Prediction of Proximal Junctional Kyphosis and Failure After Corrective Surgery for Adult Spine Deformity: An MRI-Based Model Combining Bone and Paraspinal Muscle Quality Metrics.

BACKGROUND: Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are common complications observed after adult spinal deformity (ASD) surgery and major cause for unplanned reoperations. In addition to spinal alignment, osteoporosis and paraspinal muscle (PSM) degeneration are reportedly indispensable factors that account for PJK/PJF. PURPOSE: To investigate the utility of the preoperative risk assessment model using MRI-based skeletomuscular metrics in predicting PJK and/or PJF(PJK/PJF) after ASD correction. STUDY DESIGN: Retrospective Case-Control study. PATIENT SAMPLE: Consecutive series of 149 patients at a single academic institution. OUTCOME MEASURES: MRI based measurements of vertebral bone quality at upper instrumented vertebra (VBQ-U) score and fat infiltration rate (FI%) of paraspinal muscle (PSM). METHODS: We performed a retrospective analysis of patients with ASD who underwent ≥5-segment fusion. The vertebral bone quality (VBQ) scoring system was used to assess the bone quality. The PSM quality including FI% and cross-sectional area (CSA) were evaluated. Multivariate logistic regression was performed to determine potential risk factors of PJK/PJF. RESULTS: Of 149 patients who underwent ASD surgery, PJK/PJF was found in 45(30.2%). Mean VBQ-U scores were 3.45 ± 0.64 and 3.00 ± 0.56 for patients with and without PJK/PJF (P<0.001). Mean FI% of PSM(L3/L4) was 27.9 ± 12.8 and 20.7 ± 13.3 for patients with and without PJK/PJF (P<0.001). On multivariate analysis, the VBQ-U score and FI% of PSM were significant independent predictors of PJK/PJF. The AUC for the novel risk assessment model is 0.806, with a predictive accuracy of 86.7%. CONCLUSION: In patients undergoing ASD correction, paraspinal muscle and vertebral bone quality significantly outweigh radiographic alignment parameters in predicting PJK/PJF. The MRI-based risk assessment model offers a valuable tool for early assessing individualized risk information for PJK/PJF.

Suppression of Zinc Dendrite Growth by Enhanced Polyacrylamide Gel Electrolytes in Zinc-ion Battery.

Aqueous zinc-ion batteries have become a promising energy storage battery due to high theoretical specific capacity, abundant zinc resources and low cost. However, zinc dendrite growth and hydrogen evolution reaction limit their application. This study aims to improve the cycling performance and stability of aqueous zinc-ion batteries by improving the gel electrolyte. Polyacrylamide (PAM) is selected as the base material of the gel electrolyte, which has good stability and safety, but the water retention capacity, Zn2+ migration number, and ionic conductivity of PAM are low, which affects the long-term stability of the battery. In response to these problems, we optimized PAM by chemical cross-linking method, and formed an enhanced PAM gel by adding disodium citrate dihydrate (SC). Experimental results show that the introduction of an appropriate amount of SC in the enhanced PAM gel electrolyte can significantly improve its electrochemical performance. The zinc-ion symmetric battery achieved a stable cycle of more than 2100 hours at a current density of 0.5 mA cm-2, which is mainly attributed to the inhibitory effect of the enhanced PAM gel on zinc dendrite growth and hydrogen evolution reaction. This study provides a new direction for the development and application of flexible zinc-ion batteries.

Photocatalytic deuterocarboxylation of alkynes with oxalate.

Herein, a catalytic photoredox-neutral strategy for alkyne deuterocarboxylation with tetrabutylammonium oxalate as the carbonyl source and D2O as the deuteration agent was described. For the first time, the oxalic salt acted as both the reductant and carbonyl source through single electron transfer and subsequential homolysis of the C-C bond. The strongly reductive CO2 radical anion species in situ generated from oxalate played significant roles in realizing the global deuterocarboxylation of terminal and internal alkynes to access various tetra- and tri-deuterated aryl propionic acids with high yields and deuteration ratios.

The effects of BMP2 and the mechanisms involved in the invasion and angiogenesis of IDH1 mutant glioma cells.

PURPOSE: This study investigated the effect of an isocitrate dehydrogenase 1 (IDH1) mutation (mutIDH1) on the invasion and angiogenesis of human glioma cells. METHODS: Doxycycline was used to induce the expression of mutIDH1 in glioma cells. Transwell and wound healing assays were conducted to assess glioma cell migration and invasion. Western blotting and cell immunofluorescence were used to measure the expression levels of various proteins. The influence of bone morphogenetic protein 2 (BMP2) on invasion, angiogenesis-related factors, BMP2-related receptor expression, and changes in Smad signaling pathway-related proteins were evaluated after treatment with BMP2. Differential gene expression and reference transcription analysis were performed. RESULTS: Successful infection with recombinant lentivirus expressing mutIDH1 was demonstrated. The IDH1 mutation promoted glioma cell migration and invasion while positively regulating the expression of vascularization-related factors and BMP2-related receptors. BMP2 exhibited a positive regulatory effect on the migration, invasion, and angiogenesis of mutIDH1-glioma cells, possibly mediated by BMP2-induced alterations in Smad signaling pathway-related factors.After BMP2 treatment, the differential genes of MutIDH1-glioma cells are closely related to the regulation of cell migration and cell adhesion, especially the regulation of Smad-related proteins. KEGG analysis confirmed that it was related to BMP signaling pathway and TGF-ß signaling pathway and cell adhesion. Enrichment analysis of gene ontology and genome encyclopedia further confirmed the correlation of these pathways. CONCLUSION: Mutation of isocitrate dehydrogenase 1 promotes the migration, invasion, and angiogenesis of glioma cells, through its effects on the BMP2-driven Smad signaling pathway. In addition, BMP2 altered the transcriptional patterns of mutIDH1 glioma cells, enriching different gene loci in pathways associated with invasion, migration, and angiogenesis.

Plant natural product-based pesticides in crop protection: semi-synthesis, mono-crystal structures and agrochemical activities of osthole ester derivatives, and study of their toxicology against Tetranychus cinnabarinus (Boisduval).

BACKGROUND: Owing to large amounts of synthetic pesticides being extensively and unreasonably used for crop protection, currently, resistance and negative impacts on human health and environment safety have appeared. Therefore, development of potential pesticide candidates is highly urgent. Herein, a series of ester derivatives of osthole were designed and synthesized as pesticidal agents. RESULTS: Six spatial configurations of 4'-(p-toluenoyloxy)osthole (4b), 4'-(m-fluorobenzoyloxy)osthole (4f), 4'-(p-fluorophenylacetyloxy)osthole (4m), 4'-(3'',4''-methylenedioxybenzoyloxy)osthole (4q), 4'-formyloxyosthole (4u) and 4'-acetyloxyosthole (4v) were determined by X-ray mono-crystal diffraction. Compounds 4b, 4'-(p-chlorobenzoyloxy)osthole (4g), 4'-(m-chlorobenzoyloxy)osthole (4h), 4'-(p-bromobenzoyloxy)osthole (4i) and 4'-(2''-chloropyridin-3''-ylcarbonyloxy)osthole (4p) showed higher insecticidal activity than toosendanin against Mythimna separata Walker; notably, compound 4b displayed 1.8 times insecticidal activity of the precursor osthole. Against Tetranychus cinnabarinus Boisduval, compounds 4g and 4h showed 3.3 and 2.6 times acaricidal activity of osthole, and good control effects in the glasshouse. Scanning electron microscopy assay demonstrated that compound 4g can damage the cuticle layer of T. cinnabarinus resulting in death. CONCLUSION: Compounds 4g and 4h can be further studied as lead pesticidal agents for the management of M. separata and T. cinnabarinus. These results will pave the way for application of osthole derivatives as agrochemicals. © 2024 Society of Chemical Industry.

[Effects of Sophora japonica extract on alveolar bone mass in ovariectomized osteoporosis mice].

PURPOSE: To investigate the effect of Sophora japonica extract on alveolar bone mass in ovariectomized osteoporosis mice. METHODS: Six-week-old female non-pregnant wild-type C57BL/6J mice were randomly divided into sham operation group, ovariectomy(OVX) group and OVX+Sophora japonica extract group. Ovaries of the mice in the OVX group and the OVX+Sophora japonica extract group were removed, and the mice in the OVX+Sophora japonica extract group were treated by Sophora japonica extract at a dose of 150 mg/kg, three times a week for 4 weeks; while mice of the other two groups were given an equal volume of normal saline at the same time. Body weight was measured 3 times a week, and the micro-parameters of alveolar bone were detected by Micro-CT after 4 weeks. The data were analyzed by GraphPad Prism 9 software. RESULTS: Compared with the sham-operated group, the trabecular bone parameters of the alveolar bone in the OVX group were significantly decreased 1 month after operation (P＜0.05). One month after intervention with Sophora japonica extract, alveolar bone mineral density (BMD), trabecular number (Tb.N) and trabecular separation(Tb.Sp) in OVX mice was significantly rescued, with no significant difference compared to the sham surgery group(P＞0.05); but bone volume fraction(BV/TV) and trabecular thickness (Tb.Th) had not completely recovered to the levels of the sham-operated group(P＜0.05). CONCLUSIONS: Sophora japonica extract can effectively increase the alveolar bone mass reduced by estrogen deficiency and may be used as one of the potential drugs for the treatment of menopausal alveolar bone osteoporosis.

Machine learning-based analysis and prediction of meteorological factors and urban heatstroke diseases.

Introduction: Heatstroke is a serious clinical condition caused by exposure to high temperature and high humidity environment, which leads to a rapid increase of the core temperature of the body to more than 40°C, accompanied by skin burning, consciousness disorders and other organ system damage. This study aims to analyze the effect of meteorological factors on the incidence of heatstroke using machine learning, and to construct a heatstroke forecasting model to provide reference for heatstroke prevention. Methods: The data of heatstroke incidence and meteorological factors in a city in South China from May to September 2014-2019 were analyzed in this study. The lagged effect of meteorological factors on heatstroke incidence was analyzed based on the distributed lag non-linear model, and the prediction model was constructed by using regression decision tree, random forest, gradient boosting trees, linear SVRs, LSTMs, and ARIMA algorithm. Results: The cumulative lagged effect found that heat index, dew-point temperature, daily maximum temperature and relative humidity had the greatest influence on heatstroke. When the heat index, dew-point temperature, and daily maximum temperature exceeded certain thresholds, the risk of heatstroke was significantly increased on the same day and within the following 5 days. The lagged effect of relative humidity on the occurrence of heatstroke was different with the change of relative humidity, and both excessively high and low environmental humidity levels exhibited a longer lagged effect on the occurrence of heatstroke. With regard to the prediction model, random forest model had the best performance of 5.28 on RMSE and dropped to 3.77 after being adjusted. Discussion: The incidence of heatstroke in this city is significantly correlated with heat index, heatwave, dew-point temperature, air temperature and zhongfu, among which the heat index and dew-point temperature have a significant lagged effect on heatstroke incidence. Relevant departments need to closely monitor the data of the correlated factors, and adopt heat prevention measures before the temperature peaks, calling on citizens to reduce outdoor activities.

Enhancing interfacial electron transfer through PANI electron bridge for tailoring dynamic reconstruction and achieving high-performance water oxidation.

Tailoring the dynamic reconstruction of transition metal compounds into highly active oxyhydroxides through surface electron state modification is crucial for advancing water oxidation, yet remains a formidable challenge. In this study, a unique polyaniline (PANI) electron bridge was integrated into the metal-organic frameworks (MOFs)/layer double hydroxides (LDHs) heterojunction to expedite electron transfer from MOFs to LDHs, facilitating electron accumulation at the metal sites within MOF and electron-deficient LDHs. This configuration promotes the surface dynamic reconstruction of LDHs into highly active oxyhydroxides while safeguarding the MOF from corrosion in harsh environments over extended periods. The optimized electronic structure modification of both MOFs and LDHs enhances reaction kinetics. The superior MIL-88B(Fe)@PANI@NiCo LDH catalyst achieved 10 mA∙cm-2 at an overpotential of 202 mV and demonstrated stable operation for 120 h at this current density. This research introduces an innovative approach for guiding electron transfer and dynamic catalyst reconstruction by constructing a PANI electron bridge, potentially paving the way for more efficient catalytic systems.

Effect of Nitrogen on Precipitate Characteristics and Pitting Resistance of Martensitic Stainless Steel.

High-carbon-chromium martensitic stainless steel (MSS) is widely used in many fields due to its excellent mechanical properties, while the coarse eutectic carbide in MSS deteriorates corrosion resistance. In this work, nitrogen was added to the MSS to improve corrosion resistance. The effects of nitrogen on the microstructure and corrosion resistance of MSS were systematically studied. The results showed that the addition of nitrogen promoted the development of Cr2N and reversed austenite, effectively inhibiting the formation of δ-ferrite. Therefore, the durability of the passivation film was improved, the passivation zone was expanded, and the susceptibility to metastable pitting was decreased. As a consequence, nearly two orders of magnitude have been achieved in the pitting potential (Epit) of MSS containing nitrogen, and the polarization resistance value (Rp) has gone up from 4.05 kΩ·cm2 to 1.24 × 102 kΩ·cm2. This means that in a corrosive environment, nitrogen-treated MSS stainless steel is less likely to form pitting pits, which further extends the service life of the material.

Enhanced Enantioselective Discrimination Regulated by Achiral Ligands in Chiral Metal-Organic Frameworks.

Enantioselective recognition is a fundamental property of chiral linkers in chiral metal-organic frameworks (CMOFs). However, clarifying the efficient enantioselective discrimination tailored by achiral linkers remains challenging to explain the chiral recognition mechanism and efficiency. Here, two CMOFs ([Zn2(l-Phe)2(bpa)2]n and [Zn2(l-Phe)2(bpe)2]n) with the completely different enantioselective recognition are synthesized from different nonchiral ligands and the same chiral ligands. The enantioselective recognition of CMOF is undoubtedly related to l-Phe, which differs in the hydrogen bonding to the Trp enantiomer. However, the electrochemical signals are weak and undifferentiated. [Zn2(l-Phe)2(bpe)2]n produces a flattened coplanar conformation with the -C═C- tether in the achiral ligand. The flattened achiral bpee ligand and its surrounding chiral phenylalanine molecules interact through multiple π-π stacking and hydrogen bonding, which together create a chiral sensor that facilitates the recognition of l-Trp. However, [Zn2(l-Phe)2(bpa)2]n produces a stepped conformation due to the -C-C- tether in the achiral ligand; despite the recognition effect of bpea, the recognition is unsatisfactory. Therefore, the chiral recognition of the two CMOFs stems from the synergistic effect between chiral and achiral ligands. This work shows that nonchiral ligands are also crucial in determining enantiomeric discrimination and opens up a new avenue for designing chiral materials.

Lethal and sublethal effects of spinosad on dengue vector mosquito, Aedes albopictus and bancroftian filariasis vector mosquito, Culex pipiens pallens.

BACKGROUND OBJECTIVES: Aedes albopictu and Culex pipiens pallens are important vectors of many viruses and have had resistance to chemical pesticide. Spinosad is a selective biological insecticide to control urban mosquito. The aim of this study was to reveal the sublethal effects of spinosad on mosquito and provide reference basis for integrated mosquito management. METHODS: The toxicity of spinosad against Ae. albopictus and Cx. pipiens pallens were determined under laboratory conditions by exposing early third-instar larvae to different concentrations. RESULTS: The LC50 values of spinosad to Ae. albopictus and Cx. Pipiens pallens larvaes were 4.44×10-3 mg∙L-1 and 1.93×10-3 mg∙L-1 respectively after 72 h exposure. Spinosad at sublethal concentrations has many negative effects on Ae. albopictus and Cx. Pipiens pallens larval, pupae, adult and offspring eggs, including significantly reduced their larvae pupation rate by 51.37% and 58.47%, significantly prolonged pupae length by 21.43% and 16.18%, reduced female wing-spans by 20.19% and 14.89%, reduced male wing-spans by 3.84% and 7.54%, reduced female weight by 29.04% and 31.52%, reduced male weight by 7.47% and 9.07%, reduced female and male ratio by 51.98% and 45.21%, reduced individual egg-laying amount by 15.73% and 35.51%, in addition, offspring egg hatchability were dramatically decreased by 25.71% and 34.04%, egg periods were significantly prolonged by 14.42% and 62.82% respectively. No significant effect on larval period, pupae emergence rate, female bite rates were observed. INTERPRETATION CONCLUSION: These results suggest that spinosad might affect pest population dynamics significantly and is fairly expected to be a candidate biological pesticide for mosquito control.

Multicomponent Interface and Electronic Structure Engineering in Ir-Doped CoMO4-Co(OH)2 (M = W and Mo) Enable Promoted Oxygen Evolution Reaction.

The core principles of multicomponent interface and electronic structure engineering are essential in designing high-performance catalysts for the oxygen evolution reaction (OER). However, combining these aspects within a catalyst is a significant challenge. In this investigation, a novel approach involving the development of hybrid Ir-doped CoMO4-Co(OH)2 (M = W and Mo) hollow nanoboxes was introduced, enabling remarkably efficient water oxidation electrocatalysis. Constructed from ultrathin nanosheet-assembled hollow nanoboxes, these structures boast a wealth of active centers for intermediate species, which in turn enhance both charge transfer and mass transport capabilities. Moreover, the compelling electronic and synergistic effects arising from the interaction between CoMO4 and Co(OH)2 significantly bolster OER electrocatalysis by facilitating efficient electron transfer. The introduction of Ir atoms serves to strategically adjust the electronic structure, fine-tune its electronic state, and operate as active centers to enhance OER electrocatalysis, thus diminishing the overpotential. This configuration results in Ir-CoWO4-Co(OH)2 and Ir-CoMoO4-Co(OH)2 exhibiting impressively low overpotentials of 252 and 261 mV, respectively, to 10 mA cm-2. Utilized in conjunction with the Pt/C catalyst in a two-electrode system for overall water splitting, a mere 1.53 V cell potential is needed to achieve the desired 10 mA cm-2 current density.

Methyl Red degradation by a subseafloor fungus Schizophyllum commune 15R-5-F01: efficiency, pathway, and product toxicity.

Synthetic dyes pose a significant environmental threat due to their complex structures and resistance to microbial degradation. S. commune 15R-5-F01 exhibited over 96% degradation efficiency of Methyl Red in a medium with 100 mg L-1 Methyl Red within 3 h. The fungus demonstrated adaptability to various environmental conditions, including different pH levels, temperatures, oxygen concentrations, salinity, and heavy metals. S. commune 15R-5-F01 is capable of achieving repeated cycles of Methyl Red reduction with sustained degradation duration minimum of 6 cycles. It showed a maximum Methyl Red biodegradation capacity of at least 558 mg g-1 dry mycelia and a bioadsorption capacity of 57 mg g-1. Gas chromatography-mass spectrometry analysis confirmed the azo reduction of Methyl Red into N,N-dimethyl-p-phenylenediamine and 2-aminobenzoic acid. Enzymatic activity assays indicated the involvement of lignin peroxidases, laccases, and manganese peroxidase in the biodegradation process. Phytotoxicity tests on Triticum eastivum, Oryza sativa, and Vigna umbellata seeds revealed reduced toxicity of the degradation products compared to Methyl Red. This study identifies S. commune 15R-5-F01 as a viable candidate for the sustainable degradation of synthetic dyes in industrial wastewater.

Homogeneous Deposition of Zinc on N-Doped Carbon Fibers Interconnected with Sn Nanoparticles for Advanced Aqueous Zinc Batteries.

Currently, inhomogeneous distribution of Zn2+ on the surface of the Zn anode is still the essential reason for dendrite formation and unsatisfactory stability of zinc ion batteries. Given the merits of strong interaction between Sn and Zn, as well as a low nucleation barrier during Zn deposition, the combination of metallic Sn with carbon material is expected to improve the deposition of zinc ions and inhibit the growth of zinc dendrites by guiding the homogeneous plating/stripping of zinc on the electrode surface. In this article, zincophilic Sn nanoparticles with low nucleation barriers and strong interaction with Zn2+ were embedded into 3D N-doped carbon nanofibers using a simple electrostatic spinning technique. Accordingly, when serving as an artificial coating layer for the zinc metal anode, an ultrastable Sn@NCNFs@Zn||Sn@NCNFs@Zn symmetric cell can be achieved for over 3500 h with a low nucleation overpotential of 29.1 mV. Significantly, the full cell device assembled with the as-prepared anode and MnO2 cathode exhibits desirable electrochemical behaviors. Moreover, this simple method could be extended to other metal-carbon composites, and to ensure ease in scaling up as required. Such significant approach can provide an effective strategy for the design of high-performance zinc anodes.

Psychopathology of cognitive disengagement syndrome (CDS): a network analysis based on CBCL scales in 72,106 Chinese school students.

Cognitive Disengagement Syndrome (CDS) is a cluster of behavioral problems that severely affect an individual's functioning. Currently, there is no consensus on the main clinical features of CDS, and further exploration in large samples is needed. Using a cluster-stratified random sampling method, 72,106 children and adolescents were recruited from five provinces in mainland China for this study. Using both the traditional two-factor scoring method and the CBCL DSM-oriented scales, we assessed individual behavioral problems from psychopathological and DSM-oriented perspectives. Network analysis was employed to explore the relationship between CDS and behavioral problems. The various networks were compared by gender and age subgroups. Among 72,106 participants (mean age, 11.49 years; minimum age, 5 years; maximum age, 16 years), there were 36,449 males (50.5%) and 35,657 females (49.5%). From a psychopathological perspective, the motor symptoms node was associated with the sad node and the withdrawn node, while the cognitive symptoms node was linked to the nervous node and the self-conscious node. In terms of gender, males had stronger associations of the motor symptoms node with the sad node and the withdrawn node than females (P = 0.043), and weaker associations of the cognitive symptoms node with the nervous node than females (P = 0.027). In terms of growth stage, the adolescent group had stronger associations of the cognitive symptoms node with the nervous node and the self-conscious node than the child group (P = 0.016, 0.001). From DSM perspective, motor symptoms node were associated with sad node, and cognitive symptoms node were related to can't concentrate node, nervous node, and worthless node. With increasing age, there was an upward trend in the strength of the cognitive and motor symptoms node. CDS is closely linked to psychological and behavioral issues, especially internalizing problems, with differences observed by gender and growth stage. The connection between CDS and the affective, anxiety, and ADH symptoms is particularly pronounced.

Skeletal Editing of Aromatic N-Heterocycles via Hydroborative Cleavage of C-N Bonds - Scope, Mechanism, and Property.

Skeletal editing of the core structure of heterocycles offers new opportunities for chemical construction and is a promising yet challenging research topic that has recently gained increasing interest. However, several limitations of the reported systems remain to be addressed. For example, the reagents employed are generally in high-energy, such as chlorocarbene precursors, nitrene species, and metal carbenes, which are also associated with low atomic efficiencies. Thus, the development of simple systems for the skeletal editing of heterocycles is still desired. Herein, a straightforward and facile BH3-mediated skeletal editing of readily available indoles, benzimidazoles, and several other aromatic heterocycles is reported. Structurally diverse products were readily obtained, including tetrahydrobenzo azaborinines, diazaboroles, O-anilinophenylethyl alcohols, benzene-1,2-diamines, and more. Density functional theory (DFT) calculations and natural bond orbital (NBO) analysis revealed a BH3-induced C-N bond cleavage reaction pathway. An exciting and counterintuitive indole hydroboration phenomenon of -BH2 shift from C3-position to C2-position was disclosed. Moreover, the photophysical properties of the synthesized diazaboroles were studied, and an interestingly and pronounced aggregation-induced emission (AIE) behavior was disclosed.

Forensic stability evaluation of selected miRNA and circRNA markers in human bloodstained samples exposed to different environmental conditions.

Recently, RNA markers have been used to identify tissue origins of different kinds of body fluids. Herein, circRNA and miRNA markers were carried out to examine the presence or absence of peripheral blood (PB) in bloodstained samples exposed to different external environmental conditions, which mimicked PB samples left at the crime scenes. PB samples were placed on sterile swabs and then exposed to different high temperatures (37°C, 55°C and 95°C) and ultraviolet light irradiation for 0 d, 0.5 d, 1 d, 3 d, and 7 d, ultra-low and low temperatures (-80°C, -20°C, and 4°C) for 30 d, 180 d and 365 d and different kinds of disinfectants. Total RNA was extracted from bloodstained samples under the above different conditions, and the expressions of target RNAs (including miR16-5p, miR451a, circ0000095, and two reference genes RNU6b and 18 S rRNA) were detected by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) method. Results showed that these selected RNA markers could be successfully measured at all observation points with their unique degradation rates, which exhibited relative stability in degraded bloodstained samples exposed to different environmental conditions. This study provides insights into the applications of these studied miRNA and circRNA markers in forensic science.

Otilonium bromide ameliorates pulmonary fibrosis in mice through activating phosphatase PPM1A.

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease characterized by unremitting pulmonary myofibroblasts activation, extracellular matrix (ECM) deposition and inflammatory recruitment. PF has no curable medication yet. In this study we investigated the molecular pathogenesis and potential therapeutic targets of PF and discovered drug lead compounds for PF therapy. A murine PF model was established in mice by intratracheal instillation of bleomycin (BLM, 5 mg/kg). We showed that the protein level of pulmonary protein phosphatase magnesium-dependent 1A (PPM1A, also known as PP2Cα) was significantly downregulated in PF patients and BLM-induced PF mice. We demonstrated that TRIM47 promoted ubiquitination and decreased PPM1A protein in PF progression. By screening the lab in-house compound library, we discovered otilonium bromide (OB, clinically used for treating irritable bowel syndrome) as a PPM1A enzymatic activator with an EC50 value of 4.23 µM. Treatment with OB (2.5, 5 mg·kg-1·d-1, i.p., for 20 days) significantly ameliorated PF-like pathology in mice. We constructed PF mice with PPM1A-specific knockdown in the lung tissues, and determined that by targeting PPM1A, OB treatment suppressed ECM deposition through TGF-ß/SMAD3 pathway in fibroblasts, repressed inflammatory responses through NF-κB/NLRP3 pathway in alveolar epithelial cells, and blunted the crosstalk between inflammation in alveolar epithelial cells and ECM deposition in fibroblasts. Together, our results demonstrate that pulmonary PPM1A activation is a promising therapeutic strategy for PF and highlighted the potential of OB in the treatment of the disease.

Novel extracellular lipase gene Lip1728 influences nutrient-dependent performance bacterial quorum sensing of Burkholderia pyrrocinia WZ10-3.

Quorum sensing (QS) is a cellular communication mechanism in which bacteria secrete and recognize signaling molecules to regulate group behavior. Lipases provide energy for bacterial cell growth but it is unknown whether they influence nutrient-dependent QS by hydrolyzing substrate. A high-yield lipase-producing strain, Burkholderia pyrrocinia WZ10-3, was previously identified in our laboratory, but the composition of its crude enzymes was not elucidated. Here, we identified a key extracellular lipase, Lip1728, in WZ10-3, which accounts for 99 % of the extracellular lipase activity. Lip1728 prefers to hydrolyze triglycerides at sn-1,3 positions, with pNP-C16 being its optimal substrate. Lip1728 exhibited activity at pH 5.0-10.0 and regardless of the presence of metal ions. It had strong resistance to sodium dodecyl sulfate and short-chain alcohols and was activated by phenylmethanesulfonylfluoride (PMSF). Lip1728 knockout significantly affected lipid metabolism and biofilm formation in the presence of olive oil. Finally, oleic acid, a hydrolysate of Lip1728, influenced the production of the signal molecule N-acyl homoserine lactone (AHL) and biofilm formation by downregulating the AHL synthetase gene pyrI. In conclusion, Lip1728, as a key extracellular lipase in B. pyrrocinia WZ10-3, exhibits superior properties that make it suitable for biodiesel production and plays a crucial role in QS.