The Stiffness of the Ascending Aorta Has a Direct Impact on Left Ventricular Function: An In Silico Model.

During systole, longitudinal shortening of the left ventricle (LV) displaces the aortic root toward the apex of the heart and stretches the ascending aorta (AA). An in silico study (Living Left Heart Human Model, Dassault Systèmes Simulia Corporation) demonstrated that stiffening of the AA affects myocardial stress and LV strain patterns. With AA stiffening, myofiber stress increased overall in the LV, with particularly high-stress areas at the septum. The most pronounced reduction in strain was noted along the septal longitudinal region. The pressure-volume loops showed that AA stiffening caused a deterioration in LV function, with increased end-systolic volume, reduced systolic LV pressure, decreased stroke volume and effective stroke work, but elevated end-diastolic pressure. An increase in myofiber contractility indicated that stroke volume and effective stroke work could be recovered, with an increase in LV end-systolic pressure and a decrease in end-diastolic pressure. Longitudinal and radial strains remained reduced, but circumferential strains increased over baseline, compensating for lost longitudinal LV function. Myofiber stress increased overall, with the most dramatic increase in the septal region and the LV apex. We demonstrate a direct mechanical pathophysiologic link between stiff AA and reduced longitudinal left ventricular strain which are common in patients with HFpEF.

Nocardia implantans sp. nov. isolated from a patient with pulmonary infection.

TwoGram-stain-positive and rod-shaped actinomycetes (strains CDC186T and CDC192) were isolated from sputum samples of a patient in Chongqing, PR China, and were investigated to determine their taxonomic status. The results of phylogenetic analysis based on the 16S rRNA gene indicated that CDC186T and CDC192 represented members of the genus Nocardia, and the sequence similarity with Nocardia beijingensis DSM 44636T was the highest, at 99.71 and 99.78 %, respectively. The DNA G+C content of both CDC186T and CDC192 was 69.1 %. Genomic diversity analysis revealed that the average nucleotide identity and in silico DNA‒DNA hybridisation values between the two novel strains and closely related species were significantly below the thresholds of 95-96 and 70 %, respectively, but these values between the two novel strains were 99.96 and 99.90 %, respectively. The phylogenetic relationship based on the dapb1 gene and the single-copy core genes further indicated that the two novel strains were clustered in separate branch adjacent to N. beijingensis DSM 44636T. Growth occurred within the ranges of 20-42 °C, pH 6.0-9.0 and NaCl concentrations of 0.5-4.5 % (w/v). The major fatty acids of CDC186T and CDC192 were C16 : 0 and C18 : 0 10-methyl [tuberculostearic acid (TBSA)]. The predominant respiratory menaquinone was MK-9. The polar lipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannoside, one unidentified glycolipid, one unidentified phospholipid and one unidentified phosphoglycolipid. All the genomes of the studied strains were annotated with virulence factor (VF)-associated genes homologous to those of Mycobacterium tuberculosis, and the results of susceptibility testing indicated that CDC186T and CDC192 were resistant to amoxicillin-clavulanic acid and tigecycline. On the basis of chemotaxonomic characteristics and the results of phylogenetic analyses, strains CDC186T and CDC192 represent a novel species within the genus Nocardia, for which the name Nocardia implantans sp. nov. is proposed. The type strain is CDC186T (=GDMCC 4.206T= JCM 34959T).

Capture of armA by a novel ISCR element, ISCR28.

ISCR28 is a fully functional and active member of the IS91-like family of insertion sequences. ISCR28 is 1,708-bp long and contains a 1,293-bp long putative open reading frame that codes a transposase. Sixty ISCR28-containing sequences from GenBank generated 27 non-repeat genetic contexts, all of which represented naturally occurring biological events that had occurred in a wide range of gram-negative organisms. Insertion of ISCR28 into target DNA preferred the presence of a 5'-GXXT-3' sequence at its terIS (replication terminator) end. Loss of the first 4 bp of its oriIS (origin of replication) likely caused ISCR28 to be trapped in ISApl1-based transposons or similar structures. Loss of terIS and fusion with a mobile element upstream likely promoted co-transfer of ISCR28 and the downstream resistance genes. ArmA and its downstream intact ISCR28 can be excised from recombinant pKD46 plasmids forming circular intermediates, further elucidating its activity as a transposase.

Origin of photoinduced DC current and two-level population dynamics in a single molecule.

Studying the photoinduced changes of materials with atomic-scale spatial resolution can provide a fundamental understanding of light-matter interaction. A long-standing impediment has been the detrimental thermal effects on the stability of the tunneling gap from intensity-modulated laser irradiation of the scanning tunneling microscope junction. Photoinduced DC current transduces photons to an electric current and is widely applied in optoelectronics as switches and signal transmission. Our results revealed the origin of the light-induced DC current and related it to the two-level population dynamics and related nonlinearity in the conductance of a single molecule. Here, we compensated for the near-visible laser-induced thermal effects to demonstrate photoinduced DC current spectroscopy and microscopy and to observe the persistent photoconductivity of a two-level pyrrolidine molecule. The methodology can be generally applied to the coupling of light to scan probes to investigate light-matter interactions at the atomic scale.

In Situ Formation of a LiBO2 Coating Layer and Spinel Phase for Ni-Rich Cathode Materials from a Boric Acid-Etched Precursor.

Ni-rich cathode materials exhibit superior energy densities and have attracted interest among both research and industrial fields; whereas, their practical application is hindered by the intrinsic drawbacks brought by the high nickel content such as structural instability and rapid capacity fading. Herein, in situ formation of a LiBO2 coating layer and spinel phase layer is achieved on the surface of a Ni-rich cathode material via a boric acid etching method at the precursor state. The spinel phase is considered to have a 3D lithium diffusion tunnel and hence faster diffusion kinetics. Moreover, the LiBO2 layer possesses excellent (electro)chemical inertness and can suppress electrolyte decomposition, resulting in a more inorganic and stable cathode-electrolyte interface. The surface reconstructed sample exhibits better cyclic stability (93.3% capacity retention vs 85.3% for the pristine sample at 1 C for 100 cycles) and rate performance. The superiority of this surface reconstruction is demonstrated by a series of electrochemical techniques and characterization methods including high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), post-mortem X-ray photoelectron spectroscopy (XPS) analysis, and density functional theory (DFT) calculations.

Single-cell metabolic fingerprints discover a cluster of circulating tumor cells with distinct metastatic potential.

Circulating tumor cells (CTCs) are recognized as direct seeds of metastasis. However, CTC count may not be the "best" indicator of metastatic risk because their heterogeneity is generally neglected. In this study, we develop a molecular typing system to predict colorectal cancer metastasis potential based on the metabolic fingerprints of single CTCs. After identification of the metabolites potentially related to metastasis using mass spectrometry-based untargeted metabolomics, setup of a home-built single-cell quantitative mass spectrometric platform for target metabolite analysis in individual CTCs and use of a machine learning method composed of non-negative matrix factorization and logistic regression, CTCs are divided into two subgroups, C1 and C2, based on a 4-metabolite fingerprint. Both in vitro and in vivo experiments demonstrate that CTC count in C2 subgroup is closely associated with metastasis incidence. This is an interesting report on the presence of a specific population of CTCs with distinct metastatic potential at the single-cell metabolite level.

Simultaneous quantification of multiple single nucleotide variants in PIK3CA ctDNA using mass-tagged LCR probe sets.

Circulating tumor DNA (ctDNA) in blood carries genetic variations associated with tumors. There is evidence indicating that the abundance of single nucleotide variant (SNV) in ctDNA is correlated well with cancer progression and metastasis. Thus, accurate and quantitative detection of SNVs in ctDNA may benefit clinical practice. However, most current methods are unsuitable for the quantification of SNV in ctDNA that usually differentiates from wild-type DNA (wtDNA) only by a single base. In this setting, ligase chain reaction (LCR) coupled with mass spectrometry (MS) was developed to simultaneously quantify multiple SNVs using PIK3CA ctDNA as a model. Mass-tagged LCR probe set for each SNV including mass-tagged probe and three DNA probes was firstly designed and prepared. Then, LCR was initiated to discriminate SNVs specifically and amplify the signal of SNVs in ctDNA selectively. Afterward, a biotin-streptavidin reaction system was used to separate the amplified products, and photolysis was initiated to release mass tags. Finally, mass tags were monitored and quantified by MS. After optimizing conditions and verifying performance, this quantitative system was applied for blood samples from breast cancer patients, and risk stratification for breast cancer metastasis was also performed. This study is among the first to quantify multiple SNVs in ctDNA in a signal amplification and conversion manner, and also highlights the potential of SNV in ctDNA as a liquid biopsy marker to monitor cancer progression and metastasis.

Accurate, Sensitive, and Rapid Detection of Pseudomonas aeruginosa Based on CRISPR/Cas12b with One Fluid-Handling Step.

Pseudomonas aeruginosa is a major bacterial pathogen causing nosocomial infections and accounts for morbidity and mortality among patients with cystic fibrosis. An accurate, sensitive, and rapid method to detect P. aeruginosa is critical for the early control of infection and patient management. In this study, we established a P. aeruginosa clustered regularly interspaced short palindromic repeats testing in one pot (CRISPR-top) assay which detected P. aeruginosa with one fluid-handling step in one tube. The reaction was performed isothermally within 1 h; thus, specific instruments were not required. The optimal reaction conditions of this assay were determined to be a temperature of 55°C; working concentrations of 1 µM for the forward inner primer and backward inner primer, 0.5 µM for the loop forward primer and loop backward primer, and 0.25 µM for the forward outer primer and backward outer primer; as well as a 2 µM concentration single-stranded DNA reporter molecules. In terms of specificity, our assay showed 100% inclusivity and exclusivity among 48 strains, including 15 P. aeruginosa clinical isolates and 33 non-P. aeruginosa strains. The limit of detection of our method was 10 copies per reaction mixture. Forty-six human sputum specimens from patients with respiratory symptoms were tested. Using the results of quantitative real-time PCR as the gold standard, our method showed 85.3% (29/34) sensitivity, 100% (12/12) specificity, a positive predictive value of 100% (29/29), and a negative predictive value of 70.6% (12/17). In summary, the P. aeruginosa CRISPR-top assay developed in the present study is a high-efficiency alternative tool for the accurate and rapid detection of P. aeruginosa, especially in resource-limited settings. IMPORTANCE This study reports a P. aeruginosa CRISPR-top assay which can precisely identify P. aeruginosa using nucleic acids from pure cultures or clinical samples in one pot with one fluid-handling step. The P. aeruginosa CRISPR-top reaction is suitable for on-site testing, and its diagnostic performance can be compared with that of qPCR.

Epidemiological Investigation of Hospital Transmission of Corynebacterium striatum Infection by Core Genome Multilocus Sequence Typing Approach.

Corynebacterium striatum has recently received increasing attention due to its multiple antimicrobial resistances and its role as an invasive infection/outbreak agent. Recently, whole-genome sequencing (WGS)-based core genome multilocus sequence typing (cgMLST) has been used in epidemiological studies of specific human pathogens. However, this method has not been reported in studies of C. striatum. In this work, we aim to propose a cgMLST scheme for C. striatum. All publicly available C. striatum genomes, 30 C. striatum strains isolated from the same hospital, and 1 epidemiologically unrelated outgroup C. striatum strain were used to establish a cgMLST scheme targeting 1,795 genes (hereinafter referred to as 1,795-cgMLST). The genotyping results of cgMLST showed good congruence with core genome-based single-nucleotide polymorphism typing in terms of tree topology. In addition, the cgMLST provided a greater discrimination than the MLST method based on 6 housekeeping genes (gyrA, gyrB, hsp65, rpoB, secA1, and sodA). We established a clonal group (CG) threshold based on 104 allelic differences; a total of 56 CGs were identified from among 263 C. striatum strains. We also defined an outbreak threshold based on seven allelic differences that is capable of identifying closely related isolates that could give clues on hospital transmission. According to the results of analysis of drug-resistant genes and virulence genes, we identified CG4, CG5, CG26, CG28, and CG55 as potentially hypervirulent and multidrug-resistant CGs of C. striatum. This study provides valuable genomic epidemiological data on the diversity, resistance, and virulence profiles of this potentially pathogenic microorganism. IMPORTANCE Recently, WGS of many human and animal pathogens has been successfully used to investigate microbial outbreaks. The cgMLST schema are powerful genotyping tools that can be used to investigate potential epidemics and provide classification of the strains precise and reliable. In this study, we proposed the development of a cgMLST typing scheme for C. striatum, and then we evaluated this scheme for its applicability to hospital transmission investigations. This report describes the first cgMLST schema for C. striatum. The analysis of hospital transmission of C. striatum based on cgMLST methods has important clinical epidemiological significance for improving nosocomial infection monitoring of C. striatum and in-depth understanding of its nosocomial transmission routes.

Three novel Cas12a orthologs with robust DNA cleavage activity suitable for nucleic acid detection.

Developing rapid and accurate pathogen detection methods is increasingly important, and CRISPR-Cas system can be optimized for this purpose. CRISPR-Cas12a is a single RNA-guided endonuclease system with the potential for nucleic acid detection. There is a broad diversity among Cas12a nucleases with robust detection capability. Herein, we characterised three Cas12a orthologs (ObCas12a, MbCas12a, and ScCas12a), including cis- and trans-cleavage activities, the identification of PAM, single-base resolution ability, and the application for nucleic acid detection. These Cas12a orthologs displayed robust cis- and trans-cleavage activities, and performed well in terms of specificity and sensitivity for nucleic acid detection. Furthermore, they have subtle differences in single-base resolution and recognised PAM sites in vitro. Therefore, these Cas12a nucleases are candidate proteins for CRISPR-based diagnostic methods. Addition of these enzymes to the nucleic acid detection toolbox will further expand the utility of this powerful technology.

Analysis of associated factors of the inconsistency for knowledge and behavior in condom use among college students in Zhuhai City / 中国学校卫生

Objective@#To examine the prevalence and factors influencing the inconsistency for knowledge and behavior in condom use among college students, so as to provide suggestions for AIDS prevention and education in universities.@*Methods@#From October to December 2019, a multistage cluster sampling method was employed to collect data relating to inconsistency for knowledge and behavior in condom use and other related factors among 1 303 students from six colleges in Zhuhai, China. Chi square test and Logistic regression were performed to analyze the influencing factors and moderating effect.@*Results@#The reporting rate of in consistency of knowledge and behavior in condom use among college students was 41.1%. Multivariate Logistic regression analysis showed that seeking sexual partners offline was negatively correlated with inconsistency for knowledge and behavior in condom use ( OR=0.70, 95%CI =0.51-0.95). However, condom nonuse during the first sexual experience (OR=7.11, 95%CI=5.23-9.67), smoking before sex ( OR=1.47, 95%CI =1.07-2.02), drinking before sex ( OR=1.44, 95%CI =1.09-1.91), history of intimate partner violence ( OR=1.53, 95%CI =1.13-2.07), and having multiple sexual partners ( OR=1.69, 95%CI =1.25-2.29) were positively correlated with inconsistency for knowledge and behavior in condom use ( P <0.05). The moderating effect analysis showed that condom use during the first sexual experience had a moderating effect on smoking before sex and inconsistency for knowledge and behavior in condom use ( β=0.92, P <0.05). Among students who did not use condoms during the first sexual experience, a positive correlation was observed between smoking before sex and inconsistency for knowledge and behavior in condom use ( OR= 2.76 , 95%CI=1.09-6.99, P <0.05). However, no correlation was found between smoking before sex and inconsistency for knowledge and behavior in condom use ( OR=1.32, 95%CI=0.92-1.88, P >0.05) among students who used condoms during the first sexual experience.@*Conclusion@#High levels of inconsistency for knowledge and behavior in condom use are found among college students in Zhuhai City. Colleges should carry out sex education activities as soon as possible, and explore new health education models to promote the transformation of their knowledge into behavior.

Compliance with enhanced recovery after surgery protocol in geriatric patients with fresh fracture / 中华创伤骨科杂志

Objective:To analyze the compliance with enhanced recovery after surgery (ERAS) protocol in geriatric patients with fresh fracture.Methods:A retrospective study was conducted on the data of the patients with fresh extremity fracture which had been included in the ERAS perioperative protocol database during May 2019 and January 2022 at Department of Orthopaedic Trauma, Beijing Jishuitan Hospital. The patients ≥65 years were selected as a study group which was matched by a control group of the patients < 65 years in sex, fracture type and date frame of hospitalization at a ratio of 1∶1. The 2 groups were compared in the compliance with the 14 ERAS core perioperative elements.Results:The study group and the control group each included 66 patients who were matched in sex and fracture type. 62.1% (41/66) of the patients in the study group had combined diseases, significantly more than that [16.7% (11/66)] in the control group( P<0.001). Altogether, the compliance with the 14 ERAS core perioperative elements was 78.6 (71.4, 85.7) % in both groups, showing no significant difference between them ( P>0.05). Respectively, the compliance with the postoperative oral intake in the study group (80.3%, 53/66) was significantly lower than that in the control group (92.4%, 61/66) ( P<0.05); the compliance with the other 13 elements showed no statistically significant difference between the 2 groups ( P>0.05). Conclusion:The ERAS perioperative protocol can be carried out smoothly in geriatric patients with fresh fracture whose compliance may be comparable to that of the none-elderly patients.

Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures (version 2023) / 中华创伤杂志

Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.

Application of blended learning combined with Jigsaw teaching in arterial blood specimen collection of undergraduate intern nurses / 中华医学教育探索杂志

Objective:To explore the application effect of online and offline blended learning combined with Jigsaw teaching in arterial blood specimen collection of undergraduate nursing interns.Methods:A total of 135 undergraduate nursing interns were randomly divided into the experimental group ( n=66) and the control group ( n=69). The experimental group used the blended learning combined with Jigsaw teaching, while the control group adopted the blended learning combined with PBL teaching. The theoretical examination before and after class, the skill assessment after training, the nursing clinical decision-making consciousness scale, and the teaching satisfaction survey were conducted in the two groups. SPSS 28.0 was used for t-test and Chi-square test. Results:After teaching, the total score of courses and the score of theoretical examination and skill assessment of the experimental group were higher than those of the control group, and the differences were statistically significant ( P<0.05). The total score and the multi-dimension scores of the nursing clinical decision-making consciousness scale in the experimental group were higher than those in the control group, and the differences were statistically significant ( P<0.05). The teaching satisfaction of the experimental group was 92.42% (61/66), which was significantly higher than that of the control group [69.57% (48/69)], and the differences were statistically significant ( P<0.05). Conclusion:Blended learning combined with Jigsaw teaching is applied to collect arterial blood specimens for undergraduate nursing interns, which is beneficial to improve the academic performance and clinical decision-making ability of nursing students.

Clinical study of Tongbu Qijing Acupuncture combined with metformin hydrochloride tablet in the treatment of polycystic ovary syndrome combined with insulin resistance of kidney-deficiency phlegm dampness type / 国际中医中药杂志

Objective:To evaluate the effect of Tongbu Qijing Acupuncture combined with metformin hydrochloride tablet on polycystic ovary syndrome (PCOS) combined with insulin resistance (IR) of kidney-deficiency phlegm dampness type.Methods:Randomized controlled trial. 84 patients with PCOS and IR in the hospital were enrolled as the observation objects between November 2019 and November 2021. According to random number table method, they were divided into observation group (Tongbu Qijing Acupuncture combined with metformin hydrochloride tablets) and control group (oral metformin hydrochloride tablets), 42 in each group. All were treated for 3 courses of treatment (1 month/course). TCM syndromes were scored before and after treatment. The height, weight, waist circumference and hip circumference of patients were measured to calculate body mass index (BMI) and waist-hip ratio (WHR). The levels of serum TG, TC, LDL-C and HDL-C were detected by biochemical analyzer, fasting blood glucose (FPG) was detected by glucose oxidase method, fasting insulin (FINS) was detected by electrochemiluminescence method, and insulin resistance index (HOMA-IR) was calculated. The recovery rates of menstruation and ovulation were observed and compared after treatment, and the clinical curative effect was evaluated.Results:There were significant differences in total response rate between observation group and control group [95.24% (40/42) vs. 80.95% (34/42); χ2=4.09, P=0.043]. After treatment, scores of TCM syndromes, BMI and WHR in observation group were significantly lower than those in the control group ( t=20.36, 23.77, 3.44, P<0.01). After treatment, serum FPG [(4.86±0.51) nmol/L vs. (5.41±0.55) nmol/L, t=4.75], FINS [(8.31±0.85) mU/L vs. (10.11±1.02) mU/L, t=8.79] levels and HOMA-IR [(1.88±0.19) vs. (2.44±0.25), t=11.97] in observation group were significantly lower than those in the control group ( P<0.01). After treatment, levels of serum TG, TC and LDL-C in observation group were significantly lower than those in the control group ( t=16.54, 4.81, 5.35, P<0.01), while HDL-C was significantly higher than that of the control group ( t=6.78, P<0.01). After treatment, there were significant differences in recovery rates of menstruation and ovulation between observation group and control group [57.14% (24/42), 47.62% (20/42) vs. 80.95% (34/42), 69.05% (29/42); χ2=5.57, 3.97, P<0.05]. Conclusion:Tongbu Qijing Acupuncture combined with metformin hydrochloride tablet can effectively improve syndromes and signs, regulate glucose-lipid metabolism, reduce IR and promote the recovery of menstruation and ovulation in patients with PCOS and IR.

Minimally invasive techniques for lateral maxillary sinus floor elevation: small lateral window and one-stage surgery-a 2-5-year retrospective study / 国际口腔科学杂志·英文版

This study aimed to introduce a minimally invasive technique for maxillary sinus floor elevation using the lateral approach (lSFE) and to determine the factors that influence the stability of the grafted area in the sinus cavity. Thirty patients (30 implants) treated with lSFE using minimally invasive techniques from 2015 to 2019 were included in the study. Five aspects of the implant (central, mesial, distal, buccal, and palatal bone heights [BHs]) were measured using cone-beam computed tomography (CBCT) before implant surgery, immediately after surgery (T0), 6 months after surgery (T1), and at the last follow-up visit (T2). Patients' characteristics were collected. A small bone window (height, (4.40 ± 0.74) mm; length, (6.26 ± 1.03) mm) was prepared. No implant failed during the follow-up period (3.67 ± 1.75) years. Three of the 30 implants exhibited perforations. Changes in BH of the five aspects of implants showed strong correlations with each other and BH decreased dramatically before second-stage surgery. Residual bone height (RBH) did not significantly influence BH changes, whereas smoking status and type of bone graft materials were the potentially influential factors. During the approximate three-year observation period, lSFE with a minimally invasive technique demonstrated high implant survival rate and limited bone reduction in grafted area. In conclusion, lSFE using minimally invasive techniques was a viable treatment option. Patients who were nonsmokers and whose sinus cavity was filled with deproteinized bovine bone mineral (DBBM) had significantly limited bone resorption in grafted area.

Effect of repeated intravitreal Ranibizumab and Aflibercept injections on the corneal nerves in patients with macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of repeated intravitreal injection of ranibizumab and aflibercept on corneal nerve of patients with macular edema.METHODS: A total of 64 patients(64 eyes)enrolled in our hospital from June 2021 to June 2022 were treated with intravitreal injection of anti-vascular endothelial growth factor(VEGF). There were 20 cases(20 eyes)of diabetic macular edema, 19 cases(19 eyes)of wet age-related macular degeneration and 25 cases(25 eyes)of retinal vein occlusion. Corneal confocal microscope was used to collect images of corneal subbasal nerve plexus before injections and at 1mo after each intravitreal injection based on 3+pro re nata(PRN)treatment regimen. Furthermore, the length and density of corneal nerve were measured.RESULTS: There was no significant difference in corneal nerve density of patients injected with aflibercept between pre-injection and post-injection(P&#x003E;0.05), while the corneal nerve length after 2nd and 3rd injections was lower than that of pre-injection(all P&#x003C;0.01). There were no significant changes in corneal nerve density and length in patients with intravitreal injections of ranibizumab(all P&#x003E;0.05), and there was no significant differences in corneal nerve density and length after 3 injections of the two drugs(all P&#x003E;0.05).CONCLUSION: Repeated intravitreal anti-VEGF drug may affect corneal nerve to some extent. For patients who need repeated intravitreal injections of anti-VEGF, attention should be paid to the changes of corneal nerves.

Immunoprotective Analysis of the NFA49590 Protein from Nocardia farcinica IFM 10152 Demonstrates Its Potential as a Vaccine Candidate.

Nocardia is emerging as a serious and easily neglected pathogen in clinical practice with multidrug resistance that extends the treatment period for months or even years. This has led to the investigation of a vaccine approach to prevent Nocardia infections. However, studies on the protective proteins of Nocardia have not yet been carried out. In the present work, over 500 proteins in the supernatant of N. farcinica IFM10152 were identified by LC−MS/MS. In silico analysis of these proteins with a high content (score > 2000) predicted that NFA49590 was one of the conserved proteins in N. farcinica strains with potential antigenicity. After the rNFA49590 protein was cloned and expressed in E. coli (DE3) and purified using a Ni-NTA column, its good antigenicity was confirmed with sera from mice immunized with different Nocardia species by Western blot. Then we confirmed its ability to activate innate immunity by examining the phosphorylation status of ERK1/2, JNK, p38, and p65 and the cytokine levels of IL-6, TNF-α, and IL-10. Finally, we evaluated its immunoprotective effect in BALB/c mice, and we found that mice immunized with rNFA49590 protein exhibited high antibody titers, enhanced bacterial clearance ability, and generated robust protective effects from the N. farcinica challenge. These results offer strong support for the use of NFA49590 protein as a vaccine candidate and open the possibilities for the exploration of a large array of immunoprotective proteins.

Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response

The emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) variants and "anatomical escape" characteristics threaten the effectiveness of current coronavirus disease (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. In this study, we investigated immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants. Intranasal delivery of dNS1-RBD induced innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrained the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (IL-6, IL-1B, and IFN-{gamma}) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.

Atomic-Scale Rectification and Inelastic Electron Tunneling Spectromicroscopy.

The phenomenon of rectification describes the emergence of a DC current from the application of an oscillating voltage. Although the origin of this effect has been associated with the nonlinearity in the current-voltage I(V) relation, a rigorous understanding of the microscopic mechanisms for this phenomenon remains challenging. Here, we show the close connection between rectification and inelastic electron tunneling spectroscopy and microscopy for single molecules with a scanning tunneling microscope. While both techniques are based on nonlinear features in the I(V) curve, comprehensive line shape analyses reveal notable differences that highlight the two complementary techniques of nonlinear conductivity spectromicroscopy for probing nanoscale systems.