Thiol-gold (Au) conjugation is perhaps the most routinely applied surface chemistry approach to immobilize receptors within Au-based molecular sensing platforms. However, no previous studies have ...investigated in situ immobilization in a nanofluidic systems. In this work, flowthrough receptor immobilization is demonstrated, using a nanoslit induced depletion zone to enable direct real-time visualization for characterizing the effect of sodium chloride (NaCl) concentrations during immobilization of thiolated single-stranded DNA on Au. The results show that the amount of fixed-DNA on Au, as well as the non-specific adsorption of DNA on fused silica surface, strongly depend on NaCl levels. Furthermore, the non-specific interaction at high NaCl levels reduces the DNA available for immobilization on Au, but enriches the DNA molecules in the channel under wash by deionized water. By adding Tween-20 to decrease the non-specific adsorption and increasing the driving pressure to increase the DNA flux under high-salt level, the immobilization time can be further decreased to 10 min or less, which is at least an order of magnitude faster than recently proposed bioconjugation methods for thiolated-DNA–Au conjugation. Moreover, this work demonstrates the capability of the platform for DNA- and aptamer-based sensing assays, thereby opening up new strategies for developing biosensors using nanofluidic platforms.
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•Real-time visualization of DNA immobilization on Au surface in nanochannels.•The amounts of immobilized DNA on Au surface depend on the NaCl levels.•The adsorption of DNA on the fused silica surface depends on the NaCl levels.•Ultrarapid DNA immobilization on Au surface in the nanochannel (∼ 10 minutes).•Wash-free, real-time visualization for gene and protein detections
Nowadays, there has been increased awareness that the therapeutic effects of natural medicines on inflammatory diseases may be achieved by regulating the gut microbiota. Shuanghuanglian oral liquid ...(SHL), the traditional Chinese medicine preparation, has been shown to be effective in clearing heat-toxin, which is widely used in the clinical treatment of respiratory tract infection, mild pneumonia, and common cold with the wind-heat syndrome. Yet the role of gut microbiota in the antipyretic and anti-inflammatory effects is unclear. In this study, a new strategy of the 16S rRNA gene sequencing and serum metabolomics that aims to explore the role of SHL in a rat model of the systemic inflammatory response induced by lipopolysaccharide would be a major advancement. Our results showed that the gut microbiota structure was restored in rats with inflammation after oral administration of SHL, thereby reducing inflammation. Specifically, SHL increased the relative abundance of
Bacteroides
and
Faecalibacterium
and decreased the abundance of
Bifidobacterium
,
Olsenella
,
Aerococcus
,
Enterococcus
, and
Clostridium
in the rat model of inflammatory disease. Serum metabolomic profile obtained by the orbitrap-based high-resolution mass spectrometry revealed significant differences in the levels of 39 endogenous metabolites in the inflammatory model groups, eight metabolites of which almost returned to normal levels after SHL treatment. Correlation analysis between metabolite, gut microbiota, and inflammatory factors showed that the antipyretic and anti-inflammatory effects of SHL were related to the recovery of the abnormal levels of the endogenous metabolites (N-acetylserotonin and 1-methylxanthine) in the tryptophan metabolism and caffeine metabolism pathway. Taken together, these findings suggest that the structural changes in the gut microbiota are closely related to host metabolism. The regulation of gut microbiota structure and function is of great significance for exploring the potential mechanism in the treatment of lipopolysaccharide-induced inflammatory diseases with SHL.
Endometrial cancer (EC) is one of the most common gynecological cancers, and its risk factors include obesity and metabolic, genetic, and other factors. Recently, the circadian rhythm has also been ...shown to be associated with EC, as the severity of EC was found to be related to night work and rhythm disorders. Therefore, circadian rhythm disorders (CRDs) may be one of the metabolic diseases underlying EC. Changes in the circadian rhythm are regulated by clock genes (CGs), which in turn are regulated by non-coding RNAs (ncRNAs). More importantly, the mechanism of EC caused by ncRNA-mediated CRDs is gradually being unraveled. Here, we review existing studies and reports and explore the relationship between EC, CRDs, and ncRNAs.
•The burden of diarrhea attributed to diarrheagenic Escherichia coli (DEC) in China was high and increasing from 2009 to 2018, especially for three most frequent pathotypes including ...enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC).•Age profile of DEC prevalence and the pathotype composition was disclosed, which can help planning and adopting targeted preventive measures and antimicrobial therapy.•Regional difference between urban and rural areas were identified for the five DEC pathotypes in acute diarrheal patients.
Objectives To investigate the epidemiological features of diarrheagenic Escherichia coli (DEC) in patients with acute diarrhea in China.
Methods An active sentinel surveillance was performed in all-age patients with acute diarrhea in China, 2009‒2018. DEC was isolated and identified by serological assay and PCR from stool samples.
Results DEC was determined in 6.68% (6,119/91,651) of the patients, with higher positive rates among females than among males (6.97% vs. 6.46%) and among 18‒59 years patients (7.88%) than among other age groups. Five pathotypes were identified, the most prevalent was enteroaggregative E. coli (EAEC), followed by enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). Pediatric patients <5 years had higher positive rate of EAEC (2.07%), followed by EPEC (1.81%), and enterohemorrhagic E. coli (EHEC) (0.31%), while the 18‒59 years patients had higher infection of ETEC (2.36%). ETEC and EPEC were more frequently identified in urban than rural areas, with age and gender adjusted positive rate of 1.68% vs. 1.14% respectively, and 1.77% vs. 1.55%, while EIEC and EHEC were more frequently identified in rural areas.
Conclusions These findings highlight the epidemiology features of DEC and underscores the need for conducting DEC surveillance.
•For patients aged ≥ 80 years with moderate to severe acute cholecystitis, the morbidity and mortality rates of cholecystectomy are not high.•Early cholecystectomy (< 6 weeks) and delayed ...cholecystectomy (≥ 6 weeks) have similar rates in conversion surgery, perioperative complications, and operative mortality.•Early cholecystectomy has lower risks of recurrent acute cholecystitis and further biliary events compared with delayed cholecystectomy.
Acute cholecystitis (AC) is a life-threatening infectious/inflammatory disease in older patients. This study aimed to investigate the safety and optimal timing of surgery in patients aged ≥ 80 years with moderate to severe AC who received percutaneous transhepatic gallbladder drainage (PTGBD).
From January 2008 to February 2021, 152 patients were retrospectively enrolled. Clinical outcomes were compared among patients who received laparoscopic cholecystectomy (LC), open cholecystectomy (OC), and conversion surgery, and between those who received early (< 6 weeks after PTGBD) and delayed cholecystectomy (≥ 6 weeks after PTGBD). Logistic regression analysis was used to identify risk factors for recurrent AC, further biliary events, conversion, and perioperative complications.
Sixty-seven patients underwent LC, 62 underwent OC, and 23 underwent conversion surgery. Operation-related complications and mortality rates did not differ among the types of surgery; however, LC group had shorter operative time than the other groups. Eighty-two patients underwent early cholecystectomy, while 70 underwent delayed cholecystectomy. There were no differences in operative time, operation-related complications, and mortality rates between the groups. However, higher rates of recurrent AC and biliary events were observed in the delayed cholecystectomy group (52.9% vs. 4.9% and 57.1% vs. 8.5%, p < 0.001). On multivariate analysis, delayed cholecystectomy was a significant risk factor for recurrent AC (odds ratio OR = 19.42, p < 0.001) and further biliary events (OR = 15.95, p < 0.001).
Early cholecystectomy is recommended for patients aged ≥ 80 years with moderate to severe AC following PTGBD.
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Meta-analysis is a method for enhancing statistical power through the integration of information from multiple studies. Various methods for integrating p-values (i.e., statistical ...significance), including Fisher’s method under an independence assumption, the permutation method, and the decorrelation method, have been broadly used in bioinformatics and computational biotechnology studies. However, these methods have limitations related to statistical assumption, computing efficiency, and accuracy of statistical significance estimation. In this study, we proposed a numerical integration method and examined its theoretical properties. Simulation studies were conducted to evaluate its Type I error, statistical power, computational efficiency, and estimation accuracy, and the results were compared with those of other methods. The results demonstrate that our proposed method performs well in terms of Type I error, statistical power, computing efficiency (regardless of sample size), and statistical significance estimation accuracy. P-value data from multiple large-scale genome-wide association studies (GWASs) and transcriptome-wise association studies (TWASs) were analyzed. The results demonstrate that our proposed method can be used to identify critical genomic regions associated with rheumatoid arthritis and asthma, increase statistical significance in individual GWASs and TWASs, and control for false-positives more effectively than can Fisher’s method under an independence assumption. We created the software package Pbine, available at GitHub (https://github.com/Yinchun-Lin/Pbine).
Human parvovirus B19 (HPV B19) is pathogenic to human, which can cause fifth disease, transient aplastic crisis, arthritis, myocarditis, autoimmune disorders, hydrops fetalis, and so on. Currently, ...no approved vaccines or antiviral drugs are available against HPV B19, and thus the development of effective vaccines is needed. The capsid of HPV B19 is composed of two types of proteins, i.e., the major capsid protein VP2 and the minor protein VP1. Previous experimental studies have shown that the dominant immune responses against HPV B19 are elicited by VP1, especially the unique region on the N-terminus of VP1. It has been found that VP2 alone or VP2 and VP1 together can assemble into virus-like particle (VLP). The VLP structure formed by VP2 has been resolved, however, the location of VP1 in the capsid, especially the location of VP1 unique region with strong immunogenicity, is still not clear. In the present work, using the
expression system developed by our laboratory, two kinds of recombinant HPV B19 VLPs were expressed, i.e., the VLP co-assembled by VP1 and VP2 (VP1/VP2 VLP) and the VLP whose VP1 content was improved (VP1h/VP2 VLP). The expression, purity, and morphology of these two VLPs were characterized, and then their immunogenic properties were investigated and compared with those of the VLP containing VP2 alone (VP2 VLP) previously developed by our group. Furthermore, the location of the VP1 unique region in the VLPs was determined by using the immunogold electron microscopy (IGEM). Our experimental results show that the VP1h/VP2 VLP elicits a stronger neutralization against the HPV B19 than VP2 and VP1/VP2 VLPs, which implies that the increase of VP1 content significantly improves the level of neutralizing antibodies. In addition, the IGEM observations suggest that the unique region of VP1 may be located inside the recombinant VLP. The VLPs recombinantly expressed by our
system may serve as a promising candidate immunogen for HPV B19 vaccine development.
Two fluorescent probes, Y1-2 were synthesized from 2-acetonaphthone, 4-acetylbiphenyl, and phenyl hydrazine by Vilsmeier-Haack reaction and Knoevenagel condensation. Their recognition efficacies for ...N2H4 were tested by UV-visible absorption spectroscopy and fluorescence emission spectroscopy. The recognition mechanism were studies by density-functional theory calculations, and the effect of pH on N2H4 recognition was also studied. The results showed that the probe Y1-2 has high selectivity and a low detection limit for N2H4, and the recognition of N2H4 can be accomplished at physiological pH. The probes have had obvious aggregation-induced luminescence effect, large Stokes shift, high sensitivity, and can be successfully applied to live cell imaging.
One new species of the genus
Sinopoda
Jäger, 1999,
S. muyuensis
sp. nov.
(♂, ♀), is described and figured from the Shennongjia Forestry District, Hubei Province, China. In addition, the male of
...Sinopoda wuyiensis
Liu, 2021 is described for the first time from the Wuyishan National Nature Reserve, Fujian Province, China.
Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with ...locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population.
This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18–65 years with newly diagnosed high-risk non-metastatic stage III–IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3–4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing.
Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0–44·8; 389 alive at primary data cutoff Feb 28, 2023 and 366 94% had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% 95% CI 81–90 vs 76% 70–81; stratified hazard ratio 0·59 0·38–0·92; p=0·019). Grade 3–4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 33% vs 64 30%), leukopenia (54 26% vs 48 22%), and neutropenia (50 24% vs 46 21%). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3–4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group.
Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma.
National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center.
For the Chinese translation of the abstract see Supplementary Materials section.
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