Universal digital high-resolution melting for the detection of pulmonary mold infections.

Invasive mold infections (IMIs) are associated with high morbidity, particularly in immunocompromised patients, with mortality rates between 40% and 80%. Early initiation of appropriate antifungal therapy can substantially improve outcomes, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive mycological findings. Universal digital high-resolution melting (U-dHRM) analysis may enable rapid and robust diagnoses of IMI. A universal fungal assay was developed for U-dHRM and used to generate a database of melt curve signatures for 19 clinically relevant fungal pathogens. A machine learning algorithm (ML) was trained to automatically classify these pathogen curves and detect novel melt curves. Performance was assessed on 73 clinical bronchoalveolar lavage samples from patients suspected of IMI. Novel curves were identified by micropipetting U-dHRM reactions and Sanger sequencing amplicons. U-dHRM achieved 97% overall fungal organism identification accuracy and a turnaround time of ~4 hrs. U-dHRM detected pathogenic molds (Aspergillus, Mucorales, Lomentospora, and Fusarium) in 73% of 30 samples classified as IMI, including mixed infections. Specificity was optimized by requiring the number of pathogenic mold curves detected in a sample to be >8 and a sample volume to be 1 mL, which resulted in 100% specificity in 21 at-risk patients without IMI. U-dHRM showed promise as a separate or combination diagnostic approach to standard mycological tests. U-dHRM's speed, ability to simultaneously identify and quantify clinically relevant mold pathogens in polymicrobial samples, and detect emerging opportunistic pathogens may aid treatment decisions, improving patient outcomes. IMPORTANCE: Improvements in diagnostics for invasive mold infections are urgently needed. This work presents a new molecular detection approach that addresses technical and workflow challenges to provide fast pathogen detection, identification, and quantification that could inform treatment to improve patient outcomes.

Hydroamination of Unactivated Alkenes with Aliphatic Azides.

We report here an efficient and highly diastereoselective intermolecular anti-Markovnikov hydroamination of unactivated alkenes with aliphatic azides in the presence of silane. The system tolerates a wide range of azides and alkenes and operates with alkene as limiting reagent. Mechanistic studies suggest a radical chain pathway that involves aminium radical formation, radical addition to alkenes and HAT from silane to ß-aminium alkyl radical. The use of sterically bulky silane is proposed to contribute to the excellent diastereoselectivity for HAT. Computational analysis uncovers the reaction pathway of aliphatic azide activation with silyl radical for aminyl radical formation.

High removal efficiency of antibiotic resistance genes in swine wastewater via nanofiltration and reverse osmosis processes.

Swine wastewater treatment plant has become one of the main sources of antibiotic resistance genes (ARGs). Membrane treatment processes are promising solutions for removal of the emerging contaminants. However, limited studies have investigated the effects of nanofiltration and reverse osmosis treatment in removing ARGs in swine wastewater. In this study, the presence and the fate of common ARGs including sul1, sul2, tetA, tetM and tetW, as well as intI1 and 16S rRNA gene, were investigated in a medium-sized (6500) pig farm wastewater treatment plant (WWTP) equipped with conventional biological treatment and advanced membrane processing system. All of the genes were detected with highly abundance in the raw sewage. The biological treatments of the swine wastewater treatment plant did not reduce the quantity of the ARGs. As expected, nanofiltration and reverse osmosis treatment reduced the absolute gene copy number of ARGs efficiently (4.98-9.52 logs removal compared to raw sewage). Compared to the reverse osmosis effluent, however, the absolute abundance of ARGs in the artificial wetland increased by 1.00-2.06 logs. Meanwhile, the relative abundance of sulfonamide resistant genes were basically unchanged, while tetracycline resistance genes (tetA, tetM and tetW) decreased by 0.88, 3.47, 2.51 log, respectively. The results demonstrated that advanced membrane treatments are capable of removing various kinds of ARGs efficiently, as well as some common nitrogen and phosphorus contaminants. This study suggested a mature alternative method for the removal of ARGs from livestock wastewater.

Siderite's green revolution: From tailings to an eco-friendly material for the green economy.

Siderite, extensively mined as a natural iron mineral, is often discarded as tailings due to the low grade of the ore and due to the high cost of current sorting technologies. Yet, this mineral has demonstrated significant potential in several pivotal areas of the environmental remediation. Siderite not only possesses exceptional adsorption, catalytic, and microbial carrier capabilities but also offers an eco-friendly and cost-effective solution for the environmental pollution management. This article consolidates research advancements and achievements over the past few decades concerning siderite's role in pollution control, delving deeply into its various remediation pathways. Initially, the paper contrasts the performance differences between natural and synthetic siderite, followed by a comprehensive overview of siderite's adsorption mechanisms for various inorganic pollutants. Furthermore, this paper analyzes the unique physicochemical attributes of siderite as both, a reductant and the catalyst, with a special emphasis on its use in the preparation of SCR catalysts and in the catalytic advanced oxidation processes for organic pollutants' degradation. This paper also enumerates and discusses the myriad advantages of siderite as a microbial carrier, thereby enhancing our understanding of biogeochemical cycles and pollutant transformations. In essence, this review systematically elucidates the mechanisms and intrinsic physicochemical properties of siderite in pollution control, paving the way for novel strategies to augment siderite's environmental remediation performance.

Exploring the Underlying Mechanisms of Qingxing Granules Treating H1N1 Influenza Based on Network Pharmacology and Experimental Validation.

BACKGROUND: H1N1 is one of the major subtypes of influenza A virus (IAV) that causes seasonal influenza, posing a serious threat to human health. A traditional Chinese medicine combination called Qingxing granules (QX) is utilized clinically to treat epidemic influenza. However, its chemical components are complex, and the potential pharmacological mechanisms are still unknown. METHODS: QX's effective components were gathered from the TCMSP database based on two criteria: drug-likeness (DL ≥ 0.18) and oral bioavailability (OB ≥ 30%). SwissADME was used to predict potential targets of effective components, and Cytoscape was used to create a "Herb-Component-Target" network for QX. In addition, targets associated with H1N1 were gathered from the databases GeneCards, OMIM, and GEO. Targets associated with autophagy were retrieved from the KEGG, HAMdb, and HADb databases. Intersection targets for QX, H1N1 influenza, and autophagy were identified using Venn diagrams. Afterward, key targets were screened using Cytoscape's protein-protein interaction networks built using the database STRING. Biological functions and signaling pathways of overlapping targets were observed through GO analysis and KEGG enrichment analysis. The main chemical components of QX were determined by high-performance liquid chromatography (HPLC), followed by molecular docking. Finally, the mechanism of QX in treating H1N1 was validated through animal experiments. RESULTS: A total of 786 potential targets and 91 effective components of QX were identified. There were 5420 targets related to H1N1 and 821 autophagy-related targets. The intersection of all targets of QX, H1N1, and autophagy yielded 75 intersecting targets. Ultimately, 10 core targets were selected: BCL2, CASP3, NFKB1, MTOR, JUN, TNF, HSP90AA1, EGFR, HIF1A, and MAPK3. Identification of the main chemical components of QX by HPLC resulted in the separation of seven marker ingredients within 195 min, which are amygdalin, puerarin, baicalin, phillyrin, wogonoside, baicalein, and wogonin. Molecular docking results showed that BCL2, CASP3, NFKB1, and MTOR could bind well with the compounds. In animal studies, QX reduced the degenerative alterations in the lung tissue of H1N1-infected mice by upregulating the expression of p-mTOR/mTOR and p62 and downregulating the expression of LC3, which inhibited autophagy. CONCLUSIONS: According to this study's network pharmacology analysis and experimental confirmation, QX may be able to treat H1N1 infection by regulating autophagy, lowering the expression of LC3, and increasing the expression of p62 and p-mTOR/mTOR.

Iron-Catalyzed Photoredox Alcohol α-C-H Alkylation and Tandem Intramolecular Cyclization: Facile Access to Multisubstituted 2,3-Dihydrofurans and γ-Butyrolactones.

Multisubstituted furans occupy a pivotal position within the realms of synthetic chemistry and pharmacological science due to their distinctive chemical configurations and inherent properties. We herein introduce a tandem difunctionalization protocol of alcohols for the efficient synthesis of multisubstituted 2,3-dihydrofurans and γ-butyrolactones through the combination of photocatalysis and iron catalysis under mild conditions. Photoredox alcohol α-C(sp3)-H activation and Pinner-type intramolecular cyclization are two key processes. This method features significant convenience, economic benefits, and environmental friendliness.

Suppressing Bulk Strain and Surface O2 Release in Li-Rich Cathodes by Just Tuning the Li Content.

Layered oxides represent a prominent class of cathodes employed in lithium-ion batteries. The structural degradation of layered cathodes causes capacity decay during cycling, which is generally induced by anisotropic lattice strain in the bulk of cathode particle and oxygen release at the surface. However, particularly in lithium-rich layered oxides (LLOs) that undergo intense oxygen redox reactions, the challenge of simultaneously addressing bulk and surface issues through a singular modification technique remains arduous. Here a thin (1-nm) and coherent spinel-like phase is constructed on the surface of LLOs particle to suppress bulk strain and surface O2 release by just adjusting the amount of lithium source during synthesis. The spinel-like phase hinders the surface O2 release by accommodating O2 inside the surface layer, while the trapped O2 in the bulk impedes strain evolution by ≈70% at high voltages compared with unmodified LLOs. Consequently, the enhanced structural stability leads to an improved capacity retention of 97.6% and a high Coulombic efficiency of ≈99.5% after 100 cycles at 0.1°C. These findings provide profound mechanistic insights into the functioning of surface structure and offer guidance for synthesizing high-capacity cathodes with superior cyclability.

Healable Ionic Conductors with Extremely Low-Hysteresis and High Mechanical Strength Enabled by Hydrophobic Domain-Locked Reversible Interactions.

Extremely low hysteresis, high mechanical strength, superior toughness, and excellent healability are essential for stretchable ionic conductors to enhance their reliability and meet for cutting-edge applications. However, the fabrication of stretchable ionic conductors with such mutually exclusive properties remains challenging. Herein, extremely low-hysteresis and healable ionic conductors with a tensile strength of ≈8.9 MPa and toughness of ≈23.2 MJ m-3 are fabricated through the complexation of 4-carboxybenzaldehyde (CBA) grafted poly(vinyl alcohol) (PVA) (denoted as PVA-CBA) and poly (allylamine hydrochloride) (PAH) followed by acidification and ion-loading steps. The acidification step generates the PVA-CBA/PAH ionic conductors with in situ formed dynamic hydrophobic domains that lock and stabilize noncovalent interactions. This significantly minimizes the energy dissipation of the ionic conductors during cyclic mechanical loading (≤200% strain), resulting in ionic conductors with extremely low hysteresis (≈5%). The fractured ionic conductors can be healed at 60 °C to restore their original properties. Because of the extremely low hysteresis, the PVA-CBA/PAH ionic conductors show a highly stable and reproducible electrical response over 5000 uninterrupted loading-unloading cycles at a strain of 200%. The ionic conductor based sensors exhibit a high sensitivity to a wide range of strains (1-500%).

High ambient temperature increases the number of emergency visits for upper urolithiasis in Hefei City, China.

Background: Few studies have examined the effect of ambient temperature on upper urolithiasis in developing countries, with even fewer considering individual factors. Methods: The present study analyzed data on emergency department visits for upper urolithiasis from three hospital sites of a large hospital in Hefei, China, during 2016-2020. Data on environmental factors during the same period were also analyzed. A time series analysis employing a generalized Poisson regression model (GPRM) combined with a distributed lag non-linear model (DLNM) was conducted to evaluate the effect of ambient temperature on the number of emergency department visits for upper urolithiasis. Results: We found that ambient temperatures above 9 °C were positively associated with the frequency of upper urolithiasis visits, with the relationship being most significant on the current day and with a one-day lag. In the single-day lag effect, the most significant relative risk (RR) for mild heat (75th percentile) and high heat (95th percentile) was 1.229 (95% CI: 1.100-1.373) and 1.337 (95% CI: 1.134-1.577), respectively. The cumulative lag effect was significantly higher than the single-day lag effect, with maximum relative risks (RRs) of 1.779 (95% CI: 1.356-2.335) and 2.498 (95% CI: 1.688-3.697), respectively. The maximum lag time was 7 days. RRs were also higher among women and individuals aged 30-44 years. Conclusions: Increased ambient temperature is a risk factor for upper urolithiasis, and there is a hysteresis effect. Women and individuals aged 30-44 years are the most susceptible.

Universal Digital High Resolution Melt for the detection of pulmonary mold infections.

Background: Invasive mold infections (IMIs) such as aspergillosis, mucormycosis, fusariosis, and lomentosporiosis are associated with high morbidity and mortality, particularly in immunocompromised patients, with mortality rates as high as 40% to 80%. Outcomes could be substantially improved with early initiation of appropriate antifungal therapy, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive mycological findings. Universal digital high resolution melting analysis (U-dHRM) may enable rapid and robust diagnosis of IMI. This technology aims to accomplish timely pathogen detection at the single genome level by conducting broad-based amplification of microbial barcoding genes in a digital polymerase chain reaction (dPCR) format, followed by high-resolution melting of the DNA amplicons in each digital reaction to generate organism-specific melt curve signatures that are identified by machine learning. Methods: A universal fungal assay was developed for U-dHRM and used to generate a database of melt curve signatures for 19 clinically relevant fungal pathogens. A machine learning algorithm (ML) was trained to automatically classify these 19 fungal melt curves and detect novel melt curves. Performance was assessed on 73 clinical bronchoalveolar lavage (BAL) samples from patients suspected of IMI. Novel curves were identified by micropipetting U-dHRM reactions and Sanger sequencing amplicons. Results: U-dHRM achieved an average of 97% fungal organism identification accuracy and a turn-around-time of 4hrs. Pathogenic molds (Aspergillus, Mucorales, Lomentospora and Fusarium) were detected by U-dHRM in 73% of BALF samples suspected of IMI. Mixtures of pathogenic molds were detected in 19%. U-dHRM demonstrated good sensitivity for IMI, as defined by current diagnostic criteria, when clinical findings were also considered. Conclusions: U-dHRM showed promising performance as a separate or combination diagnostic approach to standard mycological tests. The speed of U-dHRM and its ability to simultaneously identify and quantify clinically relevant mold pathogens in polymicrobial samples as well as detect emerging opportunistic pathogens may provide information that could aid in treatment decisions and improve patient outcomes.

Porridge for influenza: Protocol for a systematic review and meta-analysis.

BACKGROUND: Influenza is a common disease. If it is not treated in time, it may induce related chronic respiratory diseases and seriously endanger people's health. Porridge, as a food of the East, has been recorded by doctors of all ages to treat influenza with porridge. However, due to insufficient research, there is a certain controversy about porridge in the treatment of influenza. We therefore plan to conduct a systematic review and meta-analysis to collect data from all published studies on this issue in order to obtain reliable evidence. METHOD AND ANALYSIS: We will search for relevant trials in various databases published by December 2022. To study the efficacy and safety of a RCT of porridge in the treatment of influenza. Standardized data tables will be used to complete data search and extraction in duplicate. All differences will be resolved by consensus. The main result was to observe the symptom score of influenza patients, and the secondary results included body temperature, nasal secretions, nasal resistance and viral culture titers in the nasal secretions. Data synthesis and statistical analysis will be performed for each outcome with Stata V.14.0. RESULTS: Our study will be a systematic review and meta-analysis to evaluate the efficacy and safety of porridge in the treatment of influenza. CONCLUSION: The conclusion of this study has a certain reference value for the clinical use of porridge in the treatment of influenza.

Meditation programs for adults with type 2 diabetes mellitus: A protocol for a systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes mellitus is intimately linked to chronic stress. Meditation programs belong to mind-body therapies, which could benefit patients' disease management. Though some clinical trials have proved that meditation programs have the ability to improve level of blood glucose quality of life, body mass index and blood indexes related to metabolism in individuals with type 2 diabetes mellitus, the efficacy of meditation programs needs further confirmation. Thus we will conduct this systematic evaluation and meta-analysis to summarize and analyze all the results included to obtain reliable evidence. METHODS: We will search several English and Chinese databases for relevant clinical trials published up to July 2021, and randomized controlled trials or controlled trials among adults with type 2 diabetes mellitus are included. Two reviewers will extract data and assess the quality of included studies independently. The main outcomes of this research are glycosylated hemoglobin level and fasting blood glucose level. The secondary outcomes are high-density lipoprotein, low-density lipoprotein, body mass index, remission of depression and anxiety, and quality of life. Stata v.14.0 and Review Manager V5.3 will be used to synthesize and analyze all data included. RESULTS: Grading of Recommendations Assessment, Development, and Evaluation will be used to evaluate the quality of the assessments. Our study will be disseminated through publications in peer-reviewed journals. CONCLUSION: This systematic review is the first to analyze the efficacy of different types of meditation for type 2 diabetes mellitus, which could provide evidence for the use of mediation programs as non-drug approaches. TRIAL REGISTRATION NUMBER: PROSPERO CRD42021274508.

An MXene-Based Metal Anode with Stepped Sodiophilic Gradient Structure Enables a Large Current Density for Rechargeable Na-O2 Batteries.

The metal anode is the pivotal component for advanced sodium-metal batteries such as Na-O2 batteries. Designing a 3D confinement scaffold is a promising strategy for constructing dendrite-free sodium-metal anodes; however, cycling stability at a large current density (>10 mA cm-2 ) is still difficult to realize. Herein, the design of new lightweight and fibrous hydroxylated Ti3 C2 (h-Ti3 C2 ) MXene based scaffolds with stepped sodiophilic gradient structure (h-M-SSG) is reported, and its thickness can be controlled (80-250 µm). The sodiophilic gradient structure (adjusted by h-Ti3 C2 ) can effectively induce sodium ions to preferentially deposit at the bottom of the scaffold, thus inhibiting dendrite growth. h-M-SSG/Na-based symmetrical batteries exhibit a low polarization voltage and long cycling life at a high current density (40 mA cm-2 ) and a high cut-off capacity (40 mAh cm-2 ). Moreover, a Na-O2 battery with an h-M-SSG/Na anode exhibits a low potential gap of 0.137 V after 45 cycles at 1000 mA g-1 and 1000 mAh g-1 . This deposition-regulation strategy would inspire the design of 3D scaffolds for high-performance sodium-metal-anode-based batteries.

Vanillic acid attenuates H2O2-induced injury in H9c2 cells by regulating mitophagy via the PINK1/Parkin/Mfn2 signaling pathway.

Vanillic acid, a phenolic compound mainly obtained from the foot of Picrorhiza scrophulariiflora Pennell, has been demonstrated to possess a cardiovascular-protective effect in previous studies. However, there is lack of research on vanillic acid protecting cardiomyocytes from oxidative stress injury by mediating mitophagy. In the present study, oxidative stress injury in the H9c2 cell line was induced by H2O2. Our results confirmed that vanillic acid mitigated apoptosis and injury triggered by oxidative stress, evidenced by the decline in production of reactive oxygen species and malondialdehyde and level of lactate dehydrogenase and the increase of superoxide dismutase and glutathione. The use of vanillic acid could also improve the polarization of mitochondrial membrane potential and decrease the cellular calcium level. After treatment by vanillic acid, impaired autophagy flux and mitophagy were improved, and the length of mitochondria was restored. Vanillic acid increased the expression of PINK1, Parkin, Mfn2, and the ratio of LC3-II/LC3-I and decreased the expression of p62. But, under the intervention of mitophagy inhibitor 3-MA, vanillic acid could not change the expression of PINK1/Parkin/Mfn2 and downstream genes to affect cell autophagy, mitophagy, and mitochondrial function. Our findings suggested that vanillic acid activated mitophagy to improve mitochondrial function, in which the PINK1/Parkin/Mfn2 pathway could be the potential regulatory mechanism.

Prevalence and genetic-phenotypic characteristics of patients with USH2A mutations in a large cohort of Chinese patients with inherited retinal disease.

AIMS: To investigate the frequency of USH2A mutation and the clinical and genetic differences between Usher syndrome type II (USH2) and retinitis pigmentosa (RP) in a large cohort of Chinese patients. METHODS: A total of 1381 patients with inherited retinal disease (IRD) were recruited. The phenotypic and genotypic information of patients with USH2A mutations was evaluated. RESULTS: The prevalence of patients with USH2A mutations was 15.75%, which was the most frequently detected gene in this cohort of patients. Hotspot of USH2A mutations was c.8559-2A >G and c.2802T >G. Patients with USH2 had an earlier and more serious decline of visual function and damage to retina structure than did patients with RP in the first 10 years (p<0.05), but there was no difference in the visual prognosis between the two groups when the course of disease exceeded 10 years (p>0.05). Missense variants had less severe consequences and were found more commonly in RP, whereas more deleterious genotypes were associated with an earlier onset of disease and were found more commonly in USH2. CONCLUSIONS: This study provides detailed clinical-genetic assessment of patients with USH2A mutations of Chinese origin, enabling precise genetic diagnoses, better management of these patients and putative therapeutic approaches.

Clinical and Genetic Characteristics of Chinese Patients with Occult Macular Dystrophy.

Purpose: To investigate the clinical and genetic characteristics of occult macular dystrophy (OMD) based on a Chinese patient cohort. Methods: Fifteen Chinese OMD patients from nine unrelated families underwent genetic testing, and all of them harbored a pathogenic RP1L1 variant. Comprehensive ophthalmic examinations were performed in nine probands, including spectral-domain optical coherence tomography (SD-OCT), near-infrared reflectance (NIR), fundus autofluorescence (AF), and multifocal electroretinography. Results: The RP1L1 variants p.R45W and p.S1199C were identified in 13 patients and two patients, respectively, and one was a de novo mutation. Among the nine probands, the median ages at onset and examination were 25.0 years (range, 6-51 years) and 27.0 years (range, 14-55 years), respectively. The median decimal visual acuity was 0.20 (range, 0.04-0.5). Foveal photoreceptor thickness and visual acuity showed a significant correlation (r = 0.591; P = 0.01). All eyes presented with an absent interdigitation zone and blurred ellipsoid zone of photoreceptors when examined by SD-OCT. In addition, central round lesions with low NIR reflectance were observed in 66.7% (12/18) of eyes by NIR reflectance imaging, corresponding to the regions with abnormal photoreceptor microstructures observed by SD-OCT. Of the 18 eyes, only four eyes showed ring-like faint hyperfluorescence around the macula by AF. Conclusions: To the best of our knowledge, this is the largest study in a cohort of Chinese OMD patients with RP1L1 mutations. Our findings revealed that the two recurrent RP1L1 variants are related to OMD in the Chinese population. Furthermore, multimodal imaging combined with genetic testing is valuable for diagnosing and monitoring OMD progression.

Nitrogen-Coordinated Boroxines Enable the Fabrication of Mechanically Robust Supramolecular Thermosets Capable of Healing and Recycling under Mild Conditions.

The fabrication of mechanically robust polymeric materials capable of self-healing and recycling remains challenging because the mobility of polymer chains in such polymers is very limited. In this work, mechanically robust supramolecular thermosets capable of healing physical damages and recycling under mild conditions are fabricated by trimerization of bi-( ortho-aminomethyl-phenylboronic acid)- and tri-( ortho-aminomethyl-phenylboronic acid)-terminated poly(propylene glycol) oligomers (denoted as Bi-PBA-PPG and Tri-PBA-PPG, respectively). The resultant supramolecular thermosets are cross-linked by dynamic covalent bonds of nitrogen-coordinated boroxines. The mechanical properties of the supramolecular thermosets can be systematically tailored by varying the ratios between Tri-PBA-PPG and Bi-PBA-PPG, which changes the cross-linking density of nitrogen-coordinated boroxines and the topology of the supramolecular thermosets. The mechanically strongest supramolecular thermosets with a molar ratio of Tri-PBA-PPG to Bi-PBA-PPG being 1:2 have a glass transition temperature of ∼36 °C, a tensile strength of ∼31.96 MPa, and a Young's modulus of ∼298.5 MPa. The high reversibility of nitrogen-coordinated boroxines and the flexibility of poly(propylene glycol) chains enable the supramolecular thermosets with the strongest mechanical strength to be highly efficiently healed at 55 °C and recycled under a pressure of 4 MPa at 60 °C to regain their original mechanical strength and integrity.