Anti-oxidative mesoporous polydopamine-based hypotensive nano-eyedrop for improved glaucoma management.

Conventional hypotensive eye drops remain suboptimal for glaucoma management, primarily due to their limited intraocular bioavailability and the growing concern regarding ocular surface side effects. Therefore, there is an urgent need to develop innovative intraocular pressure (IOP)-lowering formulations that not only possess enhanced corneal penetration ability but also provide ocular surface protection. Herein, anti-oxidative mesoporous polydopamine nanoparticles (MPDA NPs) were explored as a nano-carrier for Brimonidine to address the above issues. Nearly monodisperse MPDA NPs with obvious nanopores were successfully prepared by template-removal method and used for encapsulation of Brimonidine benefiting from their high specific surface area. Interestingly, the PEGylated and drug loaded MPDA-PEG@Brim NPs showed a near neutral surface charge, which is expected to enhance intraocular drug delivery. Consequently, much higher concentration of Brimonidine in the aqueous humor was found after topical administration of MPDA-PEG@Brim nano-dispersion as compared to free Brimonidine solution. Accordingly, superior IOP reduction effect was achieved for the nano-formulation in both hypertensive and normotensive rat eyes. Moreover, MPDA-PEG NPs showed good capability in scavenging diverse free radicals, alleviating intracellular oxidative stress, and mitigating ocular surface oxidative level in a mouse model of preservative-induced dry eye. In addition, the excellent biosafety of this novel Brimonidine nanodrug was confirmed both in vitro and in vivo. Therefore, the present work may shed light on the development of next generation hypotensive formulations for extended ocular surface protection and glaucoma management.

Efficacy evaluation of a bivalent subunit vaccine against epidemic PEDV heterologous strains with low cross-protection.

Variant Porcine epidemic diarrhea virus (PEDV), which causes diarrhea and high mortality in piglets, has become a major pathogen, and co-epidemics of different subtypes of the virus have become a very thorny problem for the clinical prevention and control of PEDV. However, cross-protection between epidemic G2a and G2b subtype strains has not been observed, and there is currently no vaccine against both G2a and G2b strains. In this study, we demonstrate the low cross-protection between G2a and G2b strains with piglet immunization and challenge tests. The trimeric full-length S proteins of G2a and G2b variants were purified and a bivalent subunit vaccine against PEDV G2a/G2b-S was developed. In active and passive immune protection tests, the bivalent subunit vaccine produced high neutralizing antibody titers and S-specific immunoglobulin G (IgG) and IgA titers against both the G2a and G2b strains in piglets and sows. In the attack phase of the viruses, the clinical symptoms and microscopic lesions in the immunized groups were significantly alleviated. Importantly, the PEDV G2a/G2b-S bivalent subunit vaccine conferred effective passive immunity against PEDV G2a and G2b challenges in the form of colostrum-derived antibodies from the immunized sows. In conclusion, our data demonstrate the low cross-protection of PEDV epidemic G2a and G2b strains and show that the G2a/G2b-S bivalent subunit vaccine is protective against both G2a and G2b strains. It is therefore a candidate vaccine for PEDV prevention. IMPORTANCE: The detection rate of PEDV G2a subtype strains is currently increasing. Although commercial vaccines are available, most vaccines do not exert an ideal protective effect against these strains. Furthermore, there is no definitive research into the cross-protection between G2a and G2b strains, and no bivalent vaccine provides joint protection against both. Therefore, in this study, we investigated the cross-protection between PEDV G2a and G2b strains and designed a candidate bivalent subunit vaccine combining the trimeric S proteins of the G2a and G2b subtypes. We demonstrate that the cross-protection between strains G2a and G2b is poor and that this bivalent subunit vaccine protects piglets from viral attack by inducing both active and passive immunity. This study emphasizes the effectiveness of the PEDV G2a/G2b-S bivalent subunit vaccine and provides a feasible method for the development of efficient PEDV vaccines.

Genetic characterization and phylogenetic analysis of the S genes of porcine epidemic diarrhea virus isolates from China from 2020 to 2023.

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that has been the main cause of diarrhea in piglets since 2010 in China. The aim of this study was to investigate sequence variation and recombination events in the spike (S) gene of PEDV isolates from China. Thirty complete S gene sequences were obtained from PEDV-positive samples collected in six provinces in China from 2020 to 2023. Phylogenetic analysis showed that 10% (3/30) belonged to subtype GII-a, 6.67% (2/30) were categorized as subtype GII-b, 66.67% (20/30) were categorized as subtype GII-c, and 16.66% (5/30) were clustered with the S-INDEL strains. Amino acid sequence alignments showed that, when compared to strains of other subtypes, the GII-c strains had two characteristic amino acid substitutions (N139D and I289M). Five S-INDEL subtype strains had a single amino acid deletion (139N) and four amino acid substitutions (N118G, T137S, A138S, and D141G). Recombination analysis allowed six putative recombination events to be identified, one involving recombination between GII-c strains, two involving GII-c and GII-b strains, two involving GII-c and GI-a strains, and one involving GII-a and GI-b strains. These results suggest that recombination between PEDV strains has been common and complex in recent years and is one of the main reasons for the continuous variation of PEDV strains.

The role of immunoglobulin transport receptor, neonatal Fc receptor in mucosal infection and immunity and therapeutic intervention.

The neonatal Fc receptor (FcRn) can transport IgG and antigen-antibody complexes participating in mucosal immune responses that protect the host from most pathogens' invasion via the respiratory, digestive, and urogenital tracts. FcRn expression can be triggered upon stimulation with pathogenic invasion on mucosal surfaces, which may significantly modulate the innate immune response of the host. As an immunoglobulin transport receptor, FcRn is implicated in the pathophysiology of immune-related diseases such as infection and autoimmune disorders. In this review, we thoroughly summarize the recent advancement of FcRn in mucosal immunity and its therapeutic strategy. This includes insights into its regulation mechanisms of FcRn expression influenced by pathogens, its emerging role in mucosal immunity and its potential probability as a therapeutic target in infection and autoimmune diseases.

The synergy of recombinant NSP4 and VP4 from porcine rotavirus elicited a strong mucosal response.

Porcine rotavirus (PoRV) is one of the main pathogens causing diarrhea in piglets, and multiple genotypes coexist. However, an effective vaccine is currently lacking. Here, the potential adjuvant of nonstructural protein 4 (NSP4) and highly immunogenic structural protein VP4 prompted us to construct recombinant NSP486-175aa (NSP4*) and VP426-476aa (VP4*) proteins, combine them as immunogens to evaluate their efficacy. Results indicated that NSP4* enhanced systemic and local mucosal responses induced by VP4*. The VP4*-IgG, VP4*-IgA in feces and IgA-secreting cells in intestines induced by the co-immunization were significantly higher than those induced by VP4* alone. Co-immunization of NSP4* and VP4* also induced strong cellular immunity with significantly increased IFN-λ than the single VP4*. Summarily, the NSP4* as a synergistical antigen exerted limited effects on the PoRV NAbs elevation, but conferred strong VP4*-specific mucosal and cellular efficacy, which lays the foundation for the development of a more effective porcine rotavirus subunit vaccine.

Role of pattern recognition receptors in the development of MASLD and potential therapeutic applications.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent liver diseases worldwide, and its occurrence is strongly associated with obesity, insulin resistance (IR), genetics, and metabolic stress. Ranging from simple fatty liver to metabolic dysfunction-associated steatohepatitis (MASH), even to severe complications such as liver fibrosis and advanced cirrhosis or hepatocellular carcinoma, the underlying mechanisms of MASLD progression are complex and involve multiple cellular mediators and related signaling pathways. Pattern recognition receptors (PRRs) from the innate immune system, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), RIG-like receptors (RLRs), and DNA receptors, have been demonstrated to potentially contribute to the pathogenesis for MASLD. Their signaling pathways can induce inflammation, mediate oxidative stress, and affect the gut microbiota balance, ultimately resulting in hepatic steatosis, inflammatory injury and fibrosis. Here we review the available literature regarding the involvement of PRR-associated signals in the pathogenic and clinical features of MASLD, in vitro and in animal models of MASLD. We also discuss the emerging targets from PRRs for drug developments that involved agent therapies intended to arrest or reverse disease progression, thus enabling the refinement of therapeutic targets that can accelerate drug development.

An update on the incidence, risk factors and mechanisms of rituximab-associated neutropenia.

With the increasing application of rituximab (RTB) in hematological diseases and autoimmune diseases (AIDs), we have gradually increased our awareness of the adverse reaction of rituximab-associated neutropenia (RAN), but little is known about its true incidence rate, susceptibility risk factors and exact pathogenesis. At present, research groups have conducted a large number of studies on different populations. The team found that age (> 60), advanced disease, systemic lupus erythematosus (SLE) and combined cyclophosphamide therapy were independent risk factors for RAN. However, its exact mechanism is not completely clear. Several hypotheses have been put forward to solve this question, including the production of anti-neutrophil antibodies after RTB, the generation disorder and neutrophil maturation stagnation caused by abnormal B-cell reconstruction, and the amplification of T-large granular lymphocyte population that may induce neutrophil apoptosis. However, there are still many unsolved problems in all aspects of RAN. This article is an update of the incidence rate, risk factors and mechanisms of RAN.

Recombinant bivalent subunit vaccine combining truncated VP4 from P[7] and P[23] induces protective immunity against prevalent porcine rotaviruses.

Porcine rotaviruses (PoRVs) cause severe economic losses in the swine industry. P[7] and P[23] are the predominant genotypes circulating on farms, but no vaccine is yet available. Here, we developed a bivalent subunit PoRV vaccine using truncated versions (VP4*) of the VP4 proteins from P[7] and P[23]. The vaccination of mice with the bivalent subunit vaccine elicited more robust neutralizing antibodies (NAbs) and cellular immune responses than its components, even at high doses. The bivalent subunit vaccine and inactivated bivalent vaccine prepared from strains PoRVs G9P[7] and G9P[23] were used to examine their protective efficacy in sows and suckling piglets after passive immunization. The immunized sows showed significantly elevated NAbs in the serum and colostrum, and the suckling piglets acquired high levels of sIgA antibodies from the colostrum. Challenging subunit-vaccinated or inactivated-vaccinated piglets with homologous virulent strains did not induce diarrhea, except in one or two piglets, which had mild diarrhea. Immunization with the bivalent subunit vaccine and inactivated vaccine also alleviated the microscopic lesions in the intestinal tissues caused by the challenge with the corresponding homologous virulent strain. However, all the piglets in the challenged group displayed mild to watery diarrhea and high levels of viral shedding, whereas the feces and intestines of the piglets in the bivalent subunit vaccine and inactivated vaccine groups had lower viral loads. In summary, our data show for the first time that a bivalent subunit vaccine combining VP4*P[7] and VP4*P[23] effectively protects piglets against the diarrhea caused by homologous virulent strains.IMPORTANCEPoRVs are the main causes of diarrhea in piglets worldwide. The multisegmented genome of PoRVs allows the reassortment of VP4 and VP7 genes from different RV species and strains. The P[7] and P[23] are the predominant genotypes circulating in pig farms, but no vaccine is available at present in China. Subunit vaccines, as nonreplicating vaccines, are an option to cope with variable genotypes. Here, we have developed a bivalent subunit candidate vaccine based on a truncated VP4 protein, which induced robust humoral and cellular immune responses and protected piglets against challenge with homologous PoRV. It also appears to be safe. These data show that the truncated VP4-protein-based subunit vaccine is a promising candidate for the prevention of PoRV diarrhea.

Electrophysiological and morphological properties of prefrontal pyramidal neurons innervated by mediodorsal thalamus.

The high-order cognitive and executive functions are necessary for an individual to survive. The densely bidirectional innervations between the medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) play a vital role in regulating high-order functions. Pyramidal neurons in mPFC have been classified into several subclasses according to their morphological and electrophysiological properties, but the properties of the input-specific pyramidal neurons in mPFC remain poorly understood. The present study aimed to profile the morphological and electrophysiological properties of mPFC pyramidal neurons innervated by MD. In the past, the studies for characterizing the morphological and electrophysiological properties of neurons mainly relied on the electrophysiological recording of a large number of neurons and their morphologic reconstructions. But, it is a low efficient method for characterizing the circuit-specific neurons. The present study combined the advantages of traditional morphological and electrophysiological methods with machine learning to address the shortcomings of the past method, to establish a classification model for the morphological and electrophysiological properties of mPFC pyramidal neurons, and to achieve more accurate and efficient identification of the properties from a small size sample of neurons. We labeled MD-innervated pyramidal neurons of mPFC using the trans-synaptic neural circuitry tracing method and obtained their morphological properties using whole-cell patch-clamp recording and morphologic reconstructions. The results showed that the classification model established in the present study could predict the electrophysiological properties of MD-innervated pyramidal neurons based on their morphology. MD-innervated pyramidal neurons exhibit larger basal dendritic length but lower apical dendrite complexity compared to non-MD-innervated neurons in the mPFC. The morphological characteristics of the two subtypes (ET-1 and ET-2) of mPFC pyramidal neurons innervated by MD are different, with the apical dendrites of ET-1 neurons being longer and more complex than those of ET-2 neurons. These results suggest that the electrophysiological properties of MD- innervated pyramidal neurons within mPFC correlate with their morphological properties, indicating that the different roles of these two subclasses in local circuits within PFC, as well as in PFC-cortical/subcortical brain region circuits.

Lipidomics reveals the significance and mechanism of the cellular ceramide metabolism for rotavirus replication.

As one of the most important causative agents of severe gastroenteritis in children, piglets, and other young animals, species A rotaviruses have adversely impacted both human health and the global swine industry. Vaccines against rotaviruses (RVs) are insufficiently effective, and no specific treatment is available. To understand the relationships between porcine RV (PoRV) infection and enterocytes in terms of the cellular lipid metabolism, we performed an untargeted liquid chromatography mass spectrometry (LC-MS) lipidomics analysis of PoRV-infected IPEC-J2 cells. Herein, a total of 451 lipids (263 upregulated lipids and 188 downregulated lipids), spanning sphingolipid, glycerolipid, and glycerophospholipids, were significantly altered compared with the mock-infected group. Interestingly, almost all the ceramides among these lipids were upregulated during PoRV infection. LC-MS analysis was used to validated the lipidomics data and demonstrated that PoRV replication increased the levels of long-chain ceramides (C16-ceramide, C18-ceramide, and C24-ceramide) in cells. Furthermore, we found that these long-chain ceramides markedly inhibited PoRV infection and that their antiviral actions were exerted in the replication stage of PoRV infection. Moreover, downregulation of endogenous ceramides with the ceramide metabolic inhibitors enhanced PoRV propagation. Increasing the levels of ceramides by the addition of C6-ceramide strikingly suppressed the replication of diverse RV strains. We further found that the treatment with an apoptotic inhibitor could reverse the antiviral activity of ceramide against PoRV replication, demonstrating that ceramide restricted RV infection by inducing apoptosis. Altogether, this study revealed that ceramides played an antiviral role against RV infection, providing potential approaches for the development of antiviral therapies.IMPORTANCERotaviruses (RVs) are among the most important zoonosis viruses, which mainly infected enterocytes of the intestinal epithelium causing diarrhea in children and the young of many mammalian and avian species. Lipids play an essential role in viral infection. A comprehensive understanding of the interaction between RV and lipid metabolism in the enterocytes will be helpful to control RV infection. Here, we mapped changes in enterocyte lipids following porcine RV (PoRV) infection using an untargeted lipidomics approach. We found that PoRV infection altered the metabolism of various lipid species, especially ceramides (derivatives of the sphingosine). We further demonstrated that PoRV infection increased the accumulation of ceramides and that ceramides exerted antiviral effects on RV replication by inducing apoptosis. Our findings fill a gap in understanding the alterations of lipid metabolism in RV-infected enterocytes and highlight the antiviral effects of ceramides on RV infection, suggesting potential approaches to control RV infection.

Isolation and characterization of a G9P[23] porcine rotavirus strain AHFY2022 in China.

Rotavirus group A (RVA) is a main pathogen causing diarrheal diseases in humans and animals. Various genotypes are prevalent in the Chinese pig herd. The genetic diversity of RVA lead to distinctly characteristics. In the present study, a porcine RVA strain, named AHFY2022, was successfully isolated from the small intestine tissue of piglets with severe diarrhea. The AHFY2022 strain was identified by cytopathic effects (CPE) observation, indirect immunofluorescence assay (IFA), electron microscopy (EM), high-throughput sequencing, and pathogenesis to piglets. The genomic investigation using NGS data revealed that AHFY2022 exhibited the genotypes G9-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1, using the online platform the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) (https://www.bv-brc.org/). Moreover, experimental inoculation in 5-day-old and 27-day-old piglets demonstrated that AHFY2022 caused severe diarrhea, fecal shedding, small intestinal villi damage, and colonization in all challenged piglets. Taken together, our results detailed the virological features of the porcine rotavirus G9P[23] from China, including the whole-genome sequences, genotypes, growth kinetics in MA104 cells and the pathogenicity in suckling piglets.

Inhibition of GluN2B-containing NMDA receptors in early life combined with social stress in adulthood leads to alterations in prefrontal PNNs in mice.

Perineuronal nets (PNNs) are specialized extracellular matrix (ECM) structures present in the central nervous system (CNS) and have been identified as significant regulators of developmental plasticity in the developing cortex. PNNs are particularly enriched in the cortex surrounding parvalbumin-expressing (PV+) cells. A growing body of evidence suggests that the abnormalities in PV+ neurons and PNNs are associated with various neurological disorders, including schizophrenia, which is a neurodevelopmental defect disease. The N-methyl-D-aspartate receptor (NMDAR) selective antagonist is frequently employed to establish animal models of schizophrenia in laboratory settings. The crucial involvement of GluN2B-containing NMDARs in the development of CNS has been extensively established. However, the role of GluN2B in the pathophysiology of schizophrenia has yet to be thoroughly investigated. The present study inhibited GluN2B function through intraperitoneal infusion of the GluN2B selective antagonist ifenprodil into juvenile mice aged 3-4 weeks, followed by the administration of social stress when these mice reached 9 weeks of age. Then, immunofluorescence staining was employed to examine the changes in the PNNs and PV+ cells, an acoustic startle and prepulse inhibition test was used to detect activities of the PV+ cells, and Western blot was used to quantify the protein expression levels of GluN2A and GluN2B in the prefrontal cortex (PFC). The study revealed that in the PFC of mice subjected to GluN2B antagonist treatment in early life and social stress in adulthood, there was an increase in the number of PV+ cells wrapped by PNNs, and a decrease in the activation of PV+ cells during the prepulse inhibition test, which is an indicator of sensory gating functions, as well as changes in the protein expression levels of GluN2A and GluN2B, which resulted in an increase in the ratio of GluN2A to GluN2B. These aberrations in the mice are comparable to those observed in animal models and patients with schizophrenia. The findings suggest that even a transient hypofunction of GluN2B in early life poses a significant risk for the emergence of schizophrenia symptoms in adulthood.

Construction of CdS@g-C3N4 heterojunction photocatalyst for highly efficient degradation of gaseous toluene.

Exploring efficient photocatalysts for the degradation of VOCs under visible light is a challenge. CdS@g-C3N4 heterojunction photocatalytic materials were developed in this study using a microwave-assisted sol-gel process. CdS@g-C3N4(0.2) photocatalyzed the maximum degradation of gaseous toluene under visible light irradiation, and the time required to achieve the same degradation rate was reduced by 270 min when compared to pure CdS. The morphological characterization, photoelectric property analysis, and DFT calculations all verified that the CdS nanoparticles were uniformly disseminated on the surface of g-C3N4, and that the interfaces were closely contacted to form a heterojunction interface with a built-in field. This enhances charge transfer from CdS to g-C3N4 while successfully decreasing electron-hole pair recombination caused by light. Furthermore, the energy band structure was altered to absorb longer wavelengths of light and extend the absorption spectral range, improving the photocatalytic material's efficacy for broad-spectrum light such as sunshine. This paper proposes methods for predicting and optimizing the surface structure of catalysts, as well as developing high-performance multi-heterojunction photocatalysts for the degradation of indoor VOCs.

Effects of the COVID-19 pandemic on stress, coping, and well-being among adults with histories of child maltreatment.

A number of studies now confirm that the COVID-19 pandemic has increased and exacerbated mental health problems in the general population. Previous quantitative studies have found similar effects on mental health symptoms among adults with histories of childhood adversity; however, qualitative research is needed to provide a more in-depth understanding of pandemic-related experiences among this vulnerable population. Using semistructured qualitative interviews, we explored perceptions of adults with histories of child maltreatment and neglect to better understand the overall impact of the pandemic on their mental health, reported changes in stress and alcohol use, and reported coping strategies during the first year of the pandemic (N = 40). Approximately half of participants reported that the pandemic had greatly (negatively) impacted their life, relationships, and well-being. Contributing stressors included being fearful of getting sick, navigating work changes, and experiencing economic and housing hardships, grief and loss, and social isolation. Fewer than half of the sample reported more stress (46%), whereas a third (33%) indicated no changes to stress, and 10% had reduced stress. The majority (80%) indicated no changes in their alcohol use. Most participants reported they used positive coping strategies during the pandemic. Three primary themes emerged related to participants' perceptions of getting through difficult times: seeking outside support, engaging in positive reframing, and drawing on internal strength and resources. Findings can guide prevention strategies that strengthen social support and foster resilience among vulnerable populations of adults with histories of childhood maltreatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effects of decabromodiphenyl ether on genes and signaling pathways related to subcutaneous transplanted tumors of cervical cancer in mice / 预防医学

Objective@#To investigate the effects of decabromodiphenyl ether (BDE-209) on the size of subcutaneous transplanted tumors, related genes and signaling pathways of cervical cancer in mice.@*Methods@#Forty female C57BL/6 mice were subcutaneously inoculated with mouse cervical carcinoma U14 cells in the lateral axilla to establish a mouse subcutaneous transplanted tumor model. These mice were randomly divided into a high-dose group (500 mg/kg), a medium-dose group (100 mg/kg), a low-dose group (20 mg/kg) and a control group (corn oil), and were exposed to BDE-209 or corn oil by gavage. Subcutaneous transplanted tumor tissue was taken after 21 days of BDE-209 poisoning, and the differentially expressed genes in the subcutaneous transplanted tumors of cervical cancer among the four groups were analyzed by high-throughput transcriptome sequencing and were subjected to Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Protein-protein interactions (PPI) were analyzed using the STRING database, and the mRNA expression of hub genes was determined by real-time fluorescence polymerase chain reaction.@*Results@#Compared with the control group, low-dose group and medium-dose group, the mass of subcutaneous transplanted tumors in the high-dose group was decreased (all P<0.05). Transcriptome sequencing results showed that compared with the control group, 2 011 genes were up-regulated and 1 165 genes were down-regulated in the high-dose group; 960 genes were up-regulated and 357 genes were down-regulated in the medium-dose group; 537 genes were up-regulated and 262 genes were down-regulated in the low-dose group (all P<0.05). GO and KEGG analysis showed that the differentially expressed genes in the high-dose group were mainly involved in cell chemotaxis and NOD-like receptor signaling pathway; the differentially expressed genes in the medium-dose group were mainly involved in cell chemotaxis and cytokine-cytokine receptor interactions; and the differentially expressed genes in the medium-dose group were mainly involved in processing and presentation of antigens, and the signaling pathways of the complement and coagulation cascades. Compared with the control group, the mRNA expression of TLR2, MMP9, IL-6, Fos, and TNF was up-regulated in the high-dose group (all P<0.05).@*Conclusion@#High-dose BDE-209 may affect Toll-like receptors, NOD-like receptors, and other immune and inflammatory-related signaling pathways and cancer-related genes, leading to a decrease in the mass of subcutaneous transplanted cervical cancer tumors in mice.

Low-Cytotoxicity, Broad-Spectrum Corn Starch-Based Antibacterial Particles that Inhibit Multidrug-Resistant Bacteria.

Antimicrobial resistance is a serious problem in biomedical applications that seriously increases the risk of medical failure. Therefore, developing highly efficient antibacterial agents that inhibit the growth of multidrug-resistant bacteria is a long-standing research goal. In this report, a low-cytotoxicity and highly efficient alternative to antibiotics was designed and prepared using edible corn starch as the scaffold and 2-hydroxypropyl-trimethylammonium chloride chitosan (HTCC) as the antimicrobial agent. The HTCC/starch particles were found to have a positively charged surface over a wide pH range and to possess broad-spectrum and highly efficient antimicrobial properties. These particles inhibited the growth of standard Gram-positive and Gram-negative bacteria from the China Pharmacopoeia and a clinical multidrug-resistant bacterial strain. Moreover, after treating the HTCC/starch particles with simulated gastric fluid (SGF, pH 1.2) for 4 h, the growth of clinical multidrug-resistant Escherichia coli (NT 2036) was inhibited effectively, indicating that these particles tolerate a gastric acid environment. Although the mass of SGF-treated HTCC/starch particles required to achieve similar antibacterial activity was ∼20-fold that of chloramphenicol or ampicillin, antibiotic-containing products require considerable amounts of pharmaceutical excipients to prepare. Therefore, the HTCC/starch particles described herein are potentially cost-effective alternatives to antibiotics that resolve the antimicrobial resistance issue, especially for inhibiting the growth of pathogenic intestinal bacteria.

Simple synthesis of BiOI/ZnO/rGO for efficient photocatalytic degradation of antibiotic chloramphenicol under visible light.

BiOI/ZnO/rGO (reduced graphene oxide) composite photocatalyst was fabricated using a simple one-step hydrothermal process and applied to the degradation of antibiotic chloramphenicol (CAP). By tuning the Bi/Zn ratios, the structure and photoelectric properties of the catalyst were investigated and characterized in terms of their morphological, structural, optical and photoelectrochemical properties. The as-synthesized composite photocatalysts are well-crystalline, uniform dispersion and exhibit good photocatalytic properties. The photocatalytic degradation rate of CAP by BiOI/ZnO/rGO composite is 8.1 times and 1.8 times that of BiOI and ZnO, respectively. The photocatalytic mechanism studies revealed that the synergistic effect between rGO and BiOI/ZnO can effectively separate photogenerated electron-hole, enhance photocurrents and conductivity, and improve charge carrier densities. Moreover, BiOI/ZnO/rGO possesses good stability and reusability that the degradation efficiency remained above 80% even after 5 recycling. This study reveals that both the introduction of rGO and heterostructure construction between BiOI and ZnO play a crucial role in their photoelectrochemical and photocatalytic properties.

Influence of wearing mouthguards on performance among athletes: A systematic review.

OBJECTIVES: While the use of mouthguards is well established to prevent orofacial and dental trauma occurrence, limited evidence exists regarding their influence on athletic performance. The objective of this study was to conduct a systematic review of the literature to assess the effect of wearing mouthguards on athletic performance. DESIGN: Systematic review. METHODS: An extensive search was performed in the databases of PubMed/MEDLINE, Embase, Scopus and Cochrane Library for studies published up to August 2022. Only peer-reviewed studies involving humans in vivo and investigating the use of mouthguards on performance among athletes were included. Quality assessment was performed using the Cochrane Collaboration's risk of bias tool. RESULTS: The initial query yielded 4785 citations, of which 41 studies met the inclusion criteria, comprising a total of 852 athletes. Overall, wearing mouthguards was found to improve athletic performance compared to the control group (without mouthguards). Custom-made mouthguards were found to be more effective in enhancing athletic performance compared to other types of mouthguards. CONCLUSIONS: Wearing mouthguards should be advocated by athletes not only for the prevention of orofacial and dental trauma but also for their potential improvements in athletic performance in specific actions. However, caution must be exercised in interpreting these findings due to the variability in outcome measures and the lack of important methodological details.

Correlation between the IgG/IgA Antibody Response against PEDV Structural Protein and Virus Neutralization.

Porcine epidemic diarrhea (PED) is a highly contagious intestinal infectious disease caused by porcine epidemic diarrhea virus (PEDV). Large-scale outbreaks of PEDV have caused huge economic losses to the pig industry since 2010. Neutralizing antibodies play a pivotal role in protecting piglets from enteric infections. However, there has been no systematic report on the correlations between neutralizing antibody titers (NTs) and absorbance values of IgG or IgA to all PEDV individual structural proteins in clinical serum, fecal, and colostrum samples. In this study, the spike protein S1 domain (S1), membrane protein (M), envelope protein (E), and nucleocapsid protein (N) of the variant PEDV strain AH2012/12 were expressed and purified by using the human embryonic kidney (HEK) 293F expression system. A total of 92 clinical serum samples, 46 fecal samples, and 33 colostrum samples were collected, and the correlations between IgG or IgA absorbance values and NTs were analyzed. R2 values revealed that anti-S1 IgA absorbance values show the highest agreement with NTs in all serum, fecal, and colostrum samples, followed by the N protein. The correlations between anti-E or M IgA and NTs were very low. However, in the colostrum samples, both IgG and IgA to S1 showed high correlations with NTs. In addition, compared with E and M, the highest correlations of IgA absorbance values were with N and S1 in serum and fecal samples. Overall, this study revealed the highest correlation between NTs and IgA to PEDV S1 protein. Therefore, the diagnostic method with anti-S1 IgA can be used as a powerful tool for assessing the immune status of pigs. IMPORTANCE The humoral immune response plays an important role in virus neutralization. Against PEDV, both IgG and the mucosal immune component IgA play roles in virus neutralization. However, which plays a more prominent role and whether there are differences in different tissue samples are not clearly reported. Additionally, the relationship between IgG and IgA against individual structural proteins and viral neutralization remains unclear. In this study, we systematically determined the relationship between IgG and IgA against all PEDV structural proteins and viral neutralization in different clinical samples and found the highest correlation between neutralization activity and IgA to PEDV S1 protein. Our data have important guiding implications in the evaluation of immune protection.

Clinical manifestations of COVID-19 infection in dialysis patients and protective effect of COVID-19 vaccine.

BACKGROUND AND OBJECTIVE: COVID-19 infection poses a special challenge to patients with dialysis patients. The purpose of this study was to evaluate the clinical manifestations of dialysis patients with COVID-19 and the protective effect of the vaccine. METHODS: We included 41 studies based on big data, mainly analyzing the clinical symptoms of dialysis patients with COVID-19, the proportion of severe patients before and after vaccination, and the humoral reaction of vaccine in the body. RESULTS: 6.1% to 35.7% of dialysis patients with COVID-19 developed respiratory distress symptoms and needed to be admitted to an intensive care unit for mechanical ventilation. The incidence and mortality of COVID-19 in dialysis patients before vaccination were 5.5% and 1.1%, respectively, and decreased to 4.5% and 0.6% in breakthrough infected patients. There was no statistical difference in serum conversion rates between dialysis patients and healthy controls, but the neutralizing antibody titer in the control group was 1922 (IQR 533 to 3186) AU/mL, and the neutralizing antibody titer in dialysis patients significantly decreased to 367 (IQR 171 to 1650) AU/mL (P=0.046). CONCLUSIONS: Dialysis is associated with an increased risk of severe COVID-19, and generally has a poor seroconversion response to vaccines. It also confirms the protective effect of vaccines on high-risk populations such as dialysis.