Protein kinase FaSnRK2.6 phosphorylates transcription factor FabHLH3 to regulate anthocyanin homeostasis during strawberry fruit ripening.

Strawberry (Fragaria×ananassa) is a model plant for studying non-climacteric fruit ripening regulated by abscisic acid (ABA). However, the signaling of ABA in the regulation of fruit coloration is not fully understood. Here, a transcription factor FabHLH3 key to fruit coloration is identified by yeast two hybrid library screening using FaSnRK2.6 as a bait, an ABA core signaling component negative to ripening. Indeed, this interaction is also confirmed by firefly luciferase complementation assay and pull-down assay. RT-qPCR and Western blotting analysis confirm FabHLH3 is expressed ubiquitously in strawberry and stably during fruit development. Manipulating both FabHLH3 and FaSnRK2.6 expression by overexpression and interference demonstrates that FabHLH3 and FaSnRK2.6 promote and inhibit strawberry fruit coloration, respectively, using the marker gene FaUFGT, key to anthocyanin biosynthesis. FaSnRK2.6 can phosphorylate FabHLH3, which promotes FaUFGT expression by the directly binding to its promoter. The phosphorylation inhibits the binding of FabHLH3 to FaUFGT promoter, consequently suppressing FaUFGT expression. Altogether, FaSnRK2.6, a negative kinase in ripening, interacts with and phosphorylates FabHLH3 to suppress FaUFGT expression. With the increase of ABA content in strawberry fruit ripening, the expression of FaSnRK2.6 decreased, which released FabHLH3 transcription activity and enhanced FaUFGT expression, finally promoting the coloration. Thus, our findings fill a gap how FaSnRK2.6 negatively regulates strawberry fruit coloration and ripening by FabHLH3.

Effects of meaning therapy on spirituality, psychological health, and quality of life in patients with cancer: A systematic review and meta-analysis of randomized controlled trials.

Objective: This study aimed to systematically review studies of meaning therapy on patients with cancer and to evaluate its effectiveness on spiritual outcomes, psychological outcomes, and quality of life (QOL). Methods: A comprehensive literature search were performed in five international databases (PubMed, Embase, Web of Science, The Cochrane Library, and CINAHL) and four Chinese databases (CNKI, Wanfang Data, VIP, and CBM) from the inception to August 2023. The methodological quality of each included studies was evaluated by using the revised Cochrane risk-of-bias tool for randomized trials. The random-effects model or fixed-effects model was utilized for effect size analysis, and the standardized mean difference (SMD) or mean difference (MD) along with its corresponding 95% confidence interval (CI) was computed. Meta-analysis was conducted by using the RevMan software 5.4.1. Results: Eight randomized controlled trials with 1251 participants were included in this review. Meta-analyses revealed that meaning therapy can significantly improve the spiritual outcomes including meaning in life (SMD = -0.48; 95% CI = -0.89 to -0.07; P = 0.02), hopelessness (SMD = -0.30; 95% CI = -0.51 to -0.09; P = 0.005), self-esteem (MD = -2.74; 95% CI = -4.17 to -1.32; P = 0.0002) and spiritual well-being (MD = -3.32; 95% CI = -5.63 to -1.01; P = 0.005), psychological outcomes including anxiety (MD = -0.66; 95% CI = -1.30 to -0.01; P = 0.05), depression (SMD = -0.37; 95% CI = -0.55 to -0.20; P < 0.0001), psychological distress (SMD = -0.35; 95% CI = -0.70 to -0.01; P = 0.04) and desire for hastened death (MD = -0.76; 95% CI = -1.47 to -0.05; P = 0.04), and QOL (SMD = -0.29; 95% CI = -0.50 to -0.09; P = 0.006) in patients with cancer. Conclusions: Meaning therapy has positive effects on improving spirituality, psychological health, and QOL of patients with cancer. More high-quality randomized controlled trials with larger sample sizes are warranted to confirm the results of our review and to clarify the long-term effects of meaning therapy in the future. Systematic review registration: PROSPERO (No. CRD42021278286).

A Fully Integrated Handheld Electrochemical Sensing Platform for Point-of-Care Testing of Escherichia coli O157:H7.

Fully integrated devices that enable full functioning execution without or with minimum external accessories or equipment are deemed to be one of the most desirable and ultimate objectives for modern device design and construction. Escherichia coli O157:H7 (E. coli O157:H7) is often linked to outbreaks caused by contaminated water and food. However, the sensors that are currently used for point-of-care E. coli O157:H7 (E. coli O157:H7) detection are often large and cumbersome. Herein, we demonstrate the first example of a handheld and pump-free fully integrated electrochemical sensing platform with the capability to point-of-care test E. coli O157:H7 in the actual samples of E. coli O157:H7-spiked tap water and E. coli O157:H7-spiked watermelon juice. This platform was made possible by overcoming major engineering challenges in the seamless integration of a microfluidic module for pump-free liquid sample collection and transportation, a sensing module for efficient E. coli O157:H7 testing, and an electronic module for automatically converting and wirelessly transmitting signals into a single and compact electrochemical sensing platform that retains its inimitable stand-alone, handheld, pump-free, and cost-effective feature. Although our primary emphasis in this study is on detecting E. coli O157:H7, this pump-free fully integrated handheld electrochemical sensing platform may also be used to monitor other pathogens in food and water by including specific antipathogen antibodies.

Effect of hypoglycemia on cognitive performance in older patients with diabetes: A meta-analysis.

GOALS: The goal of this study was to use meta-analysis to compile information from various studies to investigate the existence and severity of cognitive impairment in elderly diabetes patients who have hypoglycemic episodes. MATERIALS AND TECHNIQUES: For research studies on the relationship between hypoglycemia and cognitive decline or dementia in persons older than 45 years, we searched the PubMed, EMBASE, Cochrane Library, CNKI, WanFang, CBM and VIP databases for the period 1989 to 2022. We conducted random effects inverse variance on the meta-analysis and used the I2 statistic to assess heterogeneity. RESULT: We selected 44 of the 518 studies we retrieved, 7 being appropriate for meta-analysis. Six thousand and forty-five individuals were involved in total. Both types of older diabetic patients with hypoglycemia performed considerably worse on tests of general intelligence than control participants (standardized mean difference, 0.58; 95% CI, 0.88-0.28). Also, elderly type-2 diabetes patients with hypoglycemic episodes had significantly worse memory performance (standardized mean difference, 0.19; 95% CI, 0.29-0.09). Additionally, we found that older type-2 diabetes patients with hypoglycemia had significantly poorer psychomotor function than those without hypoglycemia (standardized mean difference, 0.51; 95% CI, 0.38-0.63).

Seconds Timescale Synthesis of Highly Stretchable Antibacterial Hydrogel for Skin Wound Closure and Epidermal Strain Sensor.

Effective wound healing is critical for patient care, and the development of novel wound dressing materials that promote healing, prevent infection, and are user-friendly is of great importance, particularly in the context of point-of-care testing (POCT). This study reports the synthesis of a hydrogel material that can be produced in less than 10 s and possesses antibacterial activity against both gram-negative and gram-positive microorganisms, as well as the ability to inhibit the growth of eukaryotic cells, such as yeast. The hydrogel is formed wholly based on covalent-like hydrogen bonding interactions and exhibits excellent mechanical properties, with the ability to stretch up to more than 600% of its initial length. Furthermore, the hydrogel demonstrates ultra-fast self-healing properties, with fractures capable of being repaired within 10 s. This hydrogel can promote skin wound healing, with the added advantage of functioning as a strain sensor that generates an electrical signal in response to physical deformation. The strain sensor composed of a rubber shell realizes fast and responsive strain sensing. The findings suggest that this hydrogel has promising applications in the field of POCT for wound care, providing a new avenue for improved patient outcomes.

Psychometric Properties of the Chinese Version of the Functional Assessment of Chronic Illness Therapy - Palliative Care (FACIT-Pal) in Patients With Advanced Cancer.

CONTEXT: The Functional Assessment of Chronic Illness Therapy-Palliative Care (FACIT-Pal) has been widely used in assessing the quality of life (QOL) of patients with life-limiting illness. However, the Chinese version of the FACIT-Pal has not been psychometrically validated yet. OBJECTIVES: The purpose of this study was to psychometrically validate the FACIT-Pal in Chinese patients with advanced cancer. METHODS: 160 patients with advanced cancer in mainland China participated in this cross-sectional study. The scalability of the instrument was determined by the item-total correlations and the reliability was tested by examining the Cronbach's alpha coefficients. The construct and concurrent validity of the FACIT-Pal were also examined. RESULTS: The item-total correlation coefficients ranged from 0.25 to 0.72 (P < .01). Cronbach's alpha coefficient of the Chinese version of the FACIT-Pal was 0.94, ranging from 0.78 to 0.89 for subscales. Confirmatory factor analysis (CFA) results provided support for the measurement structure of the 26-item Functional Assessment of Cancer Therapy-General (FACT-G). Exploratory factor analysis (EFA) of the 19-item palliative care subscale identified five factors accounting for 62.21% of the total variance. Total/subscale scores of the FACIT-Pal were positively correlated with that of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 Item Scale (FACIT-Sp-12) (r = 0.338-0.811, P < .01), as well as with the Karnofsky Performance Scale (KPS) scores (r = 0.163-0.273, P < .05), except for the correlation between social/family well-being subscale score and KPS score. CONCLUSION: The Chinese version of the FACIT-Pal demonstrates desirable psychometric properties for evaluating QOL in Chinese patients with advanced cancer.

Integrating the multiple functions of CHLH into chloroplast-derived signaling fundamental to plant development and adaptation as well as fruit ripening.

Chlorophyll (Chl)-mediated oxygenic photosynthesis sustains life on Earth. Greening leaves play fundamental roles in plant growth and crop yield, correlating with the idea that more Chls lead to better adaptation. However, they face significant challenges from various unfavorable environments. Chl biosynthesis hinges on the first committed step, which involves inserting Mg2+ into protoporphyrin. This step is facilitated by the H subunit of magnesium chelatase (CHLH) and features a conserved mechanism from cyanobacteria to plants. For better adaptation to fluctuating land environments, especially drought, CHLH evolves multiple biological functions, including Chl biosynthesis, retrograde signaling, and abscisic acid (ABA) responses. Additionally, it integrates into various chloroplast-derived signaling pathways, encompassing both retrograde signaling and hormonal signaling. The former comprises ROS (reactive oxygen species), heme, GUN (genomes uncoupled), MEcPP (methylerythritol cyclodiphosphate), ß-CC (ß-cyclocitral), and PAP (3'-phosphoadenosine-5'-phosphate). The latter involves phytohormones like ABA, ethylene, auxin, cytokinin, gibberellin, strigolactone, brassinolide, salicylic acid, and jasmonic acid. Together, these elements create a coordinated regulatory network tailored to plant development and adaptation. An intriguing example is how drought-mediated improvement of fruit quality provides insights into chloroplast-derived signaling, aiding the shift from vegetative to reproductive growth. In this context, we explore the integration of CHLH's multifaceted roles into chloroplast-derived signaling, which lays the foundation for plant development and adaptation, as well as fruit ripening and quality. In the future, manipulating chloroplast-derived signaling may offer a promising avenue to enhance crop yield and quality through the homeostasis, function, and regulation of Chls.

Artificial enzyme innovations in electrochemical devices: advancing wearable and portable sensing technologies.

With the rapid evolution of sensing technologies, the integration of nanoscale catalysts, particularly those mimicking enzymatic functions, into electrochemical devices has surfaced as a pivotal advancement. These catalysts, dubbed artificial enzymes, embody a blend of heightened sensitivity, selectivity, and durability, laying the groundwork for innovative applications in real-time health monitoring and environmental detection. This minireview penetrates into the fundamental principles of electrochemical sensing, elucidating the unique attributes that establish artificial enzymes as foundational elements in this field. We spotlight a range of innovations where these catalysts have been proficiently incorporated into wearable and portable platforms. Navigating the pathway of amalgamating these nanoscale wonders into consumer-appealing devices presents a multitude of challenges; nevertheless, the progress made thus far signals a promising trajectory. As the intersection of materials science, biochemistry, and electronics progressively intensifies, a flourishing future seems imminent for artificial enzyme-infused electrochemical devices, with the potential to redefine the landscapes of wearable health diagnostics and portable sensing solutions.

Effects of shift work schedules, compensatory sleep, and work-family conflict on fatigue of shift-working nurses in Chinese intensive care units.

BACKGROUND: Shift work is inevitable for nurses in intensive care units. Various studies explored nurses' fatigue in multiple hospital wards. However, few studies focused on fatigue among nurses in intensive care units. AIMS: To determine the association between shift work schedules, compensatory sleep, work-family conflict, and fatigue of shift-working nurses in critical care units. STUDY DESIGN: A descriptive cross-sectional multi-center study was conducted in March 2022 among intensive care nurses from five hospitals. METHODS: Data were collected by online survey, including self-designed demographic questions, the Fatigue Scale-14, the Chinese adult daytime sleepiness scale, and the work-family scale. Pearson correlation was conducted for bivariate analysis. Independent-sample t-test, one-way ANOVA, and multiple linear regression analysis were performed to examine fatigue-related variables. RESULTS: A total of 326 nurses responded to the survey with an effective response rate of 74.9%. The mean scores of physical fatigue and mental fatigue were 6.80 and 3.72, respectively. The bivariate analyses showed that work-family conflict was positively correlated with physical (r = 0.483, p < .001) and mental fatigue (r = 0.406, p < .001). Multiple linear regression results showed that work-family conflict, daytime sleepiness, and shift system were statistically significant factors influencing physical fatigue (F = 41.793, p < .001). Work-family conflict, sleep duration after the night shift, and daytime sleepiness were the main influencing factors of mental fatigue (F = 25.105, p < .001). CONCLUSIONS: Nurses with higher work-family conflict, daytime sleepiness, and working 12-h shifts have higher levels of physical fatigue. Higher work-family conflict, shorter sleep duration after night shifts, and daytime sleepiness are associated with higher mental fatigue among intensive care nurses. RELEVANCE TO CLINICAL PRACTICE: Nursing managers and nurses should consider work-family factors and compensatory sleep in their efforts to reduce fatigue. It is necessary to strengthen work-supporting strategies and compensatory sleep guidance for nurses to promote fatigue recovery.

Universal Fully Integrated Wearable Sensor Arrays for the Multiple Electrolyte and Metabolite Monitoring in Raw Sweat, Saliva, or Urine.

Fully integrated wearable sensors are capable of dynamically, directly, and independently tracking biomarkers in raw noninvasive biofluids without any other equipment or accessories by integrating the unique on-body monitoring feature with the special complete functional implementation attribute. Sweat, saliva, and urine are three important noninvasive biofluids, and changes in their biomarkers hold great potential for revealing physiological conditions. However, it is still a challenge to design single fully integrated wearable sensor arrays (FIWSAs) that are universally able to concurrently measure electrolytes and metabolites in three of the most common noninvasive biofluids including sweat, saliva, and urine. Here, we propose the first single universal FIWSAs for wirelessly, noninvasively, and simultaneously measuring various metabolites (i.e., uric acid) and electrolytes (i.e., Na+ and H+) in raw sweat, saliva, or urine under subjects' exercise by integrating the specifically designed microfluidic, sensing, and electronic modules in a seamless manner. We evaluate its utility for noninvasive gout management in healthy subjects and in gout patients through a purine-rich meal challenge and with a medicine-treatment control, respectively. Noninvasive monitoring of multiple electrolytes and metabolites in a variety of raw noninvasive biofluids via such single universal FIWSAs may enrich the understanding of the biomarkers' levels in the body and would also facilitate self-health management.

Development of an online UPLC-PDA-ESI-Q-TOF-MS-LOX-FLD system for rapid screening of anti-inflammatory compounds in Polygala tenuifolia Willd.

In this study, the first ultra-high performance liquid chromatography-photo-diode array-electrospray ionization-quadrupole-time-of-flight-mass spectrometry-lipoxygenase-fluorescence detector (UPLC-PDA-ESI-Q-TOF-MS-LOX-FLD) online system was developed for the identification and evaluation of anti-inflammatory active ingredients in Polygala tenuifolia Willd. Using this system, the UPLC fingerprints, mass fragments and LOX-binding peak profiles in the samples were rapidly and simultaneously obtained. A total of 101 compounds were isolated and identified and 38 compounds (11 oligosaccharide esters, nine xanthones, 17 saponins, and one glycosyloxyflavone) showed strong LOX-binding activity. Six compounds were selected to study their LOX-binding ability, and the results indicated that the content of the six compounds had a good linear relationship with the LOX-binding ability, and it was found that the substitution position, the type of substituent and the number of glycosyl groups all had a certain influence on the LOX-binding ability of the compounds. The LOX-binding activities of 10 compounds were verified by the surface plasmon resonance (SPR) technique and the activity results were consistent with the online system. After validation, we identified 7 active compounds that combined with LOX to exert anti-inflammatory effects for the first time. All the results fully demonstrate the efficiency, stability and reliability of the online system and this work provides an exemplary and useful method for the rapid screening of potential anti-inflammatory active compounds in P. tenuifolia and other traditional Chinese medicines. At the same time, it provides a new direction for screening small molecule inhibitors of enzymes like LOX.

A Bifunctional Fully Integrated Wearable Tracker for Epidermal Sweat and Wound Exudate Multiple Biomarkers Monitoring.

Fully integrated wearable electronics that combine the extraordinary feature of incessant and on-body operation with the distinctive external equipment-free trait are the ultimate goal of modern wearables. Epidermal sweat and wound exudate, as two noninvasively accessible biofluids on/surrounding the skin, reflect underlying health conditions. However, the design of universal wearable sensors with the bifunctional capability to monitor both epidermal secretions is still a challenge. Here, a single bifunctional fully integrated wearable tracker for wirelessly, simultaneously, and dynamically in situ measuring multiple epidermal sweat or wound exudate biomarkers is propos. Considering the electrolytes (e.g., Na+ , K+ , and H+ ) and metabolites (e.g., uric acid (UA)) levels in sweat or wound exudate may correlate with health or wound conditions, the dynamic and skin-on tracking of the biomarkers of Na+ , K+ , pH, and UA levels in sweat under subjects' exercise and in wound exudate during subjects' wound healing are performed through the seamless integration of microfluidic, sensing, and electronic modules. Its applicability is evaluated for noninvasive hyperuricemia management in hyperuricemia/healthy subjects through a purine-rich intake test and for wound management in subjects' infected wounds through a control medical treatment.

Randomised controlled trial: effect of metformin add-on therapy on functional cure in entecavir-treated patients with chronic hepatitis B.

INTRODUCTION AND OBJECTIVES: Hepatitis B surface antigen (HBsAg) clearance, indicating functional cure or resolved chronic hepatitis B (CHB), remains difficult to achieve via nucleos(t)ide analogue monotherapy. We investigated whether metformin add-on therapy could help achieve this goal in entecavir-treated patients with hepatitis B e antigen (HBeAg)-negative CHB. PATIENTS AND METHODS: Patients with HBeAg-negative CHB who met eligibility criteria (entecavir treatment for > 12 months, HBsAg < 1000 IU/mL) were randomly assigned (1:1) to receive 24 weeks of either metformin (1000 mg, oral, once a day) or placebo (oral, once a day) add-on therapy. The group allocation was blinded for both patients and investigators. Efficacy and safety analyses were based on the intention-to-treat set. The primary outcome, serum HBsAg level (IU/mL) at weeks 24 and 36, was analysed using mixed models. RESULTS: Sixty eligible patients were randomly assigned to the metformin (n = 29) and placebo (n = 31) groups. There was no substantial between-group difference in the HBsAg level at week 24 (adjusted mean difference 0.05, 95% confidence interval -0.04 to 0.13, p = 0.278) or week 36 (0.06, -0.03 to 0.15, p = 0.187), and no significant effect of group-by-time interaction on the HBsAg level throughout the trial (p = 0.814). The occurrence of total adverse events between the two groups was comparable (9 [31.0%] of 29 vs. 5 [16.1%] of 31, p = 0.227) and no patient experienced serious adverse events during the study. CONCLUSION: Although it was safe, metformin add-on therapy did not accelerate HBsAg clearance in entecavir-treated patients with HBeAg-negative CHB.

The Ubiquitin E3 Ligase PRU2 Modulates Phosphate Uptake in Arabidopsis.

Phosphorus is an essential macronutrient for plants. The phosphate (Pi) concentration in soil solutions is typically low, and plants always suffer from low-Pi stress. During Pi starvation, a number of adaptive mechanisms in plants have evolved to increase Pi uptake, whereas the mechanisms are not very clear. Here, we report that an ubiquitin E3 ligase, PRU2, modulates Pi acquisition in Arabidopsis response to the low-Pi stress. The mutant pru2 showed arsenate-resistant phenotypes and reduced Pi content and Pi uptake rate. The complementation with PRU2 restored these to wild-type plants. PRU2 functioned as an ubiquitin E3 ligase, and the protein accumulation of PRU2 was elevated during Pi starvation. PRU2 interacted with a kinase CK2α1 and a ribosomal protein RPL10 and degraded CK2α1 and RPL10 under low-Pi stress. The in vitro phosphorylation assay showed that CK2α1 phosphorylated PHT1;1 at Ser-514, and prior reports demonstrated that the phosphorylation of PHT1;1 Ser-514 resulted in PHT1;1 retention in the endoplasmic reticulum. Then, the degradation of CK2α1 by PRU2 under low-Pi stress facilitated PHT1;1 to move to the plasma membrane to increase Arabidopsis Pi uptake. Taken together, this study demonstrated that the ubiquitin E3 ligase-PRU2-was an important positive regulator in modulating Pi acquisition in Arabidopsis response to low-Pi stress.

A Flexible Microfluidic Chip-Based Universal Fully Integrated Nanoelectronic System with Point-of-Care Raw Sweat, Tears, or Saliva Glucose Monitoring for Potential Noninvasive Glucose Management.

By combining the distinctive noninvasive feature with the peculiar complete functional implementation trait, fully integrated raw noninvasive biofluid glucose biosensors offer active and remote glucose monitoring while posing minimal harm or infection risks compared to the traditional invasive manner. However, each previously reported fully integrated raw noninvasive biofluid glucose biosensor is solely focused on single-type raw noninvasive biofluid analysis. Given the diversity and complexity of subjects' physical conditions, single-type raw noninvasive biofluids are inappropriate to all crowds (e.g., sweat collection/analysis could be inapplicable for dermatopathic subjects). Here, we demonstrate the first example of a universal fully integrated nanoelectronic system with the unique capability to point-of-care and universally monitor diverse raw noninvasive biofluid (i.e., sweat, tears, and saliva) glucose by combining a flexible and disposable microfluidic enzymatic biosensor (named iezSlice) for raw biofluid pump-free sampling and measurement with a customized, handheld, and reusable wireless electronic device (named iezBar) for electrical signal transduction, conditioning, processing, and wireless transmission. We employed the specially designed high-concentration-buffer powder-loaded Kimwipes (HBP-KWs) as the microfluidic channel (microchannel) of iezSlice, guaranteeing a high-accuracy glucose analysis in various raw noninvasive biofluids. We also evaluated the potential utility of the universal fully integrated nanoelectronic system for noninvasive glucose management in healthy and diabetic subjects with the assistance of the proposed volatility-derived blood glucose concentration-free protocol. Although we focus on raw noninvasive biofluid glucose analysis in this work, the universal fully integrated nanoelectronic system may readily realize accurate monitoring of various biomolecules in raw noninvasive biofluids by introducing corresponding bioreceptors.

A prospective evaluation of AI-augmented epidemiology to forecast COVID-19 in the USA and Japan.

The COVID-19 pandemic has highlighted the global need for reliable models of disease spread. We propose an AI-augmented forecast modeling framework that provides daily predictions of the expected number of confirmed COVID-19 deaths, cases, and hospitalizations during the following 4 weeks. We present an international, prospective evaluation of our models' performance across all states and counties in the USA and prefectures in Japan. Nationally, incident mean absolute percentage error (MAPE) for predicting COVID-19 associated deaths during prospective deployment remained consistently <8% (US) and <29% (Japan), while cumulative MAPE remained <2% (US) and <10% (Japan). We show that our models perform well even during periods of considerable change in population behavior, and are robust to demographic differences across different geographic locations. We further demonstrate that our framework provides meaningful explanatory insights with the models accurately adapting to local and national policy interventions. Our framework enables counterfactual simulations, which indicate continuing Non-Pharmaceutical Interventions alongside vaccinations is essential for faster recovery from the pandemic, delaying the application of interventions has a detrimental effect, and allow exploration of the consequences of different vaccination strategies. The COVID-19 pandemic remains a global emergency. In the face of substantial challenges ahead, the approach presented here has the potential to inform critical decisions.

Evaluation of the in situ assay for HBV DNA: An observational real-world study in chronic hepatitis B.

ABSTRACT: The visualization of intrahepatic hepatitis B virus (HBV) DNA by in situ hybridization (ISH) has uncovered some interesting aspects of HBV life cycle at the single-cell level. In the current study, we intend to evaluate the reliability and robustness of this assay in the real-world clinical scenario and its relationship with currently available clinical biomarkers in chronic hepatitis B (CHB) patients.In this cross-sectional study, 94 CHB patients and 10 patients with non-HBV related liver diseases were enrolled. Liver biopsies and routine histopathology analysis were performed. Intrahepatic HBV DNA and viral antigens (HBsAg and HBcAg) were detected by ISH and immunohistochemistry (IHC), respectively. The basic biochemical and virological parameters such as alanine transaminase, serum HBV DNA, and serum HBsAg were measured.The HBV DNA-ISH assay showed 55.8% (53/94 cases) positive rate in CHB patients, no false positive was found in non-HBV related hepatitis. The IHC of HBsAg and HBcAg showed a positive rate of 94.7% (89/94 cases) and 19.5% (17/87 cases), respectively. Quantification of HBV DNA-ISH signal showed a significant correlation with serum HBV DNA (rs = 0.6223, P < .0001). In addition, the staining pattern of HBV DNA in situ in the context of collagen deposition informed the histopathological progression of chronic liver disease.The application of this ISH assay in evaluating intrahepatic viral replication in real-world CHB patients showed favorable performance. It can be a complementation to conventional liver histopathology examination and IHC detection of viral antigens. This methodology provides an intuitive assessment of virological and pathological state of CHB patients, and further supports clinical diagnosis and management.

A Bendable Biofuel Cell-Based Fully Integrated Biomedical Nanodevice for Point-of-Care Diagnosis of Scurvy.

Fully integrated nanodevices that allow the complete functional implementation without an external accessory or equipment are deemed to be one of the most ideal and ultimate goals for modern nanodevice design and construction. In this work, we demonstrate the first example of a bendable biofuel cell (BFC)-based fully integrated biomedical nanodevice with simple, palm-sized, easy-to-carry, pump-free, cost-saving, and easy-to-use features for the point-of-care (POC) diagnosis of scurvy from a single drop of untreated human serum (down to 0.2 µL) by integrating a bendable and disposable vitamin C/air microfluidic BFC (micro-BFC) (named iezCard) for self-powered vitamin C biosensing with a custom mini digital LED voltmeter (named iezBox) for signal processing and transmission, along with a ″built-in″ biocomputing BUFFER gate for intelligent diagnosis. Under the simplicity- and practicability-oriented idea, a cost-effective strategy (e.g., biomass-derived hierarchical micro-mesoporous carbon aerogels, screen-printed technique, a single piece of Kimwipes paper, LED display, and universal components) was implemented for nanodevice design rather than any top-end or pricey method (e.g., photolithography/electron-beam evaporation, peristaltic pump, wireless system, and 3D printing technique), which enormously reduces the cost of feedstock down to ∼USD 2.55 per integrated kit including a disposal iezCard (∼USD 0.08 per test) and a reusable iezBox (∼USD 2.47 for large-scale tests). These distinctive and attractive features allow such a fully integrated biomedical nanodevice to fully satisfy the basic requirements for POC diagnosis of scurvy from a single drop of raw human serum and make it particularly appropriate for resource-poor settings, where there is a lack of medical facilities, funds, and qualified personnel.

The Transcription Factor NIGT1.2 Modulates Both Phosphate Uptake and Nitrate Influx during Phosphate Starvation in Arabidopsis and Maize.

Phosphorus and nitrogen are essential macronutrients for plant growth and crop production. During phosphate (Pi) starvation, plants enhanced Pi but reduced nitrate (NO3 -) uptake capacity, and the mechanism is unclear. Here, we show that a GARP-type transcription factor NITRATE-INDUCIBLE, GARP-TYPE TRANSCRIPTIOANL REPRESSOR1.2 (NIGT1.2) coordinately modulates Pi and NO3 - uptake in response to Pi starvation. Overexpression of NIGT1.2 increased Pi uptake capacity but decreased NO3 - uptake capacity in Arabidopsis (Arabidopsis thaliana). Furthermore, the nigt1.1 nigt1.2 double mutant displayed reduced Pi uptake but enhanced NO3 - uptake under low-Pi stress. During Pi starvation, NIGT1.2 directly up-regulated the transcription of the Pi transporter genes PHOSPHATE TRANSPORTER1;1 (PHT1;1) and PHOSPHATE TRANSPORTER1;4 (PHT1;4) and down-regulated expression of NO3 - transporter gene NITRATE TRANSPORTER1.1 (NRT1.1) by binding to cis-elements in their promoters. Further genetic assays demonstrated that PHT1;1, PHT1;4, and NRT1.1 were genetically epistatic to NIGT1.2 We also identified similar regulatory pathway in maize (Zea mays). These data demonstrate that the transcription factor NIGT1.2 plays a central role in modulating low-Pi-dependent uptake of Pi and NO3 -, tending toward maintenance of the phosphorus to nitrogen balance in plants during Pi starvation.

Thiourea-assistant growth of In2O3 porous pompon assembled from 2D nanosheets for enhanced ethanol sensing performance.

The flower-like porous In2O3 pompon assembled from two-dimensional (2D) nanosheets was synthesized through a simple thiourea-assistant hydrothermal method following the annealed process. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images manifest that the In2O3 pompon possesses a clear porous structure with a nanosheet thickness of about 37.5 nm. Further, we compare the performance of intermediate products (In2S3, In2S3/In2O3) and In2O3 nanostructures as ethanol detection gas sensors. The fabrication of In2O3-based sensors exhibits enhanced ethanol sensing performance than that of In2S3/In2O3-based and In2S3-based sensors, which is mainly attributed to more chemical oxygen and oxygen vacancies on the material surface. The In2O3-based sensors for ethanol detection revealed a wide linear range from 2 ppm to 100 ppm, meanwhile the corresponding detection limits (LOD) as low as ~0.4 ppm at 260 °C. And the In2O3-based sensors also exhibit superior repeatability and reliable selectivity. The simple fabrication strategy of 2D nanosheets-assembled flower-like In2O3 porous pompon may facilitate other ethanol gas sensors production and other 2D metal oxide semiconductor materials-based sensors preparation.