BRASSINOSTEROID-SIGNALING KINASE1 modulates MAP KINASE15 phosphorylation to confer powdery mildew resistance in Arabidopsis.

Perception of pathogen-associated molecular patterns (PAMPs) by plant cell surface-localized pattern-recognition receptors (PRRs) triggers the first line of plant innate immunity. In Arabidopsis thaliana, the receptor-like cytoplasmic kinase BRASSINOSTEROID-SIGNALING KINASE1 (BSK1) physically associates with PRR FLAGELLIN SENSING2 and plays an important role in defense against multiple pathogens. However, how BSK1 transduces signals to activate downstream immune responses remains elusive. Previously, through whole-genome phosphorylation analysis using mass spectrometry, we showed that phosphorylation of the mitogen-activated protein kinase (MAPK) MPK15 was affected in the bsk1 mutant compared with the wild-type plants. Here, we demonstrated that MPK15 is important for powdery mildew fungal resistance. PAMPs and fungal pathogens significantly induced the phosphorylation of MPK15 Ser-511, a key phosphorylation site critical for the functions of MPK15 in powdery mildew resistance. BSK1 physically associates with MPK15 and is required for basal and pathogen-induced MPK15 Ser-511 phosphorylation, which contributes to BSK1-mediated fungal resistance. Taken together, our data identified MPK15 as a player in plant defense against powdery mildew fungi and showed that BSK1 promotes fungal resistance in part by enhancing MPK15 Ser-511 phosphorylation. These results uncovered a mechanism of BSK1-mediated disease resistance and provided new insight into the role of MAPK phosphorylation in plant immunity.

Optineurin promotes myogenesis during muscle regeneration in mice by autophagic degradation of GSK3ß.

Skeletal muscle regeneration is essential for maintaining muscle function in injury and muscular disease. Myogenesis plays key roles in forming new myofibers during the process. Here, through bioinformatic screen for the potential regulators of myogenesis from 5 independent microarray datasets, we identify an overlapping differentially expressed gene (DEG) optineurin (OPTN). Optn knockdown (KD) delays muscle regeneration in mice and impairs C2C12 myoblast differentiation without affecting their proliferation. Conversely, Optn overexpression (OE) promotes myoblast differentiation. Mechanistically, OPTN increases nuclear levels of ß-catenin and enhances the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription activity, suggesting activation of Wnt signaling pathway. The activation is accompanied by decreased protein levels of glycogen synthase kinase 3ß (GSK3ß), a negative regulator of the pathway. We further show that OPTN physically interacts with and targets GSK3ß for autophagic degradation. Pharmacological inhibition of GSK3ß rescues the impaired myogenesis induced by Optn KD during muscle regeneration and myoblast differentiation, corroborating that GSK3ß is the downstream effector of OPTN-mediated myogenesis. Together, our study delineates the novel role of OPTN as a potential regulator of myogenesis and may open innovative therapeutic perspectives for muscle regeneration.

Camptothecin effectively treats obesity in mice through GDF15 induction.

Elevated circulating levels of growth differentiation factor 15 (GDF15) have been shown to reduce food intake and lower body weight through activation of hindbrain receptor glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) in rodents and nonhuman primates, thus endogenous induction of this peptide holds promise for obesity treatment. Here, through in silico drug-screening methods, we found that small molecule Camptothecin (CPT), a previously identified drug with potential antitumor activity, is a GDF15 inducer. Oral CPT administration increases circulating GDF15 levels in diet-induced obese (DIO) mice and genetic ob/ob mice, with elevated Gdf15 expression predominantly in the liver through activation of integrated stress response. In line with GDF15's anorectic effect, CPT suppresses food intake, thereby reducing body weight, blood glucose, and hepatic fat content in obese mice. Conversely, CPT loses these beneficial effects when Gdf15 is inhibited by a neutralizing antibody or AAV8-mediated liver-specific knockdown. Similarly, CPT failed to reduce food intake and body weight in GDF15's specific receptor GFRAL-deficient mice despite high levels of GDF15. Together, these results indicate that CPT is a promising anti-obesity agent through activation of GDF15-GFRAL pathway.

NUA positively regulates plant immunity by coordination with ESD4 to deSUMOylate TPR1 in Arabidopsis.

Nuclear pore complex (NPC) is composed of multiple nucleoporins (Nups). A plethora of studies have highlighted the significance of NPC in plant immunity. However, the specific roles of individual Nups are poorly understood. NUCLEAR PORE ANCHOR (NUA) is a component of NPC. Loss of NUA leads to an increase in SUMO conjugates and pleiotropic developmental defects in Arabidopsis thaliana. Herein, we revealed that NUA is required for plant defense against multiple pathogens. NUCLEAR PORE ANCHOR associates with the transcriptional corepressor TOPLESS-RELATED1 (TPR1) and contributes to TPR1 deSUMOylation. Significantly, NUA-interacting protein EARLY IN SHORT DAYS 4 (ESD4), a SUMO protease, specifically deSUMOylates TPR1. It has been previously established that the SUMO E3 ligase SAP AND MIZ1 DOMAIN-CONTAINING LIGASE 1 (SIZ1)-mediated SUMOylation of TPR1 represses the immune-related function of TPR1. Consistent with this notion, the hyper-SUMOylated TPR1 in nua-3 leads to upregulated expression of TPR1 target genes and compromised TPR1-mediated disease resistance. Taken together, our work uncovers a mechanism by which NUA positively regulates plant defense responses by coordination with ESD4 to deSUMOylate TPR1. Our findings, together with previous studies, reveal a regulatory module in which SIZ1 and NUA/ESD4 control the homeostasis of TPR1 SUMOylation to maintain proper immune output.

The selective sponging of miRNAs by OIP5-AS1 regulates metabolic reprogramming of pyruvate in adenoma-carcinoma transition of human colorectal cancer.

RNA interactomes and their diversified functionalities have recently benefited from critical methodological advances leading to a paradigm shift from a conventional conception on the regulatory roles of RNA in pathogenesis. However, the dynamic RNA interactomes in adenoma-carcinoma sequence of human CRC remain unexplored. The coexistence of adenoma, cancer, and normal tissues in colorectal cancer (CRC) patients provides an appropriate model to address this issue. Here, we adopted an RNA in situ conformation sequencing technology for mapping RNA-RNA interactions in CRC patients. We observed large-scale paired RNA counts and identified some unique RNA complexes including multiple partners RNAs, single partner RNAs, non-overlapping single partner RNAs. We focused on the antisense RNA OIP5-AS1 and found that OIP5-AS1 could sponge different miRNA to regulate the production of metabolites including pyruvate, alanine and lactic acid. Our findings provide novel perspectives in CRC pathogenesis and suggest metabolic reprogramming of pyruvate for the early diagnosis and treatment of CRC.

A novel splicing mutation DNAH5 c.13,338 + 5G > C is involved in the pathogenesis of primary ciliary dyskinesia in a family with primary familial brain calcification.

BACKGROUND: Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcification in the basal ganglia and other brain regions. PFBC can be inherited in an autosomal dominant or recessive manner. A family with PCD caused by a DNAH5 compound heterozygous variant and PFBC caused by a MYORG homozygous variant was analyzed. METHODS: In this study, we recruited three generations of Han families with primary ciliary dyskinesia combined with primary familial brain calcification. Their clinical phenotype data were collected, next-generation sequencing was performed to screen suspected pathogenic mutations in the proband and segregation analysis of families was carried out by Sanger sequencing. The mutant and wild-type plasmids were constructed and transfected into HEK293T cells instantaneously, and splicing patterns were detected by Minigene splicing assay. The structure and function of mutations were analyzed by bioinformatics analysis. RESULTS: The clinical phenotypes of the proband (II10) and his sister (II8) were bronchiectasis, recurrent pulmonary infection, multiple symmetric calcifications of bilateral globus pallidus and cerebellar dentate nucleus, paranasal sinusitis in the whole group, and electron microscopy of bronchial mucosa showed that the ciliary axoneme was defective. There was also total visceral inversion in II10 but not in II8. A novel splice variant C.13,338 + 5G > C and a frameshift variant C.4314delT (p. Asn1438lysfs *10) were found in the DNAH5 gene in proband (II10) and II8. c.347_348dupCTGGCCTTCCGC homozygous insertion variation was found in the MYORG of the proband. The two pathogenic genes were co-segregated in the family. Minigene showed that DNAH5 c.13,338 + 5G > C has two abnormal splicing modes: One is that part of the intron bases where the mutation site located is translated, resulting in early translation termination of DNAH5; The other is the mutation resulting in the deletion of exon76. CONCLUSIONS: The newly identified DNAH5 splicing mutation c.13,338 + 5G > C is involved in the pathogenesis of PCD in the family, and forms a compound heterozygote with the pathogenic variant DNAH5 c.4314delT lead to the pathogenesis of PCD.

Unlocking Single Particle Anisotropy in Real-Time for Photoelectrochemistry Processes at the Nanoscale.

The key to rationally and rapidly designing high-performance materials is the monitoring and comprehension of dynamic processes within individual particles in real-time, particularly to gain insight into the anisotropy of nanoparticles. The intrinsic property of nanoparticles typically varies from one crystal facet to the next under realistic working conditions. Here, we introduce the operando collision electrochemistry to resolve the single silver nanoprisms (Ag NPs) anisotropy in photoelectrochemistry. We directly identify the effect of anisotropy on the plasmonic-assisted electrochemistry at the single NP/electrolyte interface. The statistical collision frequency shows that heterogeneous diffusion coefficients among crystal facets facilitate Ag NPs to undergo direction-dependent mass transfer toward the gold ultramicroelectrode. Subsequently, the current amplitudes of transient events indicate that the anisotropy enables variations in dynamic interfacial electron transfer behaviors during photothermal processes. The results presented here demonstrate that the measurement precision of collision electrochemistry can be extended to the sub-nanoparticle level, highlighting the potential for high-throughput material screening with comprehensive kinetics information at the nanoscale.

Electrochemical Monitoring of Real-Time Vesicle Dynamics Induced by Tau in a Confined Nanopipette.

The microtubule-associated protein tau participates in neurotransmission regulation via its interaction with synaptic vesicles (SVs). The precise nature and mechanics of tau's engagement with SVs, especially regarding alterations in vesicle dynamics, remain a matter of discussion. We report an electrochemical method using a synapse-mimicking nanopipette to monitor vesicle dynamics induced by tau. A model vesicle of ~30 nm is confined within a lipid-modified nanopipette orifice with a comparable diameter to mimic the synaptic lipid environment. Both tau and phosphorylated tau (p-tau) present two-state dynamic behavior in this biomimetic system, showing typical ionic current oscillation, induced by lipid-tau interaction. The results indicate that p-tau has a stronger affinity to the lipid vesicles in the confined environment, blocking the vesicle movement to a higher degree. Taken together, this method bridges a gap for sensing synaptic vesicle dynamics in a confined lipid environment, mimicking vesicle movement near the synaptic membrane. These findings contribute to understanding how different types of tau protein regulate synaptic vesicle motility and to underlying its functional and pathological behaviours in disease.

Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice.

Obesity leads to multiple health problems, including diabetes, fatty liver, and even cancer. Here, we report that urolithin A (UA), a gut-microflora-derived metabolite of pomegranate ellagitannins (ETs), prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse effects. UA treatment increases energy expenditure (EE) by enhancing thermogenesis in brown adipose tissue (BAT) and inducing browning of white adipose tissue (WAT). Mechanistically, UA-mediated increased thermogenesis is caused by an elevation of triiodothyronine (T3) levels in BAT and inguinal fat depots. This is also confirmed in UA-treated white and brown adipocytes. Consistent with this mechanism, UA loses its beneficial effects on activation of BAT, browning of white fat, body weight control, and glucose homeostasis when thyroid hormone (TH) production is blocked by its inhibitor, propylthiouracil (PTU). Conversely, administration of exogenous tetraiodothyronine (T4) to PTU-treated mice restores UA-induced activation of BAT and browning of white fat and its preventive role on high-fat diet (HFD)-induced weight gain. Together, these results suggest that UA is a potent antiobesity agent with potential for human clinical applications.

Boosting Antibacterial Photodynamic Therapy in a Nanosized Zr MOF by the Combination of Ag NP Encapsulation and Porphyrin Doping.

Antibacterial photodynamic therapy (aPDT) is regarded as one of the most promising antibacterial therapies due to its nonresistance, noninvasion, and rapid sterilization. However, the development of antibacterial materials with high aPDT efficacy is still a long-standing challenge. Herein, we develop an effective antibacterial photodynamic composite UiO-66-(SH)2@TCPP@AgNPs by Ag encapsulation and 4,4',4″,4‴-(porphine-5,10,15,20-tetrayl)tetrakis(benzoic acid) (TCPP) dopant. Through a mix-and-match strategy in the self-assembly process, 2,5-dimercaptoterephthalic acid containing -SH groups and TCPP were uniformly decorated into the UiO-66-type framework to form UiO-66-(SH)2@TCPP. After Ag(I) impregnation and in situ UV light reduction, Ag NPs were formed and encapsulated into UiO-66-(SH)2@TCPP to get UiO-66-(SH)2@TCPP@AgNPs. In the resulting composite, both Ag NPs and TCPP can effectively enhance the visible light absorption, largely boosting the generation efficiency of reactive oxygen species. Notably, the nanoscale size enables it to effectively contact and be endocytosed into bacteria. Consequently, UiO-66-(SH)2@TCPP@AgNPs show a very high aPDT efficacy against Gram-negative and Gram-positive bacteria as well as drug-resistant bacteria (MRSA). Furthermore, the Ag NPs were firmly anchored at the framework by the high density of -SH moieties, avoiding the cytotoxicity caused by the leakage of Ag NPs. By in vitro experiments, UiO-66-(SH)2@TCPP@AgNPs show a very high antibacterial activity and good biocompatibility as well as the potentiality to promote cell proliferation.

Smart Hairpins@MnO2 Nanosystem Enables Target-Triggered Enzyme-Free Exponential Amplification for Ultrasensitive Imaging of Intracellular MicroRNAs in Living Cells.

Sensitive and specific imaging of microRNA (miRNA) in living cells is of great value for disease diagnosis and monitoring. Hybridization chain reaction (HCR) and DNAzyme-based methods have been considered as powerful tools for miRNA detection, with low efficient intracellular delivery and limited amplification efficiency. Herein, we propose a Hairpins@MnO2 nanosystem for intracellular enzyme-free exponential amplification for miRNA imaging. The enzyme-free exponential amplification is based on the synergistic cross-activation between HCR and DNAzymes. The MnO2 nanosheets were employed as the carrier of three kinds of hairpin DNA probes and further provided appropriate Mn2+ as DNAzyme cofactors in the living cell. Upon entering cells and in the presence of highly expressed glutathione (GSH) in tumors, MnO2 is reduced to release Mn2+ and the three kinds of hairpin DNA probes. In the presence of target miRNA, the released hairpin DNA H1 and H2 probes self-assemble via HCR into the wire-shaped active Mn2+-based DNAzymes which further catalyze the cleavage of H3 to generate numerous new triggers to reversely stimulate HCR amplifiers, thus offering tremendously amplified Förster resonance energy transfer readout. The method has a detection limit of 33 fM, which is 2.4 × 104 times lower than that of the traditional HCR system. The developed method also has a high specificity; even miRNAs with a single base difference can be distinguished. Live cell imaging experiments confirmed that this Hairpins@MnO2 nanosystem allows accurate differentiation of miRNA expression of cancer cells and normal cells. The method holds great potential in biological research of nucleic acids.

Human brucellosis and fever of unknown origin.

BACKGROUND: Human brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted. METHODS: We retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records. RESULTS: The percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P < 0.05), and 80% of the patients had a clear history of exposure to cattle and sheep. Moreover, 19 (54%) cases were hospitalized with FUO, among which the patients with epidemiological histories were significantly more than those without (P < 0.05). The incidence of toxic hepatitis in FUO patients was higher than that in non-FUO patients (89% vs. 50%, P < 0.05). Meanwhile, the misdiagnosis rate was considerably higher in the FUO group than in the non-FUO group (100% vs. 63%; P < 0.05). CONCLUSION: Brucellosis is predominantly FUO admission in a non-endemic area of China, accompanied by irregular fever and toxic hepatitis. Careful examination of the epidemiological history and timely improvement of blood and bone marrow cultures can facilitate early diagnosis and prevent misdiagnosis.

Store-operated calcium entry-associated regulatory factor regulates airway inflammation and airway remodeling in asthma mice models.

Store-operated calcium entry (SOCE) is involved in the pathogenesis of airway inflammation and remodeling in asthma. Store-operated calcium entry-associated regulatory factor (SARAF) can downregulate SOCE. We sought to investigate the role of SARAF in the regulation of airway inflammation and remodeling in asthma mice models, as well as in the functional regulation of human airway smooth muscle cells (hASMCs). Balb/c mice were sensitized and challenged with ovalbumin to establish the asthma mice models. Mice were transfected with lentivirus, which expressed the SARAF gene + GFP (green fluorescence protein) or the negative control gene + GFP. Airway resistance was measured with the animal pulmonary function system. Airway inflammation and remodeling were evaluated via histological staining. In vitro cultured hASMCs were transfected with scrambled small interfering RNA (siRNA) or SARAF-specific siRNA, respectively. The proliferation, migration rate, hypertrophy, and SOCE activity of hASMCs were examined with Cell Counting Kit-8, wound healing test, bright field imaging, and Ca2+ fluorescence imaging, respectively. SARAF expression was measured by quantitative real-time PCR. Asthma mice models showed decreased SARAF mRNA expression in the lungs. SARAF overexpression attenuated airway inflammation, resistance, and also remodeling. Downregulation of SARAF expression with siRNA promoted the proliferation, migration, hypertrophy, and SOCE activity in hASMCs. SARAF plays a protective role against airway inflammation and remodeling in asthma mice models by blunting SOCE; SARAF may also be a functional regulating factor of hASMCs.

Mitochondrial aconitase controls adipogenesis through mediation of cellular ATP production.

Mitochondrial aconitase (Aco2) catalyzes the conversion of citrate to isocitrate in the TCA cycle, which produces NADH and FADH2, driving synthesis of ATP through OXPHOS. In this study, to explore the relationship between adipogenesis and mitochondrial energy metabolism, we hypothesize that Aco2 may play a key role in the lipid synthesis. Here, we show that overexpression of Aco2 in 3T3-L1 cells significantly increased lipogenesis and adipogenesis, accompanied by elevated mitochondrial biogenesis and ATP production. However, when ATP is depleted by rotenone, an inhibitor of the respiratory chain, the promotive role of Aco2 in adipogenesis is abolished. In contrast to Aco2 overexpression, deficiency of Aco2 markedly reduced lipogenesis and adipogenesis, along with the decreased mitochondrial biogenesis and ATP production. Supplementation of isocitrate efficiently rescued the inhibitory effect of Aco2 deficiency. Similarly, the restorative effect of isocitrate was abolished in the presence of rotenone. Together, these results show that Aco2 sustains normal adipogenesis through mediating ATP production, revealing a potential mechanistic link between TCA cycle enzyme and lipid synthesis. Our work suggest that regulation of adipose tissue mitochondria function may be a potential way for combating abnormal adipogenesis related diseases such as obesity and lipodystrophy.

Rearranged Diels-Alder Adducts and Prenylated Flavonoids as Potential PTP1B Inhibitors from Morus nigra.

Two novel rearranged Diels-Alder adducts, morunigrines A (1) and B (2), and four new prenylated flavonoids, morunigrols A-D (3-6), were isolated from the twigs of Morus nigra, together with four known prenylated phenolic compounds, including two flavonoids (7 and 8) and two 2-arylbenzofurans (9 and 10). Morunigrines A (1) and B (2) are a novel class of Diels-Alder adducts with unprecedented carbon skeletons featuring a rearranged chalcone-stilbene/2-arylbenzofuran core decorated with a unique methylbiphenyl moiety. The structures of the new compounds were assigned by analysis of spectroscopic data. The absolute configuration of compound 6 was determined by the measurement of specific rotation. A plausible biogenetic pathway for 1 and 2 is also proposed. Compounds 1 and 2 exhibited more potent protein tyrosine phosphatase 1B inhibitory activity with IC50 values of 1.8 ± 0.2 and 1.3 ± 0.3 µM, respectively, than that of the positive control oleanolic acid (IC50, 2.5 ± 0.1 µM).

Genome-wide analysis and prediction of genes involved in the biosynthesis of polysaccharides and bioactive secondary metabolites in high-temperature-tolerant wild Flammulina filiformis.

BACKGROUND: Flammulina filiformis (previously known as Asian F. velutipes) is a popular commercial edible mushroom. Many bioactive compounds with medicinal effects, such as polysaccharides and sesquiterpenoids, have been isolated and identified from F. filiformis, but their biosynthesis and regulation at the molecular level remains unclear. In this study, we sequenced the genome of the wild strain F. filiformis Liu355, predicted its biosynthetic gene clusters (BGCs) and profiled the expression of these genes in wild and cultivar strains and in different developmental stages of the wild F. filiformis strain by a comparative transcriptomic analysis. RESULTS: We found that the genome of the F. filiformis was 35.01 Mb in length and harbored 10,396 gene models. Thirteen putative terpenoid gene clusters were predicted and 12 sesquiterpene synthase genes belonging to four different groups and two type I polyketide synthase gene clusters were identified in the F. filiformis genome. The number of genes related to terpenoid biosynthesis was higher in the wild strain (119 genes) than in the cultivar strain (81 genes). Most terpenoid biosynthesis genes were upregulated in the primordium and fruiting body of the wild strain, while the polyketide synthase genes were generally upregulated in the mycelium of the wild strain. Moreover, genes encoding UDP-glucose pyrophosphorylase and UDP-glucose dehydrogenase, which are involved in polysaccharide biosynthesis, had relatively high transcript levels both in the mycelium and fruiting body of the wild F. filiformis strain. CONCLUSIONS: F. filiformis is enriched in a number of gene clusters involved in the biosynthesis of polysaccharides and terpenoid bioactive compounds and these genes usually display differential expression between wild and cultivar strains, even in different developmental stages. This study expands our knowledge of the biology of F. filiformis and provides valuable data for elucidating the regulation of secondary metabolites in this unique F. filiformis strain.

Pulmonary pathology of early-phase COVID-19 pneumonia in a patient with a benign lung lesion.

AIMS: An ongoing outbreak of 2019 novel coronavirus (CoV) disease (COVID-19), caused by severe acute respiratory syndrome (SARS) CoV-2, has been spreading in multiple countries. One of the reasons for the rapid spread is that the virus can be transmitted from infected individuals without symptoms. Revealing the pathological features of early-phase COVID-19 pneumonia is important for understanding of its pathogenesis. The aim of this study was to explore the pulmonary pathology of early-phase COVID-19 pneumonia in a patient with a benign lung lesion. METHODS AND RESULTS: We analysed the pathological changes in lung tissue from a 55-year-old female patient with early-phase SARS-CoV-2 infection. In this case, right lower lobectomy was performed for a benign pulmonary nodule. Detailed clinical, laboratory and radiological data were also examined. This patient was confirmed to have preoperative SARS-CoV-2 infection by the use of real-time reverse transcription polymerase chain reaction and RNA in-situ hybridisation on surgically removed lung tissues. Histologically, COVID-19 pneumonia was characterised by exudative inflammation. The closer to the visceral pleura, the more severe the exudation of monocytes and lymphocytes. Perivascular inflammatory infiltration, intra-alveolar multinucleated giant cells, pneumocyte hyperplasia and intracytoplasmic viral-like inclusion bodies were seen. However, fibrinous exudate and hyaline membrane formation, which were typical pulmonary features of SARS pneumonia, were not evident in this case. Immunohistochemical staining results showed an abnormal accumulation of CD4+ helper T lymphocytes and CD163+ M2 macrophages in the lung tissue. CONCLUSION: The results highlighted the pulmonary pathological changes of early-phase SARS-CoV-2 infection, and suggested a role of immune dysfunction in the pathogenesis of COVID-19 pneumonia.

Serum Procalcitonin, White Blood Cell and Hypersensitive C-reactive Protein Combined with Age Established a New Prediction Model in Predicting ICU Admission in Adult Community-Acquired Pneumonia (CAP) Patients.

BACKGROUND: CAP is the most common cause of death in infectious diseases in developing countries, while also an important cause of death and morbidity in developed countries. In recent years, CURB-65 (or CRB-65) and pneumonia severity index (PSI) scoring systems have been widely used in the prognosis scoring system of CAP. However, each of them has some shortcomings in predicting ICU admission in CAP patients. The aim of this study is to analyze serum inflammatory biomarkers combined age to established a new prediction model in predicting ICU admission in CAP patients. METHODS: This is a retrospective study. The enrolled CAP patients received serum inflammatory biomarker tests, including procalcitonin (PCT), white blood cell count (WBC), hypersensitive C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR). Body temperature and age were also recorded. The main outcome measures were ICU admission. Univariate analysis and binary logistic regression analysis were used to explore the in-dependent risk factors which could be components of a new predicting model for ICU admission in CAP patients. Receiver operating characteristic curves (ROC) were used to evaluate the sensitivity and specificity of the new model, which consisted of the combination of all independent risk factors in predicting the main outcomes. RESULTS: Initially, 246 CAP patients were admitted to general wards, 61 of whom were subsequently transferred to ICU (61/246). Age, PCT, WBC, and hs-CRP were independent risk factors for subsequent admission to ICU for CAP patients in general wards. The AUC of the ROC curve of new prediction model (the joint model consists of age, PCT, WBC, and hs-CRP) was 0.93 (95% CI 0.85 - 0.96), the sensitivity and specificity were 85.2% and 88.1%, respectively. CONCLUSIONS: Serum inflammatory biomarkers combined age have high specificity and sensitivity in predicting ICU admission in adult CAP patients.

Speedy, Specific, Synchronous Sensing Platforms with Ruthenium Complexes for Multiplexed MicroRNA Detection.

Inspired by our previous study on Ru(II)-based compounds for the construction of a sensing platform toward detection of microRNA-185 (miR-185), we herein report new analytical platforms based on two additional Ru(II) compounds, Ru 2 and Ru 3, with larger aromatic ring structures and richer hydrogen bond donor/acceptor sites in comparison to the previously reported Ru 1, as simultaneous detection agents for miR-221/222, which work together to promote the occurrence and development of breast cancer. Molecular simulation docking was first used to predict the nucleic acid sequence binding affinity toward Ru(II) compounds to guide the experiment. The experimental results reveal that Ru 2 and Ru 3 can form a P-DNA@Ru sensing platform with the introduction of carboxyfluorescein (FAM)/5-carboxy-X-rhodamine (ROX) tagged single-chained probe DNA (P-DNA), to realize the discernment of the complementary P-DNA sequence of miR-221/222, giving the limit of detection (LOD) at the nanomolar level with a specific and speedy response. The detection mechanism was verified by binding capacity, luminescence decay, and fluorescence anisotropy (FA), as well as the polyacrylamide gel electrophoresis (PAGE) technique. Furthermore, the formed P-DNA@Ru 2/3 systems could be prepared for the simultaneous and synchronous detection of miR-221/222 sequences, improving the detection efficiency in a time-efficient manner and satisfying the speedy diagnosis requirements of current medical practive.

Neutrophil-to-Lymphocyte Ratio Improves the Accuracy and Sensitivity of Pneumonia Severity Index in Predicting 30-Day Mortality of CAP Patients.

BACKGROUND: The pneumonia severity index (PSI) scoring system is one of the tools used to evaluate and predict the prognosis of patients with community-acquired pneumonia (CAP). Although PSI has been widely used in clinical studies of pneumonia, it is still rare to combine it with blood indexes to predict the prognosis of pneumonia. Neutrophil-to-lymphocyte ratio (NLR) is a promising candidate predictor of mortality in CAP patients. The aim of this study was to investigate the efficacy of pneumonia severity index combined with NLR in predicting 30-day mortality in CAP patients. METHODS: We conducted a retrospective study. We analyzed data on 400 non-immune individuals over the age of 18 in this study. All patients received blood routine measurement and PSI score calculation after admission. The primary outcome measures were mortality and survival in CAP patients. The sensitivity and specificity of PSI score, NLR, and the combination of PSI score and NLR in predicting 30-day mortality were assessed using the subject operating characteristic curve (ROC). RESULTS: Data from 400 patients were analyzed, in which the 30-day mortality was 10.5% (42/400). The AUC of NLR and PSI in predicting 30-day mortality of CAP patients were 0.81 (95% CI 0.73 - 0.89) and 0.94 (95% CI 0.90 - 0.98), respectively, with statistically significant differences (p = 0.00). The sensitivity and specificity of NLR were 0.80 and 0.7, respectively. The sensitivity and specificity of PSI were 0.78 and 0.94, respectively. The combined AUC of the two indicators for predicting death in CAP patients was 0.95 (95% CI 0.92 - 0.99), and the sensitivity and specificity were 0.85 and 0.94, respectively. CONCLUSIONS: Neutrophil-to-lymphocyte ratio improves the accuracy and sensitivity of the pneumonia severity index in predicting 30-day mortality of CAP patients.