeric features of the Lys-CNGs also prolong the precorneal retention time and improve ocular bioavailability. These Lys-CNGs exhibit high biocompatibility with corneal epithelial cells both in vitro and in vivo, indicating their safety as eye drops. In a DES rabbit model, a single dose of Lys-CNGs (50 µg mL-1) can effectively alleviate the signs of DES within 4 days, whereas multiple treatments of 10-fold higher concentration of cyclosporine A are needed to achieve similar therapeutic effects (one dose every 12 h; 500 µg mL-1). The topical administration of Lys-CNGs enable a reduced therapeutic dose and extended dosing interval, thereby demonstrating a superior therapeutic efficacy compared to the commercial cyclosporine A eye drops. These Lys-CNGs, which exhibit significant free radical scavenging, anti-inflammatory activity, high biocompatibility, and a remarkable ocular bioadhesive property, hold great potential as a long-lasting eye drop formulation for the treatment of dry eye disease. STATEMENT OF SIGNIFICANCE: Multifunctional nanobiomaterial-based eye drops can render an ideal pharmaceutical formulation for the treatment of a variety of ocular surface diseases. To our knowledge, this is the first report describing the development of carbonized nanogels as topically administered therapeutics for alleviating dry eye syndrome (DES). We present evidence that the thermal transformation of lysine hydrochloride into carbonized nanogels (Lys-CNGs) endows superior antioxidant, anti-inflammatory, and bioadhesive properties. While a single dose of Lys-CNGs (50 µg mL-1) is sufficient to relieve the symptoms of DES for 4 days, multiple treatments of 10-fold higher concentration of commercially available cyclosporine eye drops are needed to achieve similar therapeutic outcomes (one dose every 12 h; 500 µg mL-1), suggesting an effective and long-lasting ocular carbonized nanomedicine.

Lozenges with probiotic strains enhance oral immune response and health.

OBJECTIVE: Probiotics participate in regulating oral microbiota and reducing the prevalence of oral diseases; however, clinical research on probiotics is insufficient. Therefore, in this study, we performed in vitro screening of potential oral protective probiotic strains and then evaluated the clinical efficacy of the selected strains on maintaining oral health. MATERIALS AND METHODS: Fifty healthy individuals were recruited and randomly assigned into the placebo group and probiotics group, which included three strains of probiotics, Lactobacillus salivarius subs. salicinius AP-32, Lactobacillus paracasei ET-66, and Lactobacillus plantarum LPL28. Each group was blindly administered placebo or probiotics for four weeks. RESULTS: Next-generation sequencing results showed that the oral microbiota of Lactobacillus salivarius in the oral cavity were significantly increased in subjects supplemented with mixed probiotic lozenges. The anti-bacterial activities of viable probiotics were observed within two weeks. Both IgA levels and Lactobacillus and Bifidobacterium abundances in the oral cavity were significantly increased in the experimental groups, along with a reduced formation of plaque. Most participants reported that their oral health conditions and intestinal symptoms had improved. CONCLUSIONS: Overall, our clinical study suggests that oral probiotic lozenges may enhance oral immunity, modulate oral microbiota, and improve oral health.

Catalytic and photoresponsive BiZ/CuxS heterojunctions with surface vacancies for the treatment of multidrug-resistant clinical biofilm-associated infections.

We report a one-pot facile synthesis of highly photoresponsive bovine serum albumin (BSA) templated bismuth-copper sulfide nanocomposites (BSA-BiZ/CuxS NCs, where BiZ represents in situ formed Bi2S3 and bismuth oxysulfides (BOS)). As-formed surface vacancies and BiZ/CuxS heterojunctions impart superior catalytic, photodynamic and photothermal properties. Upon near-infrared (NIR) irradiation, the BSA-BiZ/CuxS NCs exhibit broad-spectrum antibacterial activity, not only against standard multidrug-resistant (MDR) bacterial strains but also against clinically isolated MDR bacteria and their associated biofilms. The minimum inhibitory concentration of BSA-BiZ/CuxS NCs is 14-fold lower than that of BSA-CuxS NCs because their multiple heterojunctions and vacancies facilitated an amplified phototherapeutic response. As-prepared BSA-BiZ/CuxS NCs exhibited substantial biofilm inhibition (90%) and eradication (>75%) efficiency under NIR irradiation. Furthermore, MRSA-infected diabetic mice were immensely treated with BSA-BiZ/CuxS NCs coupled with NIR irradiation by destroying the mature biofilm on the wound site, which accelerated the wound healing process via collagen synthesis and epithelialization. We demonstrate that BSA-BiZ/CuxS NCs with superior antimicrobial activity and high biocompatibility hold great potential as an effective photosensitive agent for the treatment of biofilm-associated infections.