Analytical and clinical validation of multiplex droplet digital PCR assay for detecting pathogenic fungal infection in lungs.

Pulmonary invasive fungal infection in immunocompromised hosts is difficult to diagnose, and current tools for diagnosis or monitoring of response to antifungal treatments have inherent limitations. Droplet digital PCR (ddPCR) has emerged as a promising tool for pulmonary pathogen detection with high sensitivity. This study presents a novel ddPCR panel for rapid and sensitive identification of pulmonary fungal pathogens. First, a ddPCR method for detecting three fungal genera, including Pneumocystis, Aspergillus, and Cryptococcus, was established and evaluated. Then, the clinical validation performance of ddPCR was compared with that of qPCR using 170 specimens, and the 6 specimens with inconsistent results were further verified by metagenomics next-generation sequencing, which yielded results consistent with the ddPCR findings. Finally, the area under the ROC curve (AUC) was used to evaluate the efficiency of ddPCR. While the qPCR identified 16 (9.41%) cases of Aspergillus and 6 (3.53%) cases of Pneumocystis, ddPCR detected 20 (11.76%) Aspergillus cases and 8 (4.71%) Pneumocystis cases. The AUC for Aspergillus, Cryptococcus, and Pneumocystis was 0.974, 0.998, and 0.975, respectively. These findings demonstrated that the ddPCR assay is a highly sensitive method for identifying pathogens responsible for invasive fungal pulmonary infections, and is a promising tool for early diagnosis. .

Nucleosome Dynamics Derived at the Single-Molecule Level Bridges Its Structures and Functions.

Nucleosome, the building block of chromatin, plays pivotal roles in all DNA-related processes. While cryogenic-electron microscopy (cryo-EM) has significantly advanced our understanding of nucleosome structures, the emerging field of single-molecule force spectroscopy is illuminating their dynamic properties. This technique is crucial for revealing how nucleosome behavior is influenced by chaperones, remodelers, histone variants, and post-translational modifications, particularly in their folding and unfolding mechanisms under tension. Such insights are vital for deciphering the complex interplay in nucleosome assembly and structural regulation, highlighting the nucleosome's versatility in response to DNA activities. In this Perspective, we aim to consolidate the latest advancements in nucleosome dynamics, with a special focus on the revelations brought forth by single-molecule manipulation. Our objective is to highlight the insights gained from studying nucleosome dynamics through this innovative approach, emphasizing the transformative impact of single-molecule manipulation techniques in the field of chromatin research.

Hereditary hemochromatosis caused by a C282Y/H63D mutation in the HFE gene: A case report.

Hereditary hemochromatosis (HH) is a disease characterized by disordered iron metabolism. It often involves mutations of the HFE gene, which encodes the homeostatic iron regulator protein (HFE), as well as mutations affecting hepcidin antimicrobial peptide, hemojuvelin, or transferrin receptor 2. Historically, HH has been observed primarily in European and European diaspora populations, while classical HH is rare in Asian populations, including in China. In this article, we report a rare case of HH in a Chinese man that could be attributed to a heterozygous C282Y/H63D HFE mutation. Based on clinical examination, liver biopsy, and genetic testing results, the patient was diagnosed with HH. Clinical signs and symptoms and serum iron-related test results were recorded for a period of two years after the patient began treatment. Over this observation period, the patient was subjected to 25 phlebotomies (accounting for a total blood loss of 10.2 L). His serum ferritin levels decreased from 1550 µg/L to 454 µg/L, his serum iron concentration decreased from 40 µmol/L to 24.6 µmol/L, and his transferrin saturation decreased from 97.5% to 55.1%. Early diagnosis is essential for patients with HH to obtain good outcomes. Regular phlebotomy after diagnosis can improve HH symptoms and delay HH disease progression.

Microforceps-Assisted Transscleral Fixation of Intraocular Lens.

PURPOSE: We present a novel technique for intraocular lens (IOL) fixation. The technique can be used on single-piece acrylic IOLs and can manage the patients who are either aphakia or with a dislocated IOL. METHODS: One end of Gore-Tex suture is tied into the optic-haptic junction of the IOL. Another end is fixated in the scleral wall. The single sclerotomy and double sclerotomies settings can be applied to different situations. RESULTS: Twelve eyes received this procedure. After a follow-up period of up to 20 months, the IOLs were well centered. CONCLUSION: The technique is a reliable method for scleral fixation of IOLs, which can be applied on the widely used single-piece acrylic IOLs. In our experience, it is reproducible and rarely cause complications.

Recent progress and outlooks in rhodamine-based fluorescent probes for detection and imaging of reactive oxygen, nitrogen, and sulfur species.

Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) serve as vital mediators essential for preserving intracellular redox homeostasis within the human body, thereby possessing significant implications across physiological and pathological domains. Nevertheless, deviations from normal levels of ROS, RNS, and RSS disturb redox homeostasis, leading to detrimental consequences that compromise bodily integrity. This disruption is closely linked to the onset of various human diseases, thereby posing a substantial threat to human health and survival. Small-molecule fluorescent probes exhibit considerable potential as analytical instruments for the monitoring of ROS, RNS, and RSS due to their exceptional sensitivity and selectivity, operational simplicity, non-invasiveness, localization capabilities, and ability to facilitate in situ optical signal generation for real-time dynamic analyte monitoring. Due to their distinctive transition from their spirocyclic form (non-fluorescent) to their ring-opened form (fluorescent), along with their exceptional light stability, broad wavelength range, high fluorescence quantum yield, and high extinction coefficient, rhodamine fluorophores have been extensively employed in the development of fluorescent probes. This review primarily concentrates on the investigation of fluorescent probes utilizing rhodamine dyes for ROS, RNS, and RSS detection from the perspective of different response groups since 2016. The scope of this review encompasses the design of probe structures, elucidation of response mechanisms, and exploration of biological applications.

Potentials as biomarker and therapeutic target of upregulated long non-coding RNA HLA-F antisense RNA 1 in hepatitis B virus-associated hepatocellular carcinoma.

The tissue-specific characteristics have encouraged researchers to identify organ-specific lncRNAs as disease biomarkers. This study aimed to identify the clinical and functional roles of long non-coding RNA HLA-F antisense RNA 1 (HLA-F-AS1) in hepatitis B virus (HBV)-hepatocellular carcinoma (HCC). A total of 121 HBV-HCC, 81 chronic hepatitis B (CHB), and 85 normal liver tissues were evaluated in this study. Real-time quantitative PCR assay was used to evaluate the RNA expression levels. Performance in diagnosis was compared between alpha fetoprotein (AFP) and HLA-F-AS1 using Receiver Operating Characteristic (ROC) curves. Performance in post-hepatectomy prognosis with high or low HLA-F-AS1 was compared using Kaplan-Meier curves. Multi-variable analysis was used to determine the informative predictors. Downstream miRNAs for HLA-F-AS1 were predicted and miR-128-3p was confirmed by luciferase reporter assay and RNA pull-down assay. In vitro functional analysis was performed by MTS reagent for cell proliferation and transwell assay for cell migration. HLA-F-AS1 levels were significantly increased in the HBV-HCC compared to normal healthy tissue and CHB tissues. HLA-F-AS1 exhibited a well potential in making a distinction between HBV-HCC and health, as well as HBV-HCC and CHB. The survival analysis revealed that patients with high levels of HLA-F-AS1 tend to shorter overall survival times. The best prognostic performance was achieved by HLA-F-AS1 after multi-variable analysis (HR 2.290, 95% CI 1.191-4.403, p = 0.013). Functional analysis showed that HLA-F-AS1 promoted cell proliferation and migration via miR-128-3p. Up-regulation of HLA-F-AS1 could serve as a promising diagnostic and prognostic marker for HBV-HCC after surgery, maybe useful in the management of HBV-HCC patients. HLA-F-AS1 can promote the progression of HBV-HCC, may be useful in the targeting treatment of HBV-HCC patients.

Application of computer vision and deep learning models to automatically classify medically important mosquitoes in North Borneo, Malaysia.

Mosquito-borne diseases have emerged in North Borneo in Malaysia due to rapid changes in the forest landscape, and mosquito surveillance is key to understanding disease transmission. However, surveillance programmes involving sampling and taxonomic identification require well-trained personnel, are time-consuming and labour-intensive. In this study, we aim to use a deep leaning model (DL) to develop an application capable of automatically detecting mosquito vectors collected from urban and suburban areas in North Borneo, Malaysia. Specifically, a DL model called MobileNetV2 was developed using a total of 4880 images of Aedes aegypti, Aedes albopictus and Culex quinquefasciatus mosquitoes, which are widely distributed in Malaysia. More importantly, the model was deployed as an application that can be used in the field. The model was fine-tuned with hyperparameters of learning rate 0.0001, 0.0005, 0.001, 0.01 and the performance of the model was tested for accuracy, precision, recall and F1 score. Inference time was also considered during development to assess the feasibility of the model as an app in the real world. The model showed an accuracy of at least 97%, a precision of 96% and a recall of 97% on the test set. When used as an app in the field to detect mosquitoes with the elements of different background environments, the model was able to achieve an accuracy of 76% with an inference time of 47.33 ms. Our result demonstrates the practicality of computer vision and DL in the real world of vector and pest surveillance programmes. In the future, more image data and robust DL architecture can be explored to improve the prediction result.

Noninvasive Artificial Intelligence System for Early Predicting Residual Cancer Burden during Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

Octave soliton microcombs in lithium niobate microresonators.

Soliton microcombs are regarded as an ideal platform for applications such as optical communications, optical sensing, low-noise microwave sources, optical atomic clocks, and frequency synthesizers. Many of these applications require a broad comb spectrum that covers an octave, essential for implementing the f - 2f self-referencing techniques. In this work, we have successfully generated an octave-spanning soliton microcomb based on a z-cut thin-film lithium niobate (TFLN) microresonator. This achievement is realized under on-chip optical pumping at 340 mW and through extensive research into the broadening of dual dispersive waves (DWs). Furthermore, the repetition rate of the octave soliton microcomb is accurately measured using an electro-optic comb generated by an x-cut TFLN racetrack microresonator. Our results represent a crucial step toward the realization of practical, integrated, and fully stabilized soliton microcomb systems based on TFLN.

Neuron-targeted liposomal coenzyme Q10 attenuates neuronal ferroptosis after subarachnoid hemorrhage by activating the ferroptosis suppressor protein 1/coenzyme Q10 system.

Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. SAH disrupts the blood‒brain barrier, leading to the release of iron ions from blood within the subarachnoid space, subsequently inducing neuronal ferroptosis. A recently discovered protein, known as ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10 by introducing the neuron-targeting peptide Tet1 onto the surface of liposomal CoQ10. Our objective was to determine whether this formulation could activate the FSP1 system and subsequently inhibit neuronal ferroptosis. Our findings revealed that neuron-targeted liposomal CoQ10 effectively localized to neurons at the lesion site after SAH. Furthermore, it facilitated the upregulation of FSP1, reduced the accumulation of malondialdehyde and reactive oxygen species, inhibited neuronal ferroptosis, and exerted neuroprotective effects both in vitro and in vivo. Our study provides evidence that supplementation with CoQ10 can effectively activate the FSP1 system. Additionally, we developed a neuron-targeted liposomal CoQ10 formulation that can be selectively delivered to neurons at the site of SAH. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH. STATEMENT OF SIGNIFICANCE: Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. Ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10. We find that it effectively localized to neurons at the lesion site after SAH and activated the FSP1/CoQ10 system. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH and other central nervous system diseases characterized by disruption of the blood-brain barrier.

Photodynamic Therapy Combined with Liquid Nitrogen Cryotherapy and Curettage for the Treatment of Recalcitrant Periungual and Subungual Warts: Clinical Experience and Literature Review.

Warts are caused by human papillomavirus (HPV) infection and can involve multiple parts of skin and mucosa, of which periungual and subungual warts are the most difficult to treat. Periungual or subungual wart is verruca vulgaris growing around or under the fingernail, destroying and deforming the nail and nail bed. Currently, liquid nitrogen cryotherapy and CO2 laser are often used for the treatment. Clinically, few doctors routinely use photodynamic therapy (PDT) to treat viral warts. We used PDT combined with liquid nitrogen cryotherapy and curettage to successfully treat a case of intractable periungual and subungual warts.

The effects of live streamer's expertise and entertainment on the viewers' purchase and follow intentions.

This study explores the impact of two characteristics of streamers-expertise and entertainment-on viewers' purchase intention and follow intention in live-streaming e-commerce, with a specific focus on viewers' trust and flow experience as two mediators and viewers' optimal stimulation level as a moderator. We implemented a methodological approach where participants were randomly directed to enter a live broadcast room and watch a 10-min live session before engaging in a structured questionnaire. 399 valid questionnaires were collected from the participants. These 399 valid questionnaires were subsequently utilized to validate the research model using structural equation modeling (SEM). The results suggest that streamer expertise and entertainment enhance viewers' trust and flow experience, which then leads to an increase in their intention to make a purchase and continue following the streamer. Furthermore, the viewers' optimal stimulation level acts as a moderator in the connections between streamer characteristics and viewers' trust and flow experience, suggesting that individual differences among consumers affect how they respond to streamer characteristics. From the dual perspectives of the streamer and the viewer, this study provides a more comprehensive theoretical perspective on customer behavior in live streaming commerce by not only focusing on consumers' short-term, transactional behavior inclinations but also long-term, relational behavior intentions.

Water masses influence the variation of microbial communities in the Yangtze River Estuary and its adjacent waters.

The Yangtze River estuary (YRE) are strongly influenced by the Kuroshio and terrigenous input from rivers, leading to the formation of distinct water masses, however, there remains a limited understanding of the full extent of this influence. Here the variation of water masses and bacterial communities of 58 seawater samples from the YRE and its adjacent waters were investigated. Our findings suggested that there were 5 water masses in the studied area: Black stream (BS), coastal water in the East China Sea (CW), nearshore mixed water (NM), mixed water in the middle and deep layers of the East China Sea (MM), and deep water blocks in the middle of the East China Sea (DM). The CW mass harbors the highest alpha diversity across all layers, whereas the NM mass exhibits higher diversity in the surface layer but lower in the middle layers. Proteobacteria was the most abundant taxa in all water masses, apart from that, in the surface layer masses, Cyanobacterium, Bacteroidota, and Actinobacteriota were the highest proportion in CW, while Bacteroidota and Actinobacteriota were the highest proportion in NM and BS; in the middle layer, Bacteroidota and Actinobacteriota were dominant phylum in CW and BS masses, but Cyanobacterium was main phylum in NM mass; in the bottom layer, Bacteroidota and Actinobacteriota were the dominant phylum in CW, while Marininimicrobia was the dominated phylum in DM and MM masses. Network analysis suggests water masses have obvious influence on community topological characteristics, moreover, community assembly across masses also differ greatly. Taken together, these results emphasized the significant impact of water masses on the bacterial composition, topological characteristics and assembly process, which may provide a theoretical foundation for predicting alterations in microbial communities within estuarine ecosystems under the influence of water masses.

Construction of an Escherichia coli chassis for efficient biosynthesis of human-like N-linked glycoproteins.

The production of N-linked glycoproteins in genetically engineered Escherichia coli holds significant potential for reducing costs, streamlining bioprocesses, and enhancing customization. However, the construction of a stable and low-cost microbial cell factory for the efficient production of humanized N-glycosylated recombinant proteins remains a formidable challenge. In this study, we developed a glyco-engineered E. coli chassis to produce N-glycosylated proteins with the human-like glycan Gal-ß-1,4-GlcNAc-ß-1,3-Gal-ß-1,3-GlcNAc-, containing the human glycoform Gal-ß-1,4-GlcNAc-ß-1,3-. Our initial efforts were to replace various loci in the genome of the E. coli XL1-Blue strain with oligosaccharyltransferase PglB and the glycosyltransferases LsgCDEF to construct the E. coli chassis. In addition, we systematically optimized the promoter regions in the genome to regulate transcription levels. Subsequently, utilizing a plasmid carrying the target protein, we have successfully obtained N-glycosylated proteins with 100% tetrasaccharide modification at a yield of approximately 320 mg/L. Furthermore, we constructed the metabolic pathway for sialylation using a plasmid containing a dual-expression cassette of the target protein and CMP-sialic acid synthesis in the tetrasaccharide chassis cell, resulting in a 40% efficiency of terminal α-2,3- sialylation and a production of 65 mg/L of homogeneously sialylated glycoproteins in flasks. Our findings pave the way for further exploration of producing different linkages (α-2,3/α-2,6/α-2,8) of sialylated human-like N-glycoproteins in the periplasm of the plug-and-play E. coli chassis, laying a strong foundation for industrial-scale production.

Tiam1-mediated maladaptive plasticity underlying morphine tolerance and hyperalgesia.

Opioid pain medications, such as morphine, remain the mainstay for treating severe and chronic pain. Prolonged morphine use, however, triggers analgesic tolerance and hyperalgesia (OIH), which can last for a long period after morphine withdrawal. How morphine induces these detrimental side effects remains unclear. Here, we show that morphine tolerance and OIH are mediated by Tiam1-coordinated synaptic structural and functional plasticity in the spinal nociceptive network. Tiam1 is a Rac1 GTPase guanine nucleotide exchange factor (GEF) that promotes excitatory synaptogenesis by modulating actin cytoskeletal dynamics. We found that prolonged morphine treatment activated Tiam1 in the spinal dorsal horn and Tiam1 ablation from spinal neurons eliminated morphine antinociceptive tolerance and OIH. At the same time, the pharmacological blockade of Tiam1-Rac1 signaling prevented the development and reserved the established tolerance and OIH. Prolonged morphine treatment increased dendritic spine density and synaptic NMDA receptor (NMDAR) activity in spinal dorsal horn neurons, both of which required Tiam1. Furthermore, co-administration of the Tiam1 signaling inhibitor NSC23766 was sufficient to abrogate morphine tolerance in chronic pain management. These findings identify Tiam1-mediated maladaptive plasticity in the spinal nociceptive network as an underlying cause for the development and maintenance of morphine tolerance and OIH and provide a promising therapeutic target to reduce tolerance and prolong morphine use in chronic pain management.

Predictive value of free triiodothyronine to free thyroxine ratio on contrast-associated acute kidney injury and poor prognosis in euthyroid patients after percutaneous coronary intervention.

PURPOSE: The purpose of the study was to explore the predictive value of free triiodothyronine to free thyroxine ratio (FT3/FT4) on contrast-associated acute kidney injury (CA-AKI) and poor prognosis in euthyroid patients after percutaneous coronary intervention (PCI). METHODS: The present study included 3,116 euthyroid patients who underwent elective PCI. The main outcome was CA-AKI, and the secondary outcome was long-term mortality. All patients were divided into three groups according to the tertiles of FT3/FT4 levels. RESULTS: During hospitalization, a total of 160 cases (5.1%) of CA-AKI occurred. Restricted cubic spline (RCS) analysis indicated a linear and negative relationship between FT3/FT4 and CA-AKI risk (P for nonlinearity = 0.2621). Besides, the fully-adjusted logistic regression model revealed that patients in tertile 3 (low FT3/FT4 group) had 1.82 times [odds ratio (OR): 1.82, 95% confidence interval (CI): 1.13-3.02, P = 0.016] as high as the risk of CA-AKI than those in tertile 1 (high FT3/FT4 group). Similarly, patients in tertile 3 were observed to have a higher incidence of long-term mortality [fully-adjusted hazard ratio (HR): 1.58, 95% CI: 1.07-2.32, P = 0.021]. Similarly, the Kaplan-Meier curves displayed significant differences in long-term mortality among the three groups (log-rank test, P < 0.001). CONCLUSION: In euthyroid patients undergoing elective PCI, low levels of FT3/FT4 were independently associated with an increased risk of CA-AKI and long-term mortality. Routine evaluation of FT3/FT4 may aid in risk stratification and guide treatment decisions within this particular patient group.

Effective evaluations of community nursing on rehabilitation for stroke survivors: A meta-analysis.

BACKGROUND: Long-term rehabilitation of stroke survivors is often difficult and new tools to improve quality of life should be proposed. Community nursing can be a cost-effective tool to positively impact the lives of stroke survivors. This meta-analysis aimed to comprehensively evaluate the effects of community nursing on rehabilitation for stroke survivors. METHODS: The Cochrane Library, PubMed, Web of Science, CINAHL Plus, Embase, PEDro, China Knowledge Resource Integrated Database (CNKI), WANFANG, and WEIPU databases were comprehensively searched from their inception to April 18, 2023. The revised Cochrane risk-of-bias tool for RCTs(RoB 2 tool) was used to assess the quality of the included studies. Meta-analysis was conducted using the Stata 12.0 software package and Review Manager v5.3 software. RESULTS: A total of 25 randomized controlled trials with 2537 participants were included in the meta-analysis. Compared with the control group, community nursing combined with routine nursing had a significantly superior effect on the Barthel Index(BI), Fugl-Meyer(FMA), National Institutes of Health Stroke Scale(NIHSS), Self-rating Anxiety Scale(SAS), and Self-rating Depression Scale(SDS) scores for stroke survivors (BI: MD: 18.48, 95 % CI [16.87, 20.08], P < 0.00001; FMA: MD: 12.61, 95 % CI [10.44, 14.78], P < 0.00001; NIHSS: MD: -2.94, 95 % CI [-3.50, -2.37], P < 0.00001; SAS: MD: -8.19; 95 % CI: [-9.46, -6.92], P < 0.00001; SDS: MD: -6.46 95 % CI [-7.23, -5.70], P < 0.00001). Subgroup analysis demonstrated that routine nursing, health education, exercise rehabilitation nursing and psychological nursing combined with different community nursing measures were significant in rehabilitation for stroke survivors and there was no heterogeneous in the studies of each subgroup(P > 0.1, I2 < 50 %). CONCLUSION: This meta-analysis demonstrated that community nursing combined with routine nursing might improve activities of daily living, motor function and nerve function, and relieve anxiety and depression in stroke survivors. Overall, community nursing had a significant effect on rehabilitation of stroke survivors. However, this study still has limitations such as the overestimation effects caused by the sample size and the risk of bias caused by interventions. Future research will attempt to overcome these limitations and comprehensively assess the effect of community nursing on the rehabilitation of stroke survivors.

NTRK3 exhibits a pro-oncogenic function in upper tract urothelial carcinomas.

Neurotrophic receptor tyrosine kinase 3 (NTRK3) has pleiotropic functions: it acts not only as an oncogene in breast and gastric cancers but also as a dependence receptor in tumor suppressor genes in colon cancer and neuroblastomas. However, the role of NTRK3 in upper tract urothelial carcinoma (UTUC) is not well documented. This study investigated the association between NTRK3 expression and outcomes in UTUC patients and validated the results in tests on UTUC cell lines. A total of 118 UTUC cancer tissue samples were examined to evaluate the expression of NTRK3. Survival curves were generated using Kaplan-Meier estimates, and Cox regression models were used for investigating survival outcomes. Higher NTRK3 expression was correlated with worse progression-free survival, cancer-specific survival, and overall survival. Moreover, the results of an Ingenuity Pathway Analysis suggested that NTRK3 may interact with the PI3K-AKT-mTOR signaling pathway to promote cancer. NTRK3 downregulation in BFTC909 cells through shRNA reduced cellular migration, invasion, and activity in the AKT-mTOR pathway. Furthermore, the overexpression of NTRK3 in UM-UC-14 cells promoted AKT-mTOR pathway activity, cellular migration, and cell invasion. From these observations, we concluded that NTRK3 may contribute to aggressive behaviors in UTUC by facilitating cell migration and invasion through its interaction with the AKT-mTOR pathway and the expression of NTRK3 is a potential predictor of clinical outcomes in cases of UTUC.

Targeted mitochondrial fluorescence probe with large stokes shift for detecting viscosity changes in vivo and in ferroptosis process.

We created four fluorescent sensors in our work to determine the viscosity of mitochondria. Following screening, the probe Mito-3 was chosen because in contrast to the other three probes, it had a greater fluorescence enhancement, large Stokes shift (113 nm) and had a particular response to viscosity that was unaffected by polarity or biological species. As the viscosity increased from PBS to 90 % glycerol, the fluorescence intensity of probe at 586 nm increased 17-fold. Mito-3 has strong biocompatibility and is able to track changes in cell viscosity in response to nystatin and monensin stimulation. Furthermore, the probe has been successfully applied to detect changes in viscosity caused by nystatin and monensin in zebrafish. Above all, the probe can be applied to the increase in mitochondrial viscosity that accompanies the ferroptosis process. Mito-3 has the potential to help further study the relationship between viscosity and ferroptosis.