Bio-Responsive Sliver Peroxide-Nanocarrier Serves as Broad-Spectrum Metallo-ß-lactamase Inhibitor for Combating Severe Pneumonia.

Metallo-ß-lactamases (MBLs) represent a prevalent resistance mechanism in Gram-negative bacteria, rendering last-line carbapenem-related antibiotics ineffective. Here, a bioresponsive sliver peroxide (Ag2 O2 )-based nanovesicle, named Ag2 O2 @BP-MT@MM, is developed as a broad-spectrum MBL inhibitor for combating MBL-producing bacterial pneumonia. Ag2 O2 nanoparticle is first orderly modified with bovine serum albumin and polydopamine to co-load meropenem (MER) and [5-(p-fluorophenyl)-2-ureido]-thiophene-3-carboxamide (TPCA-1) and then encapsulated with macrophage membrane (MM) aimed to target inflammatory lung tissue specifically. The resultant Ag2 O2 @BP-MT@MM effectively abrogates MBL activity by displacing the Zn2+ cofactor in MBLs with Ag+ and displays potent bactericidal and anti-inflammatory properties, specific targeting abilities, and great bioresponsive characteristics. After intravenous injection, the nanoparticles accumulate prominently at infection sites through MM-mediated targeting . Ag+ released from Ag2 O2 decomposition at the infection sites effectively inhibits MBL activity and overcomes the resistance of MBL-producing bacteria to MER, resulting in synergistic elimination of bacteria in conjunction with MER. In two murine infection models of NDM-1+ Klebsiella pneumoniae-induced severe pneumonia and NDM-1+ Escherichia coli-induced sepsis-related bacterial pneumonia, the nanoparticles significantly reduce bacterial loading, pro-inflammatory cytokine levels locally and systemically, and the recruitment and activation of neutrophils and macrophages. This innovative approach presents a promising new strategy for combating infections caused by MBL-producing carbapenem-resistant bacteria.

[Bioinformatics analysis of the RNA binding protein DDX39 of Toxoplasma gondii].

OBJECTIVE: To analyze the RNA binding protein of Toxoplasma gondii (TgDDX39) using bioinformatics technology, and to evaluate the immunogenicity of TgDDX39, so as to provide insights into development of toxoplasmosis vaccines. METHODS: The amino acid sequences of TgDDX39 were retrieved from the ToxoDB database, and the physicochemical properties, transmembrane structure domain, signal peptide sites, post-translational modification sites, coils, secondary and tertiary structures, hydrophobicity, and antigenic epitopes of the TgDDX39 protein were predicted using online bioinformatics tools, incluiding ProtParam, TMHMM 2.0, SignalP 5.0, NetPhos 3.1, COILS, SOPMA, Phyre2, ProtScale, ABCpred, SYFPEITHI and DNA-STAR. RESULTS: TgDDX39 protein was predicted to be an unstable hydrophilic protein with the molecular formula of C2173H3458N598O661S18, which contained 434 amino acids and had an estimated molecular weight of 49.1 kDa and a theoretical isoelectric point of 5.55. The protein was predicted to have an extremely low possibility of signal peptides, without transmembrane regions, and contain 27 phosphorylation sites. The ß turn and random coils accounted for 39.63% of the secondary structure of the TgDDX39 protein, and a coiled helix tended to produce in one site. In addition, the TgDDX39 protein contained multiple B and T cell antigenic epitopes. CONCLUSIONS: Bioinformatics analyses predict that TgDDX39 protein has high immunogenicity and contains multiple antigenic epitopes. TgDDX39 protein is a potential candidate antigen for vaccine development.

Predictive value of bone mineral density for postoperative efficacy and factors influencing treatment outcomes in patients undergoing total hip arthroplasty: a retrospective study.

OBJECTIVE: To investigate the value of bone mineral density (BMD) in predicting postoperative efficacy in patients undergoing total hip arthroplasty (THA), and to analyze the influencing factors of short-term outcomes. PATIENTS AND METHODS: Clinical data, including general data, perioperative indicators, and postoperative follow-up information, were collected from patients undergoing THA from July 2018 to June 2020 at Jiangsu Taizhou People's Hospital for retrospective analysis. Using the Harris Hip Score (HHS) at 12 months after THA as the therapeutic effect evaluation index, the BMD levels of patients with different therapeutic effects were compared, and the correlation of BMD with therapeutic efficacy was analyzed. Furthermore, the influencing factors of postoperative efficacy were discussed by using a logistic regression model. RESULTS: The HHS scores of 194 patients undergoing THA improved markedly at postoperative month 12 compared with the preoperative values (p<0.05), with a treatment excellent and good rate of 79.90% (155/194). The BMD level varied greatly among patients with different curative effects (p<0.05). Pearson correlation analysis identified a significant positive correlation between BMD values and HHS scores in patients undergoing THA. THA patients with different body mass index (BMI), surgical approach, occult blood loss, postoperative complications, length change of the affected limb, postoperative exercise time, and BMD had statistically significant differences in the excellent and good rate of clinical efficacy (p<0.05). According to the multivariate Logistic regression analysis, BMI, surgical approach, length change of the affected limb, and BMD were independent factors influencing the postoperative excellent and good rate of efficacy in THA patients (p<0.05). CONCLUSIONS: Preoperative BMD levels are strongly correlated with postoperative efficacy improvement in patients undergoing THA. BMD is an independent influencing factor of excellent and good postoperative efficacy in patients undergoing THA, and increasing the BMD is conducive to improving outcomes in such patients.

Bacterial Membrane Vesicles: Physiological Roles, Infection Immunology, and Applications.

Bacterial or fungal membrane vesicles, traditionally considered as microbial metabolic wastes, are secreted mainly from the outer membrane or cell membrane of microorganisms. However, recent studies have shown that these vesicles play essential roles in direct or indirect communications among microorganisms and between microorganisms and hosts. This review aims to provide an updated understanding of the physiological functions and emerging applications of bacterial membrane vesicles, with a focus on their biogenesis, mechanisms of adsorption and invasion into host cells, immune stimulatory effects, and roles in the much-concerned problem of bacterial resistance. Additionally, the potential applications of these vesicles as biomarkers, vaccine candidates, and drug delivery platforms are discussed.

Microneedle-Mediated Immunization Promotes Lung CD8+ T-Cell Immunity.

Microneedle array has proven more efficient in stimulating humoral immunity than intramuscular vaccination. However, its effectiveness in inducing pulmonary CD8+ T cells remains elusive, which is essential to the frontline defense against pulmonary viral infections such as influenza and COVID-19 viruses. The current investigation reveals that superior CD8+ T-cell responses are elicited by immunization with a microneedle array over intradermal or intramuscular immunization using the model antigen ovalbumin, irrespective of whether or not the antigen is provided in the lung. Mechanistically, microneedle array-mediated immunization targeted the epidermal layer and stimulated predominantly Langerhans cells, resulting in increased expression of α4ß1 adhesion molecules on the CD8+ T-cell surface, which may play a role in T-cell homing to the lung, whereas CD8+ T cells induced by intramuscular immunization did not express the adhesion molecule sufficiently. CD8+ T cells with a lung-homing propensity were also seen after intradermal vaccination, yet to a much lesser extent. Accordingly, microneedle array immunization provided stronger protection against influenza viral infection than intradermal or intramuscular immunization. The observations offer insights into a strong cross-talk between epidermal immunization and lung immunity and are valuable for designing and delivering vaccines against respiratory viral infections.

[Current status of lymph node dissection in pyloric-preserving gastrectomy for early gastric cancer].

With the gradual increase in the diagnosis rate of early gastric cancer, clinicians must consider prevention of gastric anatomical structure and physiological function while ensuring the radical treatment of the tumor. Pylorus-preserving gastrectomy is a function- preserving operation that preserves the pylorus, inferior pyloric vessel, and the vagus nerve in patients with early middle gastric cancer. One of the major controversies at present is the thoroughness of limited lymph node dissection for pyloric-preserving gastrectomy. Various studies have reported that the lymph node metastasis rate of early middle gastric cancer was low, especially in the suprapyloric region, inferior pylorus and the upper pancreatic region. Partial lymph node dissection is required for vascular and neurological protection, which is also safe and feasible in studies reported by major centers. Many clinical studies have been carried out in Japan and Korea, and postoperative follow-up has gradually increased evidence, providing the basis for the safety of lymph node dissection. In large case studies comparing pylorus- preserving gastrectomy with traditional distal gastrectomy, the incidence of postoperative morbidity, such as dumping syndrome, bile reflux esophagitis, weight loss, and malnutrition is low. Sentinel lymph node navigation technology is gradually applied to the diagnosis and treatment of early gastric cancer, and its clinical application value still needs further research.

[Clinical and endoscopic characteristics of adult celiac disease].

Objective: The study aimed to analyze the clinical and endoscopic characteristics of adult celiac disease (CD) to provide a scientific basis for more effective CD diagnosis and treatment. Methods: In this cross-sectional study, the clinical and endoscopic data of 96 adult CD patients treated in the Department of Gastroenterology of the People's Hospital of Xinjiang Uygur Autonomous Region from March 2016 to December 2021 were retrospectively collected and analyzed. Results: A total of 96 CD patients were diagnosed, including 33 men and 63 women. The average age was 47±14 years (range, 18-81 years). The disease occurred mainly in the age group of 31-60 years. The median course of the disease was 2.0 (0.2-40.0) years. There were 41 (42.7%) classical and 55 (57.3%) non-classical CD patients. All patients with classical CD showed chronic diarrhea, often accompanied by abdominal pain (46.3%, 19/41), abdominal distension (17.1%, 7/41), anemia (65.9%, 27/41), and chronic fatigue (48.8%, 20/41). The main manifestations of non-classical CD were chronic abdominal pain (58.2%, 32/55), abdominal distension (32.7%, 18/55), anemia (40.0%, 22/55), and osteopenia/osteoporosis (38.2%, 21/55). Compared with non-classical CD, anemia developed more frequently in classical CD, and the difference was statistically significant (P = 0.012). The incidence of complications in CD patients was 36.5% (35/96), and the main complications were thyroid disease (19.8%, 19/96), connective tissue disease (6.2%, 6/96), and kidney disease (6.2%, 6/96). There was no significant difference between classical and non-classical CD (P>0.05). The frequency of endoscopic manifestations in CD patients was 84.4% (81/96). Duodenal bulb endoscopy showed nodular changes (72.9%, 70/96), grooved changes (10.4%, 10/96), and focal villous atrophy (9.4%, 9/96). The main manifestations of descending endoscopy were the decrease, flattening, or disappearance of duodenal folds (43.8%, 42/96), scallop-like changes (38.5%, 37/96), and nodular changes (34.4%, 33/96). Conclusions: Adult CD patients are mostly female. CD occurred mainly in the age group of 31-60 years. The clinical manifestations were mainly those of non-classical CD. Some patients often had other autoimmune diseases. Patients with characteristic endoscopic manifestations should be warned about the possibility of developing CD. Clinicians should strengthen the understanding of CD and reduce the related rates of missed diagnosis.

Visualization and elimination of polymicrobial biofilms by a combination of ALA-carvacrol-blue light.

Chronic wound infections caused by multidrug-resistant (MDR) bacteria are one of the serious threats to public health due to limited therapeutic options and lengthy care. This investigation combines 5-aminolevulinic acid (ALA), blue light (BL), and phytochemical carvacrol, named ABC cocktail or trio-therapy, to efficiently eliminate wound-related MDR pathogens. Both planktonic cells and biofilms of blue light-refractory Escherichia (E.) coli and Klebsiella (K.) pneumoniae succumbed to the trio-therapy partly due to porphyrin accumulations following ALA incubation. ALA either alone or alongside carvacrol could vigorously trigger bursts of reactive oxygen species (ROS) upon blue light irradiation in K. pneumoniae, but not in mammalian cells. The robust antimicrobial activity was extended to polymicrobial biofilms composed of five MDR pathogens (Staphylococcus aureus, E. coli, K. pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) in vitro and in vivo. Strikingly, polymicrobial biofilm in mouse wounds became readily visible in the presence of ALA owing to the increasing generation of porphyrins that exhibited bright red fluorescence in response to blue light. Thus, ALA not only enhances killing efficacy, but also helps to pinpoint the infections for guiding debridement, precise phototherapy, and timely assessment of treatment effectiveness. Featuring a broadened antimicrobial spectrum and advantages of bacterial/biofilm imaging, the trio-therapy can be used either alone or adjunctive to other wound management modalities to effectively combat MDR bacteria in wounds.

[Study on the difference of curative effect of conventional mercury displacement treatment on mercury in brain and kidney].

Objective: To explore the expulsion effect of sodium dimercaptopropanesulfonate (DMPS) on mercury in different organs of mercury poisoning and the therapeutic effect of glutathione (GSH) combined with antioxidant therapy on mercury poisoning. Methods: In February 2019, 50 SPF male SD rats were randomly divided into 5 groups, 10 rats in each group: A (saline negative control group) , B (HgCL2 positive control group) , treatment group (C: intramuscular injection of DMPS 15 mg/kg treatment, D: intramuscular injection of DMPS30 mg/kg treatment, E: intramuscular injection of DMPS 15 mg/kg and intraperitoneal injection of GSH200 mg/kg treatment) . Rats in group B, C, D and E were subcutaneously injected with mercury chloride solution (1 mg/kg) to establish a rat model of subacute mercury poisoning kidney injury. Rats in group A were subcutaneously injected with normal saline. After the establishment of the model, rats in the treatment group were injected with DMPS and GSH. Rats in group A and group B were injected with normal saline. At 21 d (treatment 7 d) and 28 d (treatment 14 d) after exposure, urine and blood samples of 5 rats in each group were collected. Blood biochemistry, urine mercury, urine microalbumin and mercury content in renal cortex, cerebral cortex and cerebellum were detected. Results: After exposure to mercury, the contents of mercury in renal cortex, cerebrum and cerebellum of rats in group B, C, D and E increased, and urine microalbumin increased. Pathology showed renal tubular injury and renal interstitial inflammation. Compared with group B, urinary mercury and renal cortex mercury in group C, D and E decreased rapidly after DMPS treatment, and there was no significant decrease in mercury levels in cerebellum and cerebral cortex of rats, accompanied by transient increase in urinary albumin after DMPS treatment (P<0.05) ; the renal interstitial inflammation in group E was improved after GSH treatment. There was a positive correlation between urinary mercury and the contents of mercury in renal cortex, cerebral cortex and cerebellum (r=0.61, 0.47, 0.48, P<0.05) . Conclusion: DMPS mercury expulsion treatment can significantly reduce the level of metal mercury in the kidney, and there is no significant change in the level of metal mercury in the cortex and cerebellum.

Oregano Oil and Harmless Blue Light to Synergistically Inactivate Multidrug-Resistant Pseudomonas aeruginosa.

Blue light (BL) at 405 nm and oregano essential oil (OEO) have shown bactericidal activity by its own. Here, we demonstrated that the two synergistically killed multidrug-resistant (MDR) Pseudomonas aeruginosa (Pa). Pa ATCC19660 and HS0065 planktonic cells and mature biofilms were reduced by more than 7 log10 after treatment by BL combined with OEO, in sharp contrast to no significant bacterial reduction with the monotreatment. The duo also sufficiently eliminated acute or biofilm-associated infection of open burn wounds in murine without incurring any harmful events in the skin. The synergic bactericide was attributed mainly to the ability of OEO to magnify cytotoxic reactive oxygen species (ROS) production initiated by BL that excited endogenous tetrapyrrole macrocycles in bacteria while completely sparing the surrounding tissues from the phototoxic action. OEO ingredient analysis in combination with microbial assays identified carvacrol and its isomer thymol to be the major phytochemicals that cooperated with BL executing synergic killing. The finding argues persuasively for valuable references of carvacrol and thymol in assessing and standardizing the bactericidal potential of various OEO products.

High-throughput identification of autoantibodies that target the human exoproteome.

Autoantibodies that recognize extracellular proteins (the exoproteome) exert potent biological effects but are challenging to detect. Here, we developed rapid extracellular antigen profiling (REAP), a high-throughput technique for the comprehensive discovery of exoproteome-targeting autoantibodies. Patient samples are applied to a genetically barcoded yeast surface display library containing 2,688 human extracellular proteins. Antibody-coated yeast are isolated, and sequencing of barcodes is used to identify displayed antigens. To benchmark REAP's performance, we screened 77 patients with autoimmune polyglandular syndrome type 1 (APS-1). REAP sensitively and specifically detected both known and previously unidentified autoantibodies in APS-1. We further screened 106 patients with systemic lupus erythematosus (SLE) and identified numerous autoantibodies, several of which were associated with disease severity or specific clinical manifestations and exerted functional effects on cell signaling ex vivo. These findings demonstrate the utility of REAP to atlas the expansive landscape of exoproteome-targeting autoantibodies and their impacts on patient health outcomes.

Blue light potentiates safety and bactericidal activity of p-Toluquinone.

Fewer antibiotics are available for effective management of bacterial infections to date owing to increasing multiple-drug resistance (MDR). Here, we expand our early success in combination of 405 nm blue light irradiation with phenolic compounds to sufficiently kill blue light-refractory MDR Escherichia coli (E. coli). p-Toluquinone (p-TQ) alongside blue light inactivated 7.3 log10E. coli within 6 min, whereas either alone was totally ineffective. A similar killing efficacy was attained with four other pathogens commonly seen in hospital-acquired infections and Enterococcus faecalis (Ef) that don't produce porphyrins-like molecules. The combinatory therapy prevented recurrence of E. coli infection in skin scratch wounds of murine. The bactericidal activity was ascribed to reactive oxygen species (ROS) generation triggered by blue light-mediated excitation of p-TQ, which is less likely to induce resistance because of multi-targeted and non-specific nature of ROS. Remarkably, toxic p-TQ became harmless to mammalian cells after brief exposure to blue light while retaining its bactericidal activity. The opposite effect of blue light on p-TQ activity unravels a novel, simple strategy to detoxify p-TQ and its combination with blue light as a safe and efficacious bactericidal modality for managing MDR bacterial infections.

[Determination of platinum anticancer drugs in occupational settings by ICP-MS].

Objective: To establish an inductively coupled plasma mass spectrometry (ICP-MS) for platinum antineoplastic drugs in the environment. Methods: The platinum antineoplastic drugs in the environmental table were eluted by wiping and collecting pure water, and the supernatant was taken by centrifugation and inductively coupled plasma mass spectrometry for detection. Results: The concentration range of 0-8.0 µg/L was good, the correlation coefficient was 1.000, the detection limit was 0.0006 µg/L, the lower quantitative limit was 0.002 µg/L, the method precision was between 0.9%-1.3%, and the sample standard recovery rate was between 97.0%-98.5%. Conclusion: This method has low detection limit, high accuracy and precision, and simple sample pretreatment, which is suitable for the determination of platinum antineoplastic drugs in environmental tables.

Low-level light pre-conditioning promotes C2C12 myoblast differentiation under hypoxic conditions.

Exercise, especially anaerobic one, can gradually increase muscle mass over time as a result of adaptive responses of muscle cells to ensure metabolic homeostasis in the tissue. Low-level light therapy (LLLT) or photobiomodulation exhibits beneficial effects on promoting muscular functions, regeneration, and recovery from exhausting exercise, although the underlying cellular mechanisms remain poorly understood. We found that hypoxia, a condition following anaerobic exercise, significantly impeded myotube differentiation from myoblasts. However, this adverse effect was blunted greatly by pre-exposure of myoblast cells to a 980 nm laser at 0.1 J/cm2 , resulting in almost nearly normal myotube differentiation. LLL pre-treatment enhanced myotube formation by 80%, with a tubular diameter of 4.28 ± 0.11 µm on average, representative of a 53.4% increase over sham light treatment. The normalized myoblast differentiation concurred with 68% more mitochondrial mass and myogenin expression over controls. Moreover, LLL pre-treatment appeared to enhance glucose uptake, prevent energy metabolic switch from oxidative phosphorylation to glycolysis, and diminish lactate production under hypoxic conditions. The observation provides valuable guidance with respect to the timing of LLLT and its potential effects on muscle strengths in concert with anaerobic exercise.

Reversal of Polymicrobial Biofilm Tolerance to Ciprofloxacin by Blue Light plus Carvacrol.

Chronic wound infections are often caused by multi-species biofilms and these biofilm-embedded bacteria exhibit remarkable tolerance to existing antibiotics, which presents huge challenges to control such infections in the wounds. In this investigation, we established a polymicrobial biofilm composed of P. aeruginosa, S. aureus, K. pneumoniae, and A. baumannii. We tested a cocktail therapy comprising 405-nm blue light (BL), carvacrol (Ca), and antibiotics on the multispecies biofilm. Despite the fact that all strains used to form the biofilm were susceptible to ciprofloxacin (CIP) in planktonic cultures, the biofilm was found to withstand ciprofloxacin as well as BL-Ca dual treatment, mainly because K. pneumoniae outgrew and became dominant in the biofilm after each treatment. Strikingly, when ciprofloxacin was combined with BL-Ca, the multispecies biofilms succumbed substantially and were eradicated at an efficacy of 99.9%. Mechanistically, BL-Ca treatment increased membrane permeability and potentiated the anti-biofilm activity of ciprofloxacin, probably by facilitating ciprofloxacin's entrance of the bacteria, which is particularly significant for K. pneumoniae, a species that is refractory to either ciprofloxacin or BL-Ca dual treatment. The results suggest that bacterial membrane damage can be one of the pivotal strategies to subvert biofilm tolerance and combat the recalcitrant multispecies biofilms.

[Proximal incisal edge length and recent clinical observation of Siewert type â ¡ advanced esophagogastric junction adenocarcinoma].

Objective: To investigate the clinical effect of the radical resection with a proximal incisal edge length of 20-25 mm and 30-35 mm in Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma, to shorten the minimum safe distance of the proximal incisal edge to 20-25 mm. Methods: A retrospective cohort study method was used. The clinical data of 166 patients with Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma who underwent total gastrectomy from January 2017 to August 2020 in the Department of Gastrointestinal Surgery, Heji Hospital Affiliated to Changzhi Medical College were retrospectively collected. According to the proximal incisal edge length, the patients were divided into two groups: the proximal incisal edge length of 20-25 mm group (69 cases) and 30-35 mm group (97 cases). The perioperative conditions and the 6-month follow-up after the operation were compared between the two groups. Results: There was no statistically significant difference in baseline information between the patients in the two groups (P>0.05). The operations of both groups were completed. The intraoperative operation time of the proximal incisal edge length of 20-25 mm group was shorter than that in the proximal incisal edge length of 30-35 mm group ((172±24)and(206±27)min, P<0.001). There were no significant differences in the amount of intraoperative blood loss, the treatment of the diaphragm during the operation and the positive rate of intraoperative freezing of the upper incisal edge between the patients in the two groups (all P>0.05). And there was no significant differences in the first exhaust time, gastric tube removal time, first feeding time and hospital stay after the operation of the two groups (all P>0.05). There was no significant differences in the incidence of anastomotic leakage, anastomotic stenosis, reflux esophagitis and intestinal obstruction after the operation between the patients in the two groups (all P>0.05). And there was no anastomotic leakage case among the 69 cases in the proximal incisal edge length of 20-25 mm group. Postoperative pathological treatment showed no significant differences in the vascular tumor thrombus and nerve infiltration between the two groups (both P>0.05). During the 6-month follow-up, there was no death or tumor recurrence in the two groups, and there was no significant difference in body weight loss at 6 months after the operation between the two groups (P=0.178). Conclusion: When radical resection of Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma is performed, it is feasible to shorten the minimum safe distance of the proximal incisal edge to 20-25 mm under the premise of ensuring R0 resection. The operation time is shortened. Due to the shortening the incisal edge distance, the anastomotic tension is decreased, and the incidence of postoperative anastomotic leakage is also reduced.

Corrigendum: Bactericidal Property of Oregano Oil Against Multidrug-Resistant Clinical Isolates.

[This corrects the article DOI: 10.3389/fmicb.2018.02329.].

Childhood Bacille Calmette-Guerin Vaccination and Its Association With Less Severe COVID-19 Pneumonia.

INTRODUCTION: The potential for Bacille Calmette-Guerin vaccination to mitigate COVID-19 severity and perhaps infection susceptibility has been hypothesized, attracting global attention given its off-target benefits shown in several respiratory viral infections. METHODS: In this retrospective study, patients with laboratory-confirmed COVID-19 from Wuhan Pulmonary Hospital, China were categorized into Bacille Calmette-Guerin‒vaccinated and nonvaccinated groups. Clinical records, demography, laboratory results, and chest computed tomography scans were extracted from electronic medical records and compared between the 2 groups. RESULTS: No adverse events were observed, except for an increased frequency of chills in the Bacille Calmette-Guerin‒vaccinated group compared with that in the unvaccinated group (p=0.014). There were no significant differences in oxygen demand for breathing, computed tomography scans, treatments, or outcomes between the 2 groups. However, Bacille Calmette-Guerin‒vaccinated group had significantly less severe pneumonia (p=0.028) and milder deficiency in liver function, consistent with a lower death rate than in the unvaccinated group. CONCLUSIONS: Bacille Calmette-Guerin vaccination received in childhood is associated with less severe COVID-19 pneumonia and milder liver function deficiency in addition to a lower death rate in Bacille Calmette-Guerin‒vaccinated patients than in nonvaccinated individuals.

Thermosensitive and Conductive Hybrid Polymer for Real-Time Monitoring of Spheroid Growth and Drug Responses.

Three-dimensional (3D) cell culture based on polymer scaffold provides a promising tool to mimic a physiological microenvironment for drug testing; however, the next-generation cell activity monitoring technology for 3D cell culture is still challenging. Conventionally, drug efficacy evaluation and cell growth heavily rely on cell staining assays, using optical devices or flow cytometry. Here, we report a dual-function polymer scaffold (DFPS) composed of thermosensitive, silver flake- and gold nanoparticle-decorated polymers, enabling conductance change upon cell proliferation or death for in situ cell activity monitoring and drug screening. The cell activity can be quantitatively monitored via measuring the conductance change induced by polymeric network swelling or shrinkage. This novel dual-function system (1) provides a 3D microenvironment to enable the formation and growth of tumor spheroid in vitro and streamlines the harvesting of tumor spheroids through the thermosensitive scaffold and (2) offers a simple and direct quantitative method to monitor 3D cell culture in situ for drug responses. As a proof of concept, we demonstrated that a breast cancer stem cell line MDA-MB-436 was able to form cell spheroids in the scaffold, and the conductance change of the sensor exhibited a linear relationship with cell concentration. To examine its potential in drug screening, cancer spheroids in the cell sensor were treated with paclitaxel (PTX) and docetaxel (DTX), and predicted quantitative evaluation of the cytotoxic effect of drugs was established. Our results indicated that this cell sensing system may hold promising potential in expanding into an array device for high-throughput drug screening.

Innovative Systems to Deliver Allergen Powder for Epicutaneous Immunotherapy.

Allergy is a disorder owing to hyperimmune responses to a particular kind of substance like food and the disease remains a serious healthcare burden worldwide. This unpleasant and sometimes fatal allergic disease has been tackled vigorously by allergen-specific immunotherapy over a century, but the progress made so far is far from satisfactory for some allergies. Herein, we introduce innovative, allergen powder-based epicutaneous immunotherapies (EPIT), which could potentially serve to generate a new stream of technological possibilities that embrace the features of super safety and efficacious immunotherapy by manipulating the plasticity of the skin immune system via sufficient delivery of not only allergens but also tolerogenic adjuvants. We attempt to lay a framework to help understand immune physiology of the skin, epicutaneous delivery of powdered allergy, and potentials for tolerogenic adjuvants. Preclinical and clinical data are reviewed showing that deposition of allergen powder into an array of micropores in the epidermis can confer significant advantages over intradermal or subcutaneous injection of aqueous allergens or other epicutaneous delivery systems to induce immunological responses toward tolerance at little risk of anaphylaxis. Finally, the safety, cost-effectiveness, and acceptability of these novel EPITs are discussed, which offers the perspective of future immunotherapies with all desirable features.