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Abstract Negative pressure wound therapy with instillation and dwell time (NPWTi-d) is increasingly used for a diverse range of wounds. Meanwhile, the topical wound irrigation solution consisting of polyhexamethylene biguanide and betaine (PHMB-B) has shown efficacy in managing wound infections. However, the effectiveness of this solution as a topical instillation solution for NPWTi-d in patients with diabetic foot infections (DFIs) has not been thoroughly studied. The objective of this retrospective study was to evaluate the impact of using PHMB-B as the instillation solution during NPWTi-d on reducing bioburden and improving clinical outcomes in patients with DFIs. Between January 2017 and December 2022, a series of patients with DFIs received treatment with NPWTi-d, using either PHMB-B or normal saline as the instillation solution. Data collected retrospectively included demographic information, baseline wound characteristics, and treatment outcomes. The study included 61 patients in the PHMB-B group and 73 patients in the normal saline group, all diagnosed with DFIs. In comparison to patients treated with normal saline, patients with PHMB-B exhibited no significant differences in terms of wound bed preparation time (P = 0.5034), length of hospital stay (P = 0.6783), NPWTi-d application times (P = 0.1458), duration of systematic antimicrobial administration (P = 0.3567), or overall cost of hospitalization (P = 0.6713). The findings of the study suggest that the use of either PHMB-B or normal saline as an instillation solution in NPWTi-d for DFIs shows promise and effectiveness, yet no clinical distinction was observed between the two solutions.

Abstract The inflammatory response is a key factor affecting tissue regeneration. Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN‐SPD) is developed, where the first and second networks are formed by dynamic imine bonds and non‐dynamic photo‐crosslinked bonds respectively. The single network hydrogel before photo‐crosslinking exhibits excellent injectability and thus can be printed and photo‐crosslinked in situ to form double network hydrogels. DN‐SPD hydrogel has demonstrated desirable mechanical properties and tissue adhesion. More importantly, an “operando” comparison of hydrogels loaded with spermidine or diethylenetriamine (DETA), a sham molecule resembling spermidine, has shown similar physical properties, but quite different biological functions. Specifically, the outcomes of 3 sets of in vivo animal experiments demonstrate that DN‐SPD hydrogel can not only reduce inflammation caused by implanted exogenous biomaterials and reactive oxygen species but also promote the polarization of macrophages toward regenerative M2 phenotype, in comparison with DN‐DETA hydrogel. Moreover, the immunoregulation by spermidine can also translate into faster and more natural healing of both acute wounds and diabetic wounds. Hence, the local administration of spermidine affords a simple but elegant approach to attenuate foreign body reactions induced by exogenous biomaterials to treat chronic refractory wounds.

BackgroundPoor glycemic control with elevated levels of hemoglobin A1c (HbA1c) is associated with increased risk of cognitive impairment, with potentially varying effects between sexes. However, the causal impact of poor glycemic control on white matter brain aging in men and women is uncertain.MethodsWe used two nonoverlapping data sets from UK Biobank cohort: gene-outcome group (with neuroimaging data, (N = 15,193; males/females: 7,101/8,092)) and gene-exposure group (without neuroimaging data, (N = 279,011; males/females: 122,638/156,373)). HbA1c was considered the exposure and adjusted “brain age gap” (BAG) was calculated on fractional anisotropy (FA) obtained from brain imaging as the outcome, thereby representing the difference between predicted and chronological age. The causal effects of HbA1c on adjusted BAG were studied using the generalized inverse variance weighted (gen-IVW) and other sensitivity analysis methods, including Mendelian randomization (MR)-weighted median, MR-pleiotropy residual sum and outlier, MR-using mixture models, and leave-one-out analysis.ResultsWe found that for every 6.75 mmol/mol increase in HbA1c, there was an increase of 0.49 (95% CI = 0.24, 0.74; p-value = 1.30 × 10−4) years in adjusted BAG. Subgroup analyses by sex and age revealed significant causal effects of HbA1c on adjusted BAG, specifically among men aged 60–73 (p-value = 2.37 × 10−8).ConclusionPoor glycemic control has a significant causal effect on brain aging, and is most pronounced among older men aged 60–73 years, which provides insights between glycemic control and the susceptibility to age-related neurodegenerative diseases.

Abstract Background Lung adenocarcinoma (LUAD) has a high mortality rate. Ferroptosis is linked to tumor initiation and progression. Aims This study aims to develop prognostic models of ferroptosis‐related lncRNAs, evaluate the correlation between differentially expressed genes and tumor microenvironment, and identify prospective drugs for managing LUAD. Methods and Results In this study, transcriptomic and clinical data were downloaded from the TCGA database, and ferroptosis‐related genes were obtained from the FerrDb database. Through correlation analysis, Cox analysis, and the LASSO algorithm for constructing a prognostic model, we found that ferroptosis‐related lncRNA‐based gene signatures (FLncSig) had a strong prognostic predicting ability in the LUAD patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments reconfirmed that ferroptosis is related to receptor‐ligand activity, enzyme inhibitor activity, and the IL‐17 signaling pathway. Next, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE) algorithms, and pRRophetic were used to predict immunotherapy response and chemotherapy sensitivity. The IMvigor210 cohort was also used to validate the prognostic model. In the tumor microenvironment, Type_II_IFN_Response and HLA were found to be a group of low‐risk pathways, while MHC_class_I was a group of high‐risk pathways. Patients in the high‐risk subgroup had lower TIDE scores. Exclusion, MDSC, CAF, and TAMM2 were significantly and positively correlated with risk scores. In addition, we found 15 potential therapeutic drugs for LUAD. Finally, differential analysis of stemness index based on mRNA expression (mRNAsi) indicated that mRNAsi was correlated with gender, primary tumor (T), distant metastasis (M), and the tumor, node, and metastasis (TNM) stage in LUAD patients. Conclusions In conclusion, the prognostic model based on FLncSig can alleviate the difficulty in predicting the prognosis and immunotherapy of LUAD patients. The identified FLncSig and the screened drugs exhibit potential for clinical application and provide references for the treatment of LUAD.

Development of a vaccine for human cytomegalovirus (hCMV) is critical because of the severe consequences of infection in congenitally infected newborns and immunocompromised patients. The assessment of hCMV-neutralizing antibody activity is crucial for vaccine development. This study evaluated a RT-qPCR assay targeting the immediate-early gene transcript of hCMV for determining microneutralizing antibody activity. The assay was evaluated for sensitivity, specificity, and precision using endotheliotropic clinical isolate VR1814 that infects fibroblasts, epithelial, and endothelial cells. The RT-qPCR-based neutralization assay was compared with an immunostaining-based neutralization assay using virions present in hCMV-positive urine, saliva, and breast-milk samples. Our results showed that hCMV replication was detectable at 20 h post-infection with a limit of detection of 1 infectious units (IU)/reaction. The RT-qPCR assay had a dynamic range of 1 to 1.0 × 104 IU/reaction, with coefficients of variation ranging from 0.94% to 15.08%. The RT-qPCR results were in high agreement with the immunostaining assay for hCMV-antibody neutralization assessment. Overall, the RT-qPCR neutralization assay is a reliable, rapid, efficient, and sensitive alternative method for evaluating hCMV-neutralizing activity in vitro.

Background To address the lack of mental health practitioners in developing countries, the current study explored the feasibility of a newly developed self-guided digital intervention program TEA (training for emotional adaptation) in alleviating depressive and anxiety symptoms, as one of a few studies which adapted from theoretical models with effective intervention techniques. Methods The first part of this study involved 11 professional mental health practitioners giving feedback on the feasibility of the TEA; while the second part involved a mixed-method single-arm study with 32 participants recruited online, who went through the seven intervention sessions within 14 days. The questionnaires were collected before, after, 14 days after, and 30 days after intervention. Additionally, 10 participants were invited to semi-structured interviews regarding their suggestions. Results Practitioners thought that the TEA showed high professionalism (8.91/10) and is suitable for treating emotional symptoms (8.09/10). The generalized estimating equation model showed that the TEA significantly reduced participants' depressive and anxiety symptoms, while the effects of the intervention remained 30 days post intervention (Cohen's d > 1). Thematic analysis revealed three main themes about future improvement, including content improvement, interaction improvement, and bug-fixing. Conclusions To address the current needs for digital mental health intervention programs to account for the insufficient availability of mental health services in China, the current study provides preliminary evidence of the effectiveness of TEA, with the potential to address the urgent need for remote mental health services. Trial registration The study was registered at the Chinese Clinical Trial Register (ChiCTR), with number [ChiCTR2200065944].

Genetic instability can be caused by external factors and may also be associated with intracellular damage. At the same time, there is a large body of research investigating the mechanisms by which genetic instability occurs and demonstrating the relationship between genomic stability and tumors. Nowadays, tumorigenesis development is one of the hottest research areas. It is a vital factor affecting tumor treatment. Mechanisms of genomic stability and tumorigenesis development are relatively complex. Researchers have been working on these aspects of research. To explore the research progress of genomic stability and tumorigenesis, development, and treatment, the authors searched PubMed with the keywords ''genome instability'' ''chromosome instability'' ''DNA damage'' ''tumor spread'' and ''cancer treatment''. This extracts the information relevant to this study. Results: This review introduces genomic stability, drivers of tumor development, tumor cell characteristics, tumor metastasis, and tumor treatment. Among them, immunotherapy is more important in tumor treatment, which can effectively inhibit tumor metastasis and kill tumor cells. Breakthroughs in tumorigenesis development studies and discoveries in tumor metastasis will provide new therapeutic techniques. New tumor treatment methods can effectively prevent tumor metastasis and improve the cure rate of tumors.

This paper addresses the spatial pattern of urban biomedicine innovation networks by separately using four scales, i.e., the national scale, interregional scale, urban agglomeration scale, and provincial scale, on the basis of Chinese biomedicine patent data from the incoPat global patent database (GPD) (2001–2020) and using the method of social network analysis (SNA). Through the research, it is found that (1) on the national scale, the Chinese biomedicine innovation network becomes denser from west to the east as its complexity continuously increases. Its spatial structure takes the form of a radial network pattern with Beijing and Shanghai as its centers. The COVID-19 pandemic has not had an obvious negative impact on this network at present. (2) On the interregional scale, the strength of interregional network ties is greater than that of intraregional network ties. The eastern, central and western biomedicine innovation networks appear to be heterogeneous networks with regional central cities as the cores. (3) At the urban agglomeration scale, the strength of intraurban-agglomeration network ties is greater than that of interurban-agglomeration network ties. The three major urban agglomerations have formed radial spatial patterns with central cities as the hubs. (4) At the provincial scale, the intraprovincial networks have poor connectivity and low internal ties strength, which manifest as core-periphery structures with the provincial capitals as centers. Our research conclusion helps to clarify the current accumulation of technology and offer guidance for the development of China's biomedicine industry.

RationaleFructose-1,6-bisphosphatase (FBP1) is a tumor suppressor and a key enzyme negatively regulating Warburg effect in cancer. However, regulation of FBP1 protein expression and its exact role in prostate cancer (PCa) is largely unclear. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumor suppressor genes in human PCa. However, the role of PTEN loss in aberrant Warburg effect in cancer remains poorly understood.MethodsExpression of PTEN and FBP1 was analyzed in several PCa cell lines and prostate tumor tissues in mice. Western blot (WB) and RT-PCR approaches were used to examine how PTEN regulates FBP1 expression. Co-immunoprecipitation (co-IP) and in vivo ubiquitination assays were used to define the regulatory mechanisms. A PCa xenograft model was employed to determine the impact of PTEN regulation of FBP1 on PCa growth in vivo.ResultWe demonstrated that in a manner dependent of PI3K/AKT signal pathway PTEN regulated FBP1 expression in various PCa cell lines and tumors in mice. We confirmed that this regulation took place at the protein level and was mediated by SKP2 E3 ubiquitin ligase. Mechanistically, we showed that serine 271 phosphorylation of FBP1 by cyclin-dependent kinases (CDKs) was essential for SKP2-mediated degradation of FBP1 protein induced by PTEN loss. Most importantly, we further showed that loss of PTEN expression enhanced Warburg effect and PCa growth in mice in a manner dependent, at least partially on FBP1 protein degradation.ConclusionsOur results reveal a novel tumor-suppressive feature of PTEN in restraining FBP1 degradation and the Warburg effect. These results also suggest that prohibiting FBP1 protein degradation could be a viable therapeutic strategy for PTEN-deficient PCa.

Since the outbreak of Coronavirus Disease 2019 (COVID-19), the Chinese government has taken a number of measures to effectively control the pandemic. By the end of 2021, China achieved a full vaccination rate higher than 85%. The Chinese Plan provides an important model for the global fight against COVID-19. Internet search reflects the public's attention toward and potential demand for a particular thing. Research on the spatiotemporal characteristics of online attention to vaccines can determine the spatiotemporal distribution of vaccine demand in China and provides a basis for global public health policy making. This study analyzes the spatiotemporal characteristics of online attention to vaccines and their influencing factors in 31 provinces/municipalities in mainland China with Baidu Index as the data source by using geographic concentration index, coefficient of variation, GeoDetector, and other methods. The following findings are presented. First, online attention to vaccines showed an overall upward trend in China since 2011, especially after 2016. Significant seasonal differences and an unbalanced monthly distribution were observed. Second, there was an obvious geographical imbalance in online attention to vaccines among the provinces/municipalities, generally exhibiting a spatial pattern of “high in the east and low in the west.” Low aggregation and obvious spatial dispersion among the provinces/municipalities were also observed. The geographic distribution of hot and cold spots of online attention to vaccines has clear boundaries. The hot spots are mainly distributed in the central-eastern provinces and the cold spots are in the western provinces. Third, the spatiotemporal differences in online attention to vaccines are the combined result of socioeconomic level, socio-demographic characteristics, and disease control level.

Phytoplankton play a critical role in marine food webs and biogeochemical cycles, and their abundance must be monitored to prevent disasters and improve the marine environment. Although existing algorithms for automatic phytoplankton identification at the image level are available, there are currently no video-level algorithms. This lack of datasets is a significant obstacle to the development of video-level automatic identification algorithms for phytoplankton observations. Deep learning-based algorithms, in particular, require high-quality datasets to achieve optimal results. To address this issue, we propose the PMOT2023 (Phytoplankton Multi-Object Tracking), a multi-video tracking dataset based on 48,000 micrographs captured by in situ observation devices. The dataset comprises 21 classes of phytoplankton and can aid in the development of advanced video-level identification methods. Multi-object tracking algorithms can detect, classify, count, and estimate phytoplankton density. As a video-level automatic identification algorithm, multi-object tracking addresses trajectory tracking, concentration estimation, and other requirements in original phytoplankton observation, helping to prevent marine ecological disasters. Additionally, the PMOT2023 dataset will serve as a benchmark to evaluate the performance of future phytoplankton identification models and provide a foundation for further research on automatic phytoplankton identification algorithms.

Wastewater-based surveillance is emerging as an important tool for the COVID-19 pandemic trending. Current methods of wastewater collection, such as grab and auto-composite sampling, have drawbacks that impede effective surveillance, especially from small catchments with limited accessibility. Passive samplers, which are more cost-effective and require fewer resources to process, are promising candidates for monitoring wastewater for SARS-CoV-2. Here, we compared traditional auto sampling with passive sampling for SARS-CoV-2 detection in wastewater. A torpedo-style 3D-printed passive sampler device containing both cotton swabs and electronegative filter membranes was used. Between April and June 2021, fifteen passive samplers were placed at a local hospital’s wastewater outflow alongside an autosampler. Reverse transcription and quantitative polymerase chain reaction (RT-qPCR) was used to detect SARS-CoV-2 in the samples after processing and RNA extraction. The swab and membrane of the passive sampler showed similar detection rates and cycle threshold (Ct) values for SARS-CoV-2 RNA for the N1 and N2 gene targets. The passive method performed as well as the grab/auto sampling, with no significant differences between N1 and N2 Ct values. There were discrepant results on two days with negative grab/auto samples and positive passive samples, which might be related to the longer duration of passive sampling in the study. Overall, the passive sampler was rapid, reliable, and cost-effective, and could be used as an alternative sampling method for the detection of SARS-CoV-2 in wastewater.

As it is well known, muscle atrophy is a process in which protein degradation increases and protein synthesis decreases. This process is regulated by a variety of links. Among them, microRNAs play an essential role in this process, which has attracted widespread attention. In this paper, we find that miR-27b-3p and Cbl-b genes are significantly differentially expressed in the induced atrophy model. The dual-luciferase experiment and Western blot analysis confirmed that miR-27b-3p could regulate the expression of Cbl-b. In C2C12-differentiated myotubes, the overexpression of the Cbl-b gene showed that Cbl-b could upregulate the expression of MuRF-1 and Atrogin-1, which are related marker genes of muscle atrophy, at both the mRNA and protein levels, indicating that the Cbl-b gene can specifically affect muscle atrophy. The knockdown of the Cbl-b gene after C2C12-differentiated myotubes induced atrophy treatment can downregulate the expression of muscle-atrophy-related genes, indicating that manual intervention to downregulate the expression of Cbl-b has a certain alleviating effect on muscle atrophy. These data suggest that miR-27b-3p can regulate the expression of the Cbl-b gene and then exert a particular influence on muscle atrophy through the Cbl-b gene.

Mounting evidence suggests that solids are a reliable matrix for SARS-CoV-2 detection in wastewater, yet studies comparing solids-based methods and common concentration methods using the liquid fraction remain limited. In this study, we developed and optimized a method for SARS-CoV-2 detection in wastewater using moderate-speed centrifuged solids and evaluated it against an ultrafiltration reference method. SARS-CoV-2 was quantified in samples from 12 wastewater treatment plants from Alberta, Canada, using RT-qPCR targeting the N2 and E genes. PCR inhibition was examined by spiking salmon DNA. The effects of using different amounts of solids, adjusting the sample pH to 9.6–10, and modifying the elution volume at the final step of RNA extraction were evaluated. SARS-CoV-2 detection rate in solids from 20 mL of wastewater showed no statistically significant difference compared to the ultrafiltration method (97/139 versus 90/139, p = 0.26, McNemar’s mid-p test). The optimized wastewater solids-based method had a significantly lower rate of samples with PCR inhibition versus ultrafiltration (3% versus 9.5%, p = 0.014, Chi-square test). Our optimized moderate-speed centrifuged solids-based method had similar sensitivity when compared to the ultrafiltration reference method but had the added advantages of lower costs, fewer processing steps, and a shorter turnaround time.

An equivalent circuit model of double hexagonal loops frequency selective surface (FSS) was established. The formulas of LC parameters were proposed with equivalent repetition period. The reflection frequency, transmission frequency, and the location of first modal interaction null were simulated, and the results showed a good agreement in full-wave simulation result. On this basis, an ultra-wideband composite absorbing material (CAM) was proposed, and its equivalent circuit model was also established. A sample was fabricated and measured to verify the validity of the model. The results showed a good ultra-wideband absorbing performance in the range of 1.9–8.9 GHz.

Based on the purpose of proactive anti-reconnaissance, the essential characteristics of several typical pulse repetition interval (PRI) sorting algorithms were analysed and the feasibility of counter-deinterleaving was discussed. A method for disturbing arrival time sequence by using interference pulse was proposed, which changes the statistical properties of the radar PRI to disturb the deinterleaving results. The simulation results show that the pulse jamming method proposed in this paper can influence PRI sorting process effectively, which let signal processer make a misjudgment on PRI pattern of radar.

Aim: To explore the effect of polyhexanidine (PHMB) on the biofilm formation of Pseudomonas aeruginosa and Staphylococcus aureus in vitro. To investigate the effect of polyhexanidine (PHMB) on mature P.aeruginosa and S.aureus biofilms in vitro. Method: 1. Strain isolation and culture: Three strains each of P.aeruginosa and S.aureus isolated and cultured from the wounds of burn and skin wound repair surgery patients in the First Hospital of Jilin University in 2019 were collected and screened for dominant membrane-forming strains. The experiment was divided into PHMB experimental group and blank control group. 2.0.2%PHMB configuration: The PHMB and pure water are configured with 0.2% concentration; 3. Establishment of mature bacterial biofilm. 4.0.2%PHMB on mature bacterial biofilm.5.0.2%PHMB on the formation of bacterial biofilm. Results / Discussion: 1. Under confocal laser microscope, after 0.2%PHMB was applied to mature P.aeruginosa and S.aureus biofilms, the bacterial density decreased significantly and the rate of dead bacteria increased significantly. 2. Under scanning electron microscope, it was observed that after 0.2%PHMB was applied to mature P.aeruginosa and S.aureus biofilms, the density of the bacteria decreased, the morphology of the bacteria was significantly deformed or cracked, and the filamentous structure between the bacteria was broken. 3.0.2%PHMB was co-cultured with P.aeruginosa and S.aureus, no typical bacterial biofilm formation was observed in the culture dishes of the two types of bacteria under laser confocal microscope. Conclusion: P.aeruginosa and S.aureus isolated from burn patients can form a typical and firm bacterial biofilm in vitro. 2.0.2%PHMB can continuously destroy the mature P.aeruginosa and S.aureus biofilms within 12 hours. 3.0.2%PHMB can significantly affect the biofilm formation of P.aeruginosa and S.aureus. [ABSTRACT FROM AUTHOR]

We retrospectively assessed outcomes after treating severe contractures of the first web space from burns with the reverse posterior interosseous flaps (RPIF). Twelve consecutive patients (ages 18-58 years) with burns from 10% to 70% (mean, 30.1%) total body surface area and severe contractures of the first web space of the hand (initial thumb to index angles from 10° to 35° [mean, 23 ]) underwent contracture release using the RPIF. Seventeen RPIFs were used, with sizes from 9 cm x 6 cm to 14 cm x 10 cm (mean area, 83.6 cm²). The patients were followed for 5-26 months. All flaps survived completely, rapidly adapted to the recipient beds, and achieved good color and texture harmony. No early complications occurred. Fifteen donor sites were closed with skin grafts. Two donor sites were closed by direct suture. No paralysis of the posterior interosseous nerve was observed in these cases. At last follow-up the mean thumb to index angle was 78°, increasing the web length 260%. All patients regained fundamental hand functions. The RPIF is reliable and safe for releasing severe contractures of the first web space of the hand after burn, with distinct advantages over currently used alternative methods. [ABSTRACT FROM AUTHOR]