Combined effects of cadmium and simulated acid rain on soil microbial communities in the early cultivation of Populus beijingensis seedlings.

The combined cadmium (Cd) and acid rain pollution poses a significant threat to the global ecological environment. Previous studies on the combined adverse effects have predominantly focused on the aboveground plant physiological responses, with limited reports on the microbial response in the rhizosphere soil. This study employed Populus beijingensis seedlings and potting experiments to simulate the impacts of combined mild acid rain (pH=4.5, MA) or highly strong acid rain (pH=3.0, HA), and soil Cd pollution on the composition and diversity of microbial communities, as well as the physiochemical properties in the rhizosphere soil. The results showed that Cd decreased the content of inorganic nitrogen, resulting in an overall decrease of 49.10 % and 46.67 % in ammonium nitrogen and nitrate nitrogen, respectively. Conversely, acid rain was found to elevate the content of total potassium and soil organic carbon by 4.68 %-6.18 % and 8.64-19.16 %, respectively. Additionally, simulated acid rain was observed to decrease the pH level by 0.29-0.35, while Cd increased the pH level by 0.11. Moreover, Cd alone reduced the rhizosphere bacterial diversity, however, when combined with acid rain, regardless of its intensity, Cd was observed to increase the diversity. Fungal diversity was not influenced by the acid rain, but Cd increased fungal diversity to some extend under HA as observed in bacterial diversity. In addition, composition of the rhizosphere bacterial community was primarily influenced by the inorganic nitrogen components, while the fungal community was driven mainly by soil pH. Furthermore, "Metabolism" was emerged as the most significant bacterial function, which was markedly affected by the combined pollution, while Cd pollution led to a shift from symbiotroph to other trophic types for fungi. These findings suggest that simulated acid rain has a mitigating effect on the diversity of rhizosphere bacteria affected by Cd pollution, and also alters the trophic type of these microorganisms. This can be attributed to the acid rain-induced direct acidic environment, as well as the indirect changes in the availability or sources of carbon, nitrogen, or potassium.

Identification and characterization of a chondroitinase ABC with a novel carbohydrate-binding module.

Chondroitinases play important roles in structural and functional studies of chondroitin sulfates. Carbohydrate-binding module (CBM) is generally considered as an accessory module in carbohydrate-active enzymes, which promotes the association of the appended enzyme with the substrate and potentiates the catalytic activity. However, the role of natural CBM in chondroitinases has not been investigated. Herein, a novel chondroitinase ChABC29So containing an unknown domain with a predicted ß-sandwich fold was discovered from Segatella oris. Recombinant ChABC29So showed enzyme activity towards chondroitin sulfates and hyaluronic acid and acted in a random endo-acting manner. The unknown domain exhibited a chondroitin sulfate-binding capacity and was identified as a CBM. Biochemical characterization of ChABC29So and the CBM-truncated enzyme revealed that the CBM enhances the catalytic activity, thermostability, and disaccharide proportion in the final enzymatic products of ChABC29So. These findings demonstrate the role of the natural CBM in a chondroitinase and will guide future modification of chondroitinases.

ROS-induced oxidative stress is a major contributor to sperm cryoinjury.

STUDY QUESTION: What is the mechanism behind cryoinjury in human sperm, particularly concerning the interplay between reactive oxygen species (ROS) and autophagy, and how does it subsequently affect sperm fate? SUMMARY ANSWER: The freeze-thaw operation induces oxidative stress by generating abundant ROS, which impairs sperm motility and activates autophagy, ultimately guiding the sperm toward programmed cell death such as apoptosis and necrosis, as well as triggering premature capacitation. WHAT IS KNOWN ALREADY: Both ROS-induced oxidative stress and autophagy are thought to exert an influence on the quality of frozen-thawed sperm. STUDY DESIGN, SIZE, DURATION: Overall, 84 semen specimens were collected from young healthy fertile males, with careful quality evaluation. The specimens were split into three groups to investigate the ROS-induced cryoinjury: normal control without any treatment, sperm treated with 0.5 mM hydrogen peroxide (H2O2) for 1 h, and sperm thawed following cryopreservation. Samples from 48 individuals underwent computer-assisted human sperm analysis (CASA) to evaluate sperm quality in response to the treatments. Semen samples from three donors were analyzed for changes in the sperm proteome after H2O2 treatment, and another set of samples from three donors were analyzed for changes following the freeze-thaw process. The other 30 samples were used for fluorescence-staining and western blotting. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sperm motility parameters, including progressive motility (PR %) and total motility (PR + NP %), were evaluated using the CASA system on a minimum of 200 spermatozoa. The proteomic profiles were determined with label-free mass spectrometry (MS/MS) and protein identification was performed via ion search against the NCBI human database. Subsequently, comprehensive bioinformatics was applied to detect significant proteomic changes and functional enrichment. Fluorescence-staining and western blot analyses were also conducted to confirm the proteomic changes on selected key proteins. The ROS level was measured using 2',7'-dichlorodihydrofluorescein diacetate labeling and the abundance of bioactive mitochondria was determined by evaluating the inner mitochondrial membrane potential (MMP) level. Molecular behaviors of sequestosome-1 (p62 or SQSTM1) and microtubule-associated proteins 1A/1B light chain 3 (LC3) were monitored to evaluate the state of apoptosis in human sperm. Fluorescent probes oxazole yellow (YO-PRO-1) and propidium iodide (PI) were utilized to monitor programmed cell death, namely apoptosis and necrosis. Additionally, gradient concentrations of antioxidant coenzyme Q10 (CoQ10) were introduced to suppress ROS impacts on sperm. MAIN RESULTS AND THE ROLE OF CHANCE: The CASA analysis revealed a significant decrease in sperm motility for both the H2O2-treatment and freeze-thaw groups. Fluorescence staining showed that high ROS levels were produced in the treated sperm and the MMPs were largely reduced. The introduction of CoQ10 at concentrations of 20 and 30 µM resulted in a significant rescue of progressive motility (P < 0.05). The result suggested that excessive ROS could be the major cause of sperm motility impairment, likely by damaging mitochondrial energy generation. Autophagy was significantly activated in sperm when they were under oxidative stress, as evidenced by the upregulation of p62 and the increased conversion of LC3 as well as the upregulation of several autophagy-related proteins, such as charged multivesicular body protein 2a, mitochondrial import receptor subunit TOM22 homolog, and WD repeat domain phosphoinositide-interacting protein 2. Additionally, fluorescent staining indicated the occurrence of apoptosis and necrosis in both H2O2-treated sperm and post-thaw sperm. The cell death process can be suppressed when CoQ10 is introduced, which consolidates the view that ROS could be the major contributor to sperm cryoinjury. The freeze-thaw process could also initiate sperm premature capacitation, demonstrated by the prominent increase in tyrosine phosphorylated proteins, verified with anti-phosphotyrosine antibody and immunofluorescence assays. The upregulation of capacitation-related proteins, such as hyaluronidase 3 and Folate receptor alpha, supported this finding. LARGE SCALE DATA: The data underlying this article are available in the article and its online supplementary material. LIMITATIONS, REASONS FOR CAUTION: The semen samples were obtained exclusively from young, healthy, and fertile males with progressive motility exceeding 60%, which might overemphasize the positive effects while possibly neglecting the negative impacts of cryoinjury. Additionally, the H2O2 treatment conditions in this study may not precisely mimic the oxidative stress experienced by sperm after thawing from cryopreservation, potentially resulting in the omission of certain molecular alterations. WIDER IMPLICATIONS OF THE FINDINGS: This study provides substantial proteomic data for a comprehensive and deeper understanding of the impact of cryopreservation on sperm quality. It will facilitate the design of optimal protocols for utilizing cryopreserved sperm to improve applications, such as ART, and help resolve various adverse situations caused by chemotherapy, radiotherapy, and surgery. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the Major Innovation Project of Research Institute of National Health Commission (#2022GJZD01-3) and the National Key R&D Program of China (#2018YFC1003600). All authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Analyzing 20 years of Resting-State fMRI Research: Trends and collaborative networks revealed.

Resting-state functional magnetic resonance imaging (rs-fMRI), initially proposed by Biswal et al. in 1995, has emerged as a pivotal facet of neuroimaging research. Its ability to examine brain activity during the resting state without the need for explicit tasks or stimuli has made it an integral component of brain imaging studies. In recent years, rs-fMRI has witnessed substantial growth and found widespread application in the investigation of functional connectivity within the brain. To delineate the developmental trajectory of rs-fMRI over the past two decades, we conducted a comprehensive analysis using bibliometric tool Citespace. Our analysis encompassed publication trends, authorship networks, institutional affiliations, international collaborations, as well as emergent themes in references and keywords. Our study reveals a remarkable increase in the volume of rs-fMRI publications over the past two decades, underscoring the burgeoning interest and potential within this field. Harvard University stands out as the institution with the highest number of research papers published in the realm of RS-fMRI, while the United States holds the highest overall influence in this domain. The recent emergence of keywords such as "machine learning" and "default mode," coupled with citation surges in reference to rs-fMRI, have paved new avenues for research within this field. Our study underscores the critical importance of integrating machine learning techniques into rs-fMRI investigations, offering valuable insights into brain function and disease diagnosis. These findings hold profound significance for the field of neuroscience and may furnish insights for future research employing rs-fMRI as a diagnostic tool for a wide array of neurological disorders, thus emphasizing its pivotal role and potential as a tool for investigating brain functionality.

The efficacy of schema therapy for personality disorders: a systematic review and meta-analysis.

OBJECTIVE: Personality disorders (PDs) are prevalent and associated with functional impairment and psychological disability. Studies suggest that schema therapy (ST) may be an effective treatment for PDs. This review aimed to evaluate the efficacy of ST in treating PDs. METHOD: We conducted a comprehensive literature search using PubMed, Embase, Web of Science, CENTRAL, PsycInfo, and Ovid Medline. We identified eight randomized controlled trials (587 participants) and seven single-group trials (163 participants). RESULTS: Meta-analyses revealed that ST had a moderate effect size (g = 0.359) compared to control conditions in reducing symptoms of PDs. Subgroup analysis indicated that the effect of ST on different types of PDs varied slightly, and that group ST (g = 0.859) was more effective than individual ST (g = 0.163) in treating PDs. Secondary outcome analysis revealed a moderate effect size (g = 0.256) for ST compared to control conditions in improving quality of life, and ST was found to reduce early maladaptive schema (g = 0.590). Single-group trials analysis showed that ST had a positive effect on PDs (OR = 0.241). CONCLUSION: ST appears to be an effective treatment for PDs, as it reduces symptoms and improves quality of life. This review provides support for the use of ST in the treatment of PDs.

Programmable-Modulated Ultrasonic Transducer Array for Contactless Detection of Viral RNAs.

The current polymerase chain reactions-based nucleic acid tests for large-scale infectious disease diagnosis are always lab-dependent and generate large amounts of highly infectious plastic waste. Direct non-linear acoustic driven of microdroplets provide an ideal platform for contactless spatial and temporal manipulation of liquid samples. Here, a strategy to programmable-manipulate microdroplets using potential pressure well for contactless trace detection is conceptualized and designed. On such contactless modulation platform, up to seventy-two piezoelectric transducers are precisely self-focusing single-axis arranged and controlled, which can generate dynamic pressure nodes for effectively contact-free manipulating microdroplets without vessel contamination. In addition, the patterned microdroplet array can act as contactless microreactor and allow multiple trace samples (1-5 µL) biochemical analysis, and the ultrasonic vortex can also accelerate non-equilibrium chemical reactions such as recombinase polymerase amplification (RPA). The results of fluorescence detection indicated that such programmable modulated microdroplet achieved contactless trace nucleic acid detection with a sensitivity of 0.21 copy µL-1 in only 6-14 min, which is 30.3-43.3% shorter than the conventional RPA approach. Such a programmable containerless microdroplet platform can be used for toxic, hazardous, or infectious samples sensing, opening up new avenues for developing future fully automated detection systems.

Hematopoietic stem cell microtransplantation in patients aged over 70 with acute myeloid leukemia: a multicenter study.

In the era of molecular targeted drugs, elderly patients with acute myeloid leukemia (AML) are still very difficult to treat, especially those older than 70 years. The decline in immune function leads to serious infection and disease recurrence. The microtransplant treatment regimen (MST) chemotherapy combined with allogeneic hematopoietic stem cell infusion is a new cell therapy regimen. The aim of this MST study was to improve the survival of elderly patients by graft versus leukemia action and improving T-cell immune function. From May 2012 to July 2020, one hundred and eleven patients aged 70 to 88 years with de novo AML were analyzed retrospectively. After induction chemotherapy, patients whom complete remission (CR) was achieved were given another 2 cycles of postremission therapy. The MST groups were given allogeneic stem cell infusion after each chemotherapy cycle. CR, leukemia-free survival, and overall survival (OS) were compared between groups. Additionally, the immune function and the T cell receptor (TCR) library of T cells were detected and analyzed. The MST group exhibited an encouragingly high CR rate (63.8%), even in high-risk patients (54%), and this rate was significantly higher than that in the chemotherapy alone group. The 1-year OS of MST patients was 57.7%, and it was 55.9% in the high-risk group. It was only 37.3% in the chemotherapy alone group. Higher numbers of naive T cells were found in the MST population than in the chemotherapy alone group. More updated T-cell clones were observed in MST patients by T-cell receptor repertoire analysis with a next-generation sequencing methodology. These results suggest that MST is a safe and practical regimen conducive to longer-term survival in patients of a highly advanced age with AML. Furthermore, it has broad clinical value in the recovery of immune function in elderly patients.

Smart Janus fabrics for one-way sweat sampling and skin-friendly colorimetric detection.

Functionalized textiles with biofluid management capability have attracted tremendous attention in recent years due to their significant roles in health monitoring and dehydration prevention. Here we propose a one-way colorimetric sweat sampling and sensing system based on a Janus fabric using interfacial modification techniques. The opposite wettability of Janus fabric enables sweat to be quickly moved from the skin surface to the hydrophilic side and colorimetric patches. The unidirectional sweat-wicking performance of Janus fabric not only facilitates adequate sweat sampling but also inhibits the backflow of hydrated colorimetric regent from the assay patch toward the skin, eliminating potential epidermal contaminations. On this basis, visual and portable detection of sweat biomarkers including chloride, pH, and urea is also achieved. The results show that the true concentrations of chloride, pH, and urea in sweat are ∼10 mM, ∼7.2, and ∼10 mM, respectively. The detection limits of chloride and urea are 1.06 mM and 3.05 mM. This work bridges the gap between sweat sampling and a friendly epidermal microenvironment, providing a promising way for multifunctional textiles.

Active Enrichment of Nanoparticles for Ultra-Trace Point-of-Care COVID-19 Detection.

Active enrichment can detect nucleic acid at ultra-low concentrations without relatively time-consuming polymerase chain reaction (PCR), which is an important development direction for future rapid nucleic acid detection. Here, we reported an integrated active enrichment platform for direct hand-held detection of nucleic acid of COVID-19 in nanoliter samples without PCR. The platform consists of a capillary-assisted liquid-carrying system for sampling, integrated circuit system for ultrasound output, and cell-phone-based surface-enhanced Raman scattering (SERS) system. Considering the acoustic responsiveness and SERS-enhanced performance, gold nanorods were selected for biomedical applications. Functionalized gold nanorods can effectively capture and enrich biomarkers under ultrasonic aggregation. Such approaches can actively assemble gold nanorods in 1-2 s and achieved highly sensitive (6.15 × 10-13 M) SERS detection of COVID-19 biomarkers in nanoliter (10-7 L) samples within 5 min. We further demonstrated the high stability, repeatability, and selectivity of the platform, and validated its potential for the detection of throat swab samples. This simple, portable, and ultra-trace integrated active enrichment detection platform is a promising diagnostic tool for the direct and rapid detection of COVID-19.

Distinct brain activity alterations of treatment for bipolar disorders with psychotherapy and drug therapy: activation likelihood estimation meta-analysis.

BACKGROUNDS: Many studies suggest that both psychotherapy and drug therapy are effective in the treatment of bipolar disorders (BDs). However, the pathophysiology of both types of intervention has not been established definitively. METHODS: An activation likelihood estimation meta-analysis was performed to identify the distinct brain activity alterations between psychotherapy and drug therapy for the treatment of BDs. Articles were identified by searching databases including PubMed, Embase, Cochrane Library, and Web of Science databases. Eligible studies on BDs were published up until 10 June 2021. RESULTS: 21 studies were included and we conducted a meta-analysis for different therapies and imaging tasks. After receiving psychotherapy, BD patients showed increased activation in the inferior frontal gyrus (IFG) and superior temporal gyrus. While after taking drug therapy, BD patients displayed increased activation in the anterior cingulate cortex, medial frontal gyrus, IFG, and decreased activation in the posterior cingulate cortex. The regions of brain activity changes caused by psychotherapy were mostly focused on the frontal areas, while drug therapy mainly impacted on the limbic areas. Different type of tasks also affected brain regions which were activated. CONCLUSIONS: Our comprehensive meta-analysis indicates that these two treatments might have effect on BD in their own therapeutic modes. Psychotherapy might have a top-down effect, while drug therapy might have a bottom-up effect. This study may contribute to differential diagnosis of BDs and would be helpful to finding more accurate neuroimaging biomarkers for BD treatment.

[Effects of target tree management of Pinus massoniana plantation on soil nematode community structure at different soil depths]. / ç›®æ ‡æ ‘ç»è¥å¯¹é©¬å°¾æ¾äººå·¥æž—ä¸åŒåœŸå±‚æ·±åº¦åœŸå£¤çº¿è™«ç¾¤è½ç»“æž„çš„å½±å“.

To understand soil nematode community structure at different soil depths and its responses to target tree management, we collected soil samples (0-10, 10-20, and 20-50 cm) and litter samples from the target tree management plots and control plots of Pinus massoniana plantation and analyzed community structure, soil environmental factors, and their relationship. The results showed that target tree management increased the abundance of soil nematodes, with the most significant effect at a depth of 0-10 cm. The highest abundance of herbivores was found in the target tree management treatment, while that of bacterivores was found in the control. Compared with the control, Shannon diversity index, richness index, maturity index of nematodes at 10-20 cm soil layer and Shannon diversity index at 20-50 cm soil layer of target trees were significantly improved. According to the results of Pearson correlation and redundancy analysis, soil pH, total phosphorus, available phosphorus, total potassium, and available potassium were the main environmental factors affecting community structure and composition of soil nematodes. In general, target tree management was conducive to the survival and development of soil nematodes and promoted the sustainable development of P. massoniana plantations.

Internet gaming disorder and tobacco use disorder share neural connectivity patterns between the subcortical and the motor network.

Internet gaming disorder (IGD) and tobacco use disorder (TUD) are globally common, non-substance-related disorders and substance-related disorders worldwide, respectively. Recognizing the commonalities between IGD and TUD will deepen understanding of the underlying mechanisms of addictive behavior and excessive online gaming. Using node strength, 141 resting-state data were collected in this study to compute network homogeneity. The participants included participants with IGD (PIGD: n = 34, male = 29, age: 15-25 years), participants with TUD (PTUD: n = 33, male = 33, age: 19-42 years), and matched healthy controls (control-for-IGD: n = 41, male = 38, age: 17-32 years; control-for-TUD: n = 33, age: 21-27 years). PIGD and PTUD exhibited common enhanced node strength between the subcortical and motor networks. Additionally, a common enhanced resting-state functional connectivity (RSFC) was found between the right thalamus and right postcentral gyrus in PIGD and PTUD. Node strength and RSFC were used to distinguish PIGD and PTUD from their respective healthy controls. Interestingly, models trained on PIGD versus controls could classify PTUD versus controls and vice versa, suggesting that these disorders share common neurological patterns. Enhanced connectivity may indicate a greater association between rewards and behaviors, inducing addiction behaviors without flexible and complex regulation. This study discovered that the connectivity between the subcortical and motor networks is a potential biological target for developing addiction treatment in the future.

Altered white matter functional network in nicotine addiction.

Nicotine addiction is a neuropsychiatric disorder with dysfunction in cortices as well as white matter (WM). The nature of the functional alterations in WM remains unclear. The small-world model can well characterize the structure and function of the human brain. In this study, we utilized the small-world model to compare the WM functional connectivity between 62 nicotine addiction participants (called the discovery sample) and 66 matched healthy controls (called the control sample). We also recruited an independent sample comprising 32 nicotine addicts (called the validation sample) for clinical application. The WM functional network data at the network level showed that the nicotine addiction group revealed decreased small-worldness index (σ) and normalized clustering coefficient (γ) compared with healthy controls. For clinical application, the small-world topology of WM functional connectivity could distinguish nicotine addicts from healthy controls (classification accuracy=0.59323, p = 0.0464). We trained abnormal small-world properties on the discovery sample to identify the severity of nicotine addiction, and the identification was successfully applied to the validation sample (classification accuracy=0.65625, p = 0.0106). Our neuroimaging findings provide direct evidence for WM functional changes in nicotine addiction and suggest that the small-world properties of WM function could be qualified as potential biomarkers in nicotine addiction.

Cognitive behavior therapy for depression in people with epilepsy: A systematic review and meta-analysis.

BACKGROUND: Cognitive behavioral therapy (CBT) is the recommended treatment for depression in patients with epilepsy (PWE). However, there are no studies that calculate the effect size of CBT on depression and quality of life (QoL) in PWE. METHODS: We searched seven electronic databases (PubMed, Web of Science, Embase, Cochrane Library, Clinical Trials, Ovid Medline, and PsycINFO). We included 13 studies examining CBT for depression in PWE and calculated its effect size. RESULTS: A total of 13 studies met the criteria. After treatment, CBT improves depression in PWE (g = 0.36, 95%CI: 0.18 to 0.54, I2 = 50%), and the efficacy maintains during follow-up (g = 0.47, 95%CI: 0.04 to 0.89, I2 = 80%). Subgroup analysis has shown that individual CBT (g = 0.47, 95%CI: 0.20 to 0.73, I2 = 0%) had a greater effect size than group CBT (g = 0.30, 95%CI: 0.07 to 0.53, I2 = 62%) in the treatment of depression. Likewise, CBT has a positive effect on the QoL improvement of PWE (g = 0.34, 95%CI: 0.11 to 0.57, I2 = 64%). In controlling seizures, CBT did not differ from the control group (g = -0.06, 95%CI: -0.32 to 0.19, I2 = 0%). CONCLUSIONS: Cognitive behavioral therapy interventions were effective in improving depression and QoL in PWE, but not effective in controlling seizures. The efficacy of CBT interventions targeting seizure control seems to be uncertain.

Bimetal-organic framework/GOx-based hydrogel dressings with antibacterial and inflammatory modulation for wound healing.

Antibiotic resistance of bacteria and persistent inflammation are critical challenges in treating bacteria infected wounds. Thus, it is urgent to develop versatile wound dressings that possess high-efficiency antibacterial performance and inflammation regulation. Herein, we have successfully constructed a hydrogel wound dressing consisting of the bimetallic metal-organic framework (MOF) loaded with glucose oxidase (GOx), termed as MOF(Fe-Cu)/GOx-polyacrylamide (PAM) gel. Hydrogel dressings can provide an efficient cascade-catalyzed system to accelerate wound healing via synergistic antibacterial and inflammatory modulation. Importantly, the catalytic property of the bimetallic MOF(Fe-Cu) is about five times that of the monometallic MOF(Fe). Based on such a cascade-catalyzed system, the abundant gluconic acid and H2O2 can be continuously produced by decomposing glucose via GOx. Such gluconic acid can notably improve the peroxidase performance of MOF(Fe-Cu), which can further efficiently decompose H2O2 to achieve the antibacterial. Meanwhile, MOF (Fe Cu)/GOx PAM gel can induce macrophages to change into an M2 phenotype, which can accelerate the transformation of the wound microenvironment to a remodeling state and then accelerate angiogenesis and neurogenesis. This work provides multifunctional bioactive materials for accelerating wound healing and will have great potential in clinical applications. STATEMENT OF SIGNIFICANCE: Antibiotic resistance and persistent inflammation are still the critical reasons for the slow healing of bacteria infected wounds. Herein, we prepared a hydrogel wound dressing composed of bimetallic metal organic framework (MOF) loaded with glucose oxidase (GOx). The catalytic activity of the bimetallic MOF(Fe-Cu) is significantly enhanced due to doping of copper, which makes it possess outstanding antibacterial ability based on cascade catalysis. Such dressing can promote the remodeling of inflammatory immunity by regulating macrophage polarization to suppress over-reactive inflammation, further accelerating the healing of bacteria-infected wounds. This study provides an innovative and effective way to accelerate the healing of bacteria infected wound by combining bacteria killing and inflammation modulation.

Integrated microdroplet array platform with temperature controller and micro-stirring for ultra-fast SARS-CoV-2 detection.

The outbreak of COVID-19 has created a huge challenge to global health systems. Experience in fighting the epidemic shows that the development of a rapid and sensitive POCT diagnostic platform for SARS-CoV-2 that can be deployed in situ is crucial to contain the outbreak. Here, we have developed a portable microdroplet detection platform that integrated temperature controller and micro-stirring for high-throughput and ultrafast COVID-19 diagnosis. Such a device uses a p-n junction (PN junction) as the temperature controller to adjust the temperature in a single microdroplet independently and precisely, ensuring the amplification of reverse transcription loop-mediated isothermal amplification (RT-LAMP). Meanwhile, the platform incorporates an ultrasonic micro-stirring unit, greatly increasing the interaction between RT-LAMP molecules and accelerating the amplification. The results show good linearity over a wide linear range (1 to 105 copies/µL) and low LOD (0.48 copy/µL). Our method reports in only 6.1 min for high-viral load samples, and combines with sample preparation, the total detection process could be done within 30 min. Such a portable and fully integrated microdroplet molecular diagnostic platform is a promising tool for point-of-care diagnosis of COVID-19 and other infectious diseases in resource-limited settings.

Cyclosporin A Inhibits the Activation of Membrane-Bound Guanylate Cyclase GC-A of Atrial Natriuretic Factor via NAD(P)H Oxidase.

Cyclosporin A (CsA) is a common immunosuppressant wildly used in patients with organ transplant and autoimmune diseases; however, it can cause several adverse effects, such as nephrotoxicity and hypertension. The detailed mechanisms have not been completely understood. Atrial natriuretic factor (ANF) and its receptor (mGC-A) have been shown to play a crucial role in the regulation of blood pressure. Here, we investigated the effects of CsA on the activation of mGC-A in ANF-treated LLC-PK1 cells. In our study, ANF-induced mGC-A activities and superoxide generation in LLC-PK1 cells were measured by guanosine 3',5'-cyclic monophosphate (cGMP) radioimmunoassay and lucigenin-dependent chemiluminescence, respectively. We found that CsA can reduce about 60% of mGC-A activities in ANF-treated LLC-PK1 cells. CsA is known to induce superoxide. Addition of superoxide generators menadione and diamide mimicked the effects of CsA, whereas DPI (a reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase inhibitor) and Tiron (a superoxide quencher) blocked the suppressive effects of CsA on ANF-induced mGC-A activities. We previously showed that the catalytic domain of GC-A (GC-c) expresses guanylate cyclase activities. Addition of menadione, diamide, or peroxynitrite or transfection of Nox-4 NAD(P)H oxidase abolished GC-c activities. In conclusion, CsA inhibits ANF-stimulated mGC-A activities through superoxide and/or peroxynitrite generated by an NAD(P)H oxidase by interacting with the catalytic domain of mGC-A.

Stand structure adjustment influences the biomass allocation in naturally generated Pinus massoniana seedlings through environmental factors.

The natural regeneration of seedlings is a key factor for forest succession. Nevertheless, studies explaining the mechanism of growth and biomass allocation in regenerated seedlings after disturbance are lacking. Therefore, we measured the growth, biomass accumulation, and biomass allocation in current-age seedlings of Pinus massoniana after selective logging (logging of competitive trees, LCT; logging of inferior trees, LIT; and unlogged control, CK), and established structural equation models (SEMs) among the spatial structure characteristic indexes of the stand, environmental factors, and biomass allocation in different organs. As compared to the CK, the mingling index (M), uniform angle index (W), opening degree (O), soil organic carbon (SOC), available nitrogen (SAN), available phosphorus (SAP), available potassium (SAK), and bulk density (SBD) significantly increased (p < 0.05), while the competition index (CI) and neighborhood comparison (U) significantly decreased after logging (p < 0.05). After the LCT, seedling branch biomass improved, with an increase in the ground-diameter, crown-root ratio, and seedling quality index. More biomass was allocated to foliage and roots by an increase in the height and height-diameter ratio under the LIT. In the CK, increasing stem biomass helped the seedlings absorb and utilize more light. The Pearson correlation coefficient showed that biomass allocation to organs was independent, and seedlings adopted the strategies of heterogeneous adaptation and growth, thereby resulting in the separation of the allocation patterns among the organs. As per the redundancy analysis (RDA), CI was the main factor in biomass allocation. Environmental factors had direct effects on biomass allocation to organs, while the stand spatial structure characteristic indexes had indirect effects on biomass allocation based on SEMs. In summary, the LCT had significant, albeit indirect, effects on SOC, SAN, and SBD by reducing the CI for the regeneration and growth of seedlings in the stand, which was of great significance to the sustainable development of the forest stand of P. massoniana.

A retrospective study of prevalence and pattern of international consensus on ANA patterns among patients with hepatitis C virus infection.

Background: A previous study reported a 30% prevalence of various autoantibodies among patients with hepatitis C virus (HCV) infection. The International Consensus on Anti-Nuclear Antibody (ANA) Patterns was recently introduced to classify ANA patterns based on immunoassay on HEp-2 cells. There is no previous report with this newly developed classification to evaluate patients with HCV infection. The study aims to study the prevalence and pattern of ANA patterns among HCV-infected patients. Methods: We retrospectively analyzed the medical records of patients with HCV infection from September 2020 to June 2021 at our institution. A positive ANA is defined as a titer of more than 1:320. We compared patient features among the positive and negative groups. Results: Overall, 258 patients were enrolled-184 patients with negative ANA and 74 patients (28.7%) with positive ANA. The mean age was 67.3 in ANA positive group and 61.2 ANA negative group. Female was prominent with ANA positive and accounted for 63.5%. The most detected ANA pattern was AC-1(homogeneous) (25.9%), followed by AC-4(fine speckled) (25.2%) and AC-21(anti-mitochondrial antibody) (9.6%). In ANA positive group, we found a trend of lower HCV viral load (5.72 log10 IU/ML vs. 6.02 log10 IU/ML), lower alanine aminotransferase level (39.5 U/L vs. 44 U/L), and higher advanced fibrosis (F3 and F4) (38.5% vs. 26.1%). In addition, higher positive ANA (more than 1:640) is significantly associated with lower estimated glomerular filtration rate (eGFR) (77.76 vs. 87.94 mL/min/1.73 m2, P = 0.044). Conclusions: A high prevalence (28.7%) of ANA was found in patients with chronic hepatitis C. The presence of positive ANA is not related to the severity of their hepatic manifestation. However, higher positive ANA was significantly associated with lower eGFR.