Polystyrene nano-plastics impede skeletal muscle development and induce lipid accumulation via the PPARγ/LXRß pathway in vivo and in vitro in mice.

Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRß pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 µg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRß as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRß, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRß pathway thereby influencing skeletal muscle development.

A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch.

Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety. In addition, chronic itch is accompanied with enhanced activity and synaptic plasticity of excitatory projections from the thalamic nucleus reuniens (Re) onto LS GABAergic neurons. Selective chemogenetic inhibition of the Re → LS circuit notably alleviated chronic itch-induced anxiety, with no impact on anxiety induced by restraint stress. Last, GABAergic neurons in lateral hypothalamus (LH) receive monosynaptic inhibition from LS GABAergic neurons to mediate chronic itch-induced anxiety. These findings underscore the potential significance of the Re → LS → LH pathway in regulating anxiety-like comorbid symptoms associated with chronic itch.

Constrained motion of self-propelling eccentric disks linked by a spring.

It has been supposed that the interplay of elasticity and activity plays a key role in triggering the non-equilibrium behaviors in biological systems. However, the experimental model system is missing to investigate the spatiotemporally dynamical phenomena. Here, a model system of an active chain, where active eccentric-disks are linked by a spring, is designed to study the interplay of activity, elasticity, and friction. Individual active chain exhibits longitudinal and transverse motions; however, it starts to self-rotate when pinning one end and self-beat when clamping one end. In addition, our eccentric-disk model can qualitatively reproduce such behaviors and explain the unusual self-rotation of the first disk around its geometric center. Furthermore, the structure and dynamics of long chains were studied via simulations without steric interactions. It was found that a hairpin conformation emerges in free motion, while in the constrained motions, the rotational and beating frequencies scale with the flexure number (the ratio of self-propelling force to bending rigidity), χ, as ∼(χ)4/3. Scaling analysis suggests that it results from the balance between activity and energy dissipation. Our findings show that topological constraints play a vital role in non-equilibrium synergy behaviors.

Progress in the application of artificial intelligence in skin wound assessment and prediction of healing time.

Since the 1970s, artificial intelligence (AI) has played an increasingly pivotal role in the medical field, enhancing the efficiency of disease diagnosis and treatment. Amidst an aging population and the proliferation of chronic disease, the prevalence of complex surgeries for high-risk multimorbid patients and hard-to-heal wounds has escalated. Healthcare professionals face the challenge of delivering safe and effective care to all patients concurrently. Inadequate management of skin wounds exacerbates the risk of infection and complications, which can obstruct the healing process and diminish patients' quality of life. AI shows substantial promise in revolutionizing wound care and management, thus enhancing the treatment of hospitalized patients and enabling healthcare workers to allocate their time more effectively. This review details the advancements in applying AI for skin wound assessment and the prediction of healing timelines. It emphasizes the use of diverse algorithms to automate and streamline the measurement, classification, and identification of chronic wound healing stages, and to predict wound healing times. Moreover, the review addresses existing limitations and explores future directions.

PRMT1 and TDRD3 promote stress granule assembly by rebuilding the protein-RNA interaction network.

Stress granules (SGs) are membrane-less organelles (MLOs) or cytosolic compartments formed upon exposure to environmental cell stress-inducing stimuli. SGs are based on ribonucleoprotein complexes from a set of cytoplasmic proteins and mRNAs, blocked in translation due to stress cell-induced polysome disassembly. Post-translational modifications (PTMs) such as methylation, are involved in SG assembly, with the methylation writer PRMT1 and its reader TDRD3 colocalizing to SGs. However, the role of this writer-reader system in SG assembly remains unclear. Here, we found that PRMT1 methylates SG constituent RNA-binding proteins (RBPs) on their RGG motifs. Besides, we report that TDRD3, as a reader of asymmetric dimethylarginines, enhances RNA binding to recruit additional RNAs and RBPs, lowering the percolation threshold and promoting SG assembly. Our study enriches our understanding of the molecular mechanism of SG formation by elucidating the functions of PRMT1 and TDRD3. We anticipate that our study will provide a new perspective for comprehensively understanding the functions of PTMs in liquid-liquid phase separation driven condensate assembly.

Size Reduction to Enhance Crystal-to-Liquid Phase Transition Induced by E-to-Z Photoisomerization Based on Molecular Crystals of Phenylbutadiene Ester.

Harnessing the photoinduced phase transitions in organic crystals, especially the changes in shape and structure across various dimensions, offers a fascinating avenue for exact spatiotemporal control, which is crucial for developing future smart devices. In our study, we report a new photoactive molecular crystal made from (E)-2-(3-phenyl-allylidene)malonate ((E)-PADM). When exposed to ultraviolet (UV) light at 365 nm, this compound experiences an E-to-Z photoisomerization in liquid solution and a crystal-to-liquid phase transition in solid crystals. Remarkably, nanoscopic crystalline rods boost their melting rate and degree compared to bulk crystals, indicating that miniaturization enhances the photoinduced melting effect. Our results demonstrate a simple approach to rapidly drive molecular crystals into liquids via photochemical reactions and phase transitions.

Pyroptosis and the fight against lung cancer.

Pyroptosis, a newly characterized type of inflammatory programmed cell death (PCD), is usually triggered by multiple inflammasomes which can recognize different danger or damage-associated molecular patterns (DAMPs), leading to the activation of caspase-1 and the cleavage of gasdermin D (GSDMD). Gasdermin family pore-forming proteins are the executers of pyroptosis and are normally maintained in an inactive state through auto-inhibition. Upon caspases mediated cleavage of gasdermins, the pro-pyroptotic N-terminal fragment is released from the auto-inhibition of C-terminal fragment and oligomerizes, forming pores in the plasma membrane. This results in the secretion of interleukin (IL)-1ß, IL-18, and high-mobility group box 1 (HMGB1), generating osmotic swelling and lysis. Current therapeutic approaches including chemotherapy, radiotherapy, molecularly targeted therapy and immunotherapy for lung cancer treatment efficiently force the cancer cells to undergo pyroptosis, which then generates local and systemic antitumor immunity. Thus, pyroptosis is recognized as a new therapeutic regimen for the treatment of lung cancer. In this review, we briefly describe the signaling pathways involved in pyroptosis, and endeavor to discuss the antitumor effects of pyroptosis and its potential application in lung cancer therapy, focusing on the contribution of pyroptosis to microenvironmental reprogramming and evocation of antitumor immune response.

Transcriptome analysis of the diseased intervertebral disc tissue in patients with spinal tuberculosis.

OBJECTIVE: To investigate the differential expression genes (DEGs) in spinal tuberculosis using transcriptomics, with the aim of identifying novel therapeutic targets and prognostic indicators for the clinical management of spinal tuberculosis. METHODS: Patients who visited the Department of Orthopedics at the Second Hospital, Lanzhou University from January 2021 to May 2023 were enrolled. Based on the inclusion and exclusion criteria, there were 5 patients in the test group and 5 patients in the control group. Total RNA was extracted and paired-end sequencing was conducted on the sequencing platform. After processing the sequencing data with clean reads and annotating the reference genome, FPKM normalization and differential expression analysis were performed. The DEGs and long non-coding RNAs (LncRNAs) were analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. The cis-regulation of differentially expressed mRNAs (DE mRNAs) by LncRNAs was predicted and analyzed to establish a co-expression network. RESULTS: This study identified 2366 DEGs, with 974 genes significantly upregulated and 1392 genes significantly downregulated. The upregulated genes are associated with cytokine-cytokine receptor interactions, tuberculosis, and TNF-α signaling pathways, primarily enriched in biological processes such as immunity and inflammation. The downregulated genes are related to muscle development, contraction, fungal defense response, and collagen metabolism processes. Analysis of LncRNAs from bone tuberculosis RNA-seq data detected a total of 3652 LncRNAs, with 356 significantly upregulated and 184 significantly downregulated. Further analysis identified 311 significantly different LncRNAs that could cis-regulate 777 target genes, enriched in pathways such as muscle contraction, inflammatory response, and immune response, closely related to bone tuberculosis. There are 51 genes enriched in the immune response pathway regulated by cis-acting LncRNAs. LncRNAs that regulate immune response-related genes, such as upregulated RP11-451G4.2, RP11-701P16.5, AC079767.4, AC017002.1, LINC01094, CTA-384D8.35, and AC092484.1, as well as downregulated RP11-2C24.7, may serve as potential prognostic and therapeutic targets. CONCLUSION: The DE mRNAs and LncRNAs in spinal tuberculosis are both associated with immune regulatory pathways. These pathways promote or inhibit the tuberculosis infection and development at the mechanistic level and play an important role in the process of tuberculosis transferring to bone tissue.

Meta-analysis of robotic-assisted NOSE versus traditional TWSR in colorectal cancer surgery: postoperative outcomes and efficacy.

BACKGROUND: This meta-analysis aimed to assess the safety and efficacy of robotic-assisted natural orifice specimen extraction surgery (NOSE) compared to traditional robotic transabdominal wall specimen retrieval surgery (TWSR) for colorectal cancer. METHODS: A systematic search was conducted in three electronic databases (PubMed, Web of Science and Embase) from inception to August 2023. Primary outcomes included postoperative complications, the number of lymph nodes harvested, overall survival and disease-free survival. Secondary outcomes included the postoperative visual analog scale (VAS) score, the additional use of analgesics, the restoration of gastrointestinal function, blood loss, the mean operation time, and length of postoperative hospital stay. RESULTS: In this meta-analysis, a total of 717 patients from 6 observational studies met the inclusion criteria. Compared with the TWSR group, the NOSE group had greater benefits in terms of overall postoperative complications [odds ratios (OR) 0.55; 95% confidence intervals (CI) = 0.34 to 0.89; P = 0.01, I2 = 0%)], the number of lymph nodes harvested [weighted mean differences (WMD) = 1.18; 95% CI = 0.15 to 2.21; P = 0.02, I2 = 0%)], the rate of wound infection (OR 0.17; 95% CI = 0.04 to 0.80; P = 0.02, I2 = 0%), the passed flatus time (WMD = - 0.35 days; 95% CI = - 0.60 to - 0.10; P = 0.007, I2 = 73%), the additional use of analgesics (OR 0.25; 95% CI = 0.15 to 0.40; P < 0.001, I2 = 0%), the diet recovery time (WMD = - 0.56; 95% CI = - 1.00 to - 0.11; P = 0.01, I2 = 78%) and the postoperative VAS score (WMD = - 1.23; 95% CI = - 1.63 to - 0.83; P < 0.001, I2 = 65%). There were no significant differences in the blood loss (WMD = - 5.78 ml; 95% CI = - 17.57 to 6.00; P = 0.34, I2 = 90%), mean operation time (WMD = 14.10 min; 95% CI = - 3.76 to 31.96; P = 0.12) (I2 = 93%), length of postoperative hospital stay (WMD = - 0.47 day; 95% CI = - 0.98 to 0.03; P = 0.07, I2 = 51%), incidences of postoperative ileus (OR 1.0; 95% CI = 0.22 to 4.46; P = 1.00, I2 = 0%), anastomotic leakage (OR 0.73; 95% CI = 0.33 to 1.60; P = 0.43, I2 = 0%), and intra-abdominal abscess (OR 1.59; 95% CI = 0.47 to 5.40; P = 0.46, I2 = 0%), or 3-year overall survival [hazard ratio (HR) = 1.07, 95% CI = 0.60 to 1.94; P = 0.81)] or disease-free survival (HR = 0.94, 95% CI = 0.54 to 1.63; P = 0.82, I2 = 0%). CONCLUSION: This meta-analysis showed that the NOSE group had better postoperative outcomes than did the TWSR group and that NOSE was a safe and viable alternative to TWSR. More large-sample reviews and further randomized trials are warranted.

The Key Phytochemical Cue Camphor Is a Promising Lure for Traps Monitoring the New Monophagous Camphor Tree Borer Pagiophloeus tsushimanus (Coleoptera: Curculionidae).

The landscape plant, Cinnamomum camphora, is a broad-spectrum insect-repelling tree species, mainly due to a diversity of terpenoids, such as camphor. Despite its formidable chemical defenses, C. camphora is easily attacked and invaded by a monophagous weevil pest, Pagiophloeus tsushimanus. Deciphering the key olfactory signal components regulating host preference could facilitate monitoring and control strategies for this pest. Herein, two host volatiles, camphor and ocimene, induced GC-EAD/EAG reactions in both male and female adult antennae. Correspondingly, Y-tube olfactometer assays showed that the two compounds were attractive to both male and female adults. In field assays, a self-made trap device baited with 5 mg dose d(+)-camphor captured significantly more P. tsushimanus adults than isopropanol solvent controls without sexual bias. The trunk gluing trap device baited with bait can capture adults, but the number was significantly less than that of the self-made trap device and adults often fell after struggling. The cross baffle trap device never trapped adults. Neither ocimene nor isopropanol solvent control captured adults. When used in combination, ocimene did not enhance the attraction of d(+)-camphor to both female and male adults. These results indicate that d(+)-camphor is a key active compound of P. tsushimanus adults for host location. The combination of the host-volatile lure based on d(+)-camphor and the self-made trapping device is promising to monitor and provide an eco-friendly control strategy for this novel pest P. tsushimanus in C. camphora plantations.

The Coptidis Rhizoma and Bovis Calculus herb pair attenuates NASH and inhibits the NLRP3 inflammasome activation.

The Coptidis Rhizoma and Bovis Calculus herb pair possesses clearing heat and detoxifying effects. The aim of this study was to reveal the effects and mechanisms of the herb pair in the treatment of NASH by network pharmacology and experimental verification. A network pharmacology-based approach was employed to predict the putative mechanism of the herb pair against NASH. The high-fat diet (HFD) and methionine/choline deficient (MCD) diet induced NASH models were used to evaluate efficacy and mechanism of the herb pair. Network pharmacological analysis showed that the herb pair modulated NOD-like receptor pathway. In the HFD mice, herb pair reduced body weight, blood sugar, serum ALT, AST, TBA, TC, TG and LDL-C contents, also improved the general morphology and pathological manifestations. Hepatic transcriptomics study showed that herb pair attenuated NASH by regulating NOD-like receptor signaling pathway. Western blotting showed that herb pair reduced the protein expression levels of NLRP3, cleaved Caspase-1 and cleaved IL-1ß. In the MCD mice, herb pair also reduced serum ALT, ALT and TBA levels, improved liver pathological manifestations, inhibited the protein expression levels of NLRP3, cleaved Caspase-1 and cleaved IL-1ß. Our findings proved that the Coptidis Rhizoma and Bovis Calculus herb pair attenuates NASH through suppression of NLRP3 inflammasome activation. This will demonstrate effective pharmacological evidence for the clinical application of herb pair.

Blood Pressure Fluctuation During 72 Hours After Endovascular Therapy and Prognosis in Acute Ischemic Stroke Patients.

PURPOSE: Our study aimed to investigate the relationship between fluctuations in different blood pressure (BP) components within 72 hours following endovascular therapy (EVT) and the prognosis of acute ischemic stroke (AIS) patients. METHODS: This prospective multicenter study included 283 AIS patients who underwent EVT and had available BP data. The primary outcome was the ordinal modified Rankin Scale (mRS) score evaluated at 90 days. The secondary outcome was a combination of death and major disability, defined as an mRS score of 3 to 6 within 3 months. RESULTS: After adjusting for imbalanced variables, the highest tertile of systolic blood pressure (SBP) fluctuation had an odds ratio (OR) of 1.747 (95% confidence interval [CI]=1.031-2.961; p for trend=0.035) for the primary outcome and 1.889 (95% CI=1.015-3.516; p for trend=0.039) for the secondary outcome, respectively. Fluctuations in diastolic blood pressure (DBP) (OR=1.914, 95% CI=1.134-3.230, p for trend=0.015) and mean arterial pressure (MAP) (OR=1.759, 95% CI=1.026-3.015, p for trend=0.039) were only associated with the primary outcome. The multivariate-adjusted restricted cubic spline analyses supported these findings. Furthermore, the fluctuations in both SBP and MAP exhibited the significant discriminatory capability in predicting the prognosis, comparable to their mean values. CONCLUSION: Our study revealed that larger fluctuations in SBP, DBP, and MAP within 72 hours after EVT were associated with a higher risk of poor clinical outcomes within 3 months in AIS patients. Controlling BP fluctuations may be valuable for improving the prognosis in patients undergoing EVT. CLINICAL IMPACT: How will this change clinical practice?It provides physicians a new approach to directly monitor BP fluctuations over an extended observation period in AIS patients after EVT in routine clinical practice.What does it mean for the clinicians?These results underscore the importance of giving equal attention to controlling long-term BP fluctuations, in addition to managing mean BP, as a means to improve the prognosis of AIS patients after EVT.What is the innovation behind the study?This study systematically evaluated the association between fluctuations in different blood pressure components and clinical outcomes in AIS patients over an extended period following EVT.

Glutamate acts on acid-sensing ion channels to worsen ischaemic brain injury.

Glutamate is traditionally viewed as the first messenger to activate NMDAR (N-methyl-D-aspartate receptor)-dependent cell death pathways in stroke1,2, but unsuccessful clinical trials with NMDAR antagonists implicate the engagement of other mechanisms3-7. Here we show that glutamate and its structural analogues, including NMDAR antagonist L-AP5 (also known as APV), robustly potentiate currents mediated by acid-sensing ion channels (ASICs) associated with acidosis-induced neurotoxicity in stroke4. Glutamate increases the affinity of ASICs for protons and their open probability, aggravating ischaemic neurotoxicity in both in vitro and in vivo models. Site-directed mutagenesis, structure-based modelling and functional assays reveal a bona fide glutamate-binding cavity in the extracellular domain of ASIC1a. Computational drug screening identified a small molecule, LK-2, that binds to this cavity and abolishes glutamate-dependent potentiation of ASIC currents but spares NMDARs. LK-2 reduces the infarct volume and improves sensorimotor recovery in a mouse model of ischaemic stroke, reminiscent of that seen in mice with Asic1a knockout or knockout of other cation channels4-7. We conclude that glutamate functions as a positive allosteric modulator for ASICs to exacerbate neurotoxicity, and preferential targeting of the glutamate-binding site on ASICs over that on NMDARs may be strategized for developing stroke therapeutics lacking the psychotic side effects of NMDAR antagonists.

C-reactive protein: structure, function, regulation, and role in clinical diseases.

C-reactive protein (CRP) is a plasma protein that is evolutionarily conserved, found in both vertebrates and many invertebrates. It is a member of the pentraxin superfamily, characterized by its pentameric structure and calcium-dependent binding to ligands like phosphocholine (PC). In humans and various other species, the plasma concentration of this protein is markedly elevated during inflammatory conditions, establishing it as a prototypical acute phase protein that plays a role in innate immune responses. This feature can also be used clinically to evaluate the severity of inflammation in the organism. Human CRP (huCRP) can exhibit contrasting biological functions due to conformational transitions, while CRP in various species retains conserved protective functions in vivo. The focus of this review will be on the structural traits of CRP, the regulation of its expression, activate complement, and its function in related diseases in vivo.

Recycled Cathodes in Rechargeable Aqueous Batteries as Ready-Made Electrodes for Oxygen Evolution Catalysis.

The development of a low-cost and efficient oxygen evolution reaction (OER) electrode is of critical importance for water electrolysis technologies. The general approach to achieving a high-efficiency OER electrode is to regulate catalytic material structures by synthetic control. Here we reported an orthogonal approach to obtaining the OER electrode without intentional design and synthesis, namely, recycling MnO2 cathodes from failed rechargeable aqueous batteries and investigating them as ready-made catalytic electrodes. The recycled MnO2 cathode showed very little Zn2+ storage capacity but surprisingly high OER activity with a low overpotential of 307 mV at 10 mA cm-2 and a small Tafel slope of 77.9 mV dec-1, comparable to the state-of-the-art RuO2 catalyst (310 mV, 86.9 mV dec-1). In situ electrochemical and theoretical studies jointly revealed that the accelerated OER kinetics of the recycled MnO2 electrode was attributed to the enlarged active surface area of MnO2 and optimized electronic structure of Mn sites. This work suggests failed battery cathodes as successful catalysis electrodes for sustainable energy development.

Ectopic Activation of Fgf8 in Dental Mesenchyme Causes Incisor Agenesis and Molar Microdontia.

Putatively, tooth agenesis was attributed to the initiation failure of tooth germs, though little is known about the histological and molecular alterations. To address if constitutively active FGF signaling is associated with tooth agenesis, we activated Fgf8 in dental mesenchyme with Osr-cre knock-in allele in mice (Osr2-creKI; Rosa26R-Fgf8) and found incisor agenesis and molar microdontia. The cell survival assay showed tremendous apoptosis in both the Osr2-creKI; Rosa26R-Fgf8 incisor epithelium and mesenchyme, which initiated incisor regression from cap stage. In situ hybridization displayed vanished Shh transcription, and immunostaining exhibited reduced Runx2 expression and enlarged mesenchymal Lef1 domain in Osr2-creKI; Rosa26R-Fgf8 incisors, both of which were suggested to enhance apoptosis. In contrast, Osr2-creKI; Rosa26R-Fgf8 molar germs displayed mildly suppressed Shh transcription, and the increased expression of Ectodin, Runx2 and Lef1. Although mildly smaller than WT controls prenatally, the Osr2-creKI; Rosa26R-Fgf8 molar germs produced a miniature tooth with impaired mineralization after a 6-week sub-renal culture. Intriguingly, the implanted Osr2-creKI; Rosa26R-Fgf8 molar germs exhibited delayed odontoblast differentiation and accelerated ameloblast maturation. Collectively, the ectopically activated Fgf8 in dental mesenchyme caused incisor agenesis by triggering incisor regression and postnatal molar microdontia. Our findings reported tooth agenesis resulting from the regression from the early bell stage and implicated a correlation between tooth agenesis and microdontia.

Mass spectrometry-intensive top-down proteomics: an update on technology advancements and biomedical applications.

Proteoforms are all forms of protein molecules from the same gene because of variations at the DNA, RNA, and protein levels, e.g., alternative splicing and post-translational modifications (PTMs). Delineation of proteins in a proteoform-specific manner is crucial for understanding their biological functions. Mass spectrometry (MS)-intensive top-down proteomics (TDP) is promising for comprehensively characterizing intact proteoforms in complex biological systems. It has achieved substantial progress in technological development, including sample preparation, proteoform separations, MS instrumentation, and bioinformatics tools. In a single TDP study, thousands of proteoforms can be identified and quantified from a cell lysate. It has also been applied to various biomedical research to better our understanding of protein function in regulating cellular processes and to discover novel proteoform biomarkers of diseases for early diagnosis and therapeutic development. This review covers the most recent technological development and biomedical applications of MS-intensive TDP.

Eating Styles Profiles and Correlates in Chinese Postpartum Women: A Latent Profile Analysis.

Postpartum women present a high risk of disordered eating behaviors, but the heterogeneity between groups was not identified. This cross-sectional study aimed to identify eating styles profiles in postpartum women and explore the correlates based on demographic characteristics and psychosocial factors. Questionnaires were administered to 507 Chinese postpartum women. Latent profile analysis (LPA) was conducted to identify eating styles profiles. Multinomial logistic regression was used to investigate the correlates of these profiles among postpartum women. The LPA identified three eating styles profiles: postpartum women with low emotional, external, and restrained eating (Profile 1, 6.9%); postpartum women with medium emotional, external, and restrained eating (Profile 2, 66.1%); and postpartum women with high emotional, external, and restrained eating (Profile 3, 27.0%). Compared to Profile 1, higher postpartum depression (PPD) and body mass index (BMI) were more likely to be associated with Profile 2 and Profile 3, whereas higher postpartum weight retention (PPWR) was more likely to be associated with Profile 1. Compared to Profile 2, higher PPD and BMI were more likely associated with Profile 3. Disordered eating behaviors in postpartum women with three eating styles were associated with BMI, PPD, and PPWR. This study can guide healthcare professionals in developing targeted interventions to improve maternal and child health globally.

A multi-iron enzyme installs copper-binding oxazolone/thioamide pairs on a nontypeable Haemophilus influenzae virulence factor.

The multinuclear nonheme iron-dependent oxidases (MNIOs) are a rapidly growing family of enzymes involved in the biosynthesis of ribosomally synthesized, posttranslationally modified peptide natural products (RiPPs). Recently, a secreted virulence factor from nontypeable Haemophilus influenzae (NTHi) was found to be expressed from an operon, which we designate the hvf operon, that also encodes an MNIO. Here, we show by Mössbauer spectroscopy that the MNIO HvfB contains a triiron cofactor. We demonstrate that HvfB works together with HvfC [a RiPP recognition element (RRE)-containing partner protein] to perform six posttranslational modifications of cysteine residues on the virulence factor precursor peptide HvfA. Structural characterization by tandem mass spectrometry and NMR shows that these six cysteine residues are converted to oxazolone and thioamide pairs, similar to those found in the RiPP methanobactin. Like methanobactin, the mature virulence factor, which we name oxazolin, uses these modified residues to coordinate Cu(I) ions. Considering the necessity of oxazolin for host cell invasion by NTHi, these findings point to a key role for copper during NTHi infection. Furthermore, oxazolin and its biosynthetic pathway represent a potential therapeutic target for NTHi.

A pilot study for deciphering post-translational modifications and proteoforms of tau protein by capillary electrophoresis-mass spectrometry.

Abnormal accumulation of tau proteins is one pathological hallmark of Alzheimer□s disease (AD). Many tau protein post-translational modifications (PTMs) are associated with the development of AD, such as phosphorylation, acetylation, and methylation. Therefore, a complete picture of PTM landscape of tau is critical for understanding the molecular mechanisms of AD progression. Here, we offered a pilot study of combining two complementary analytical techniques, capillary zone electrophoresis (CZE)-tandem mass spectrometry (MS/MS) and reversed-phase liquid chromatography (RPLC)-MS/MS, for bottom-up proteomics of recombinant human tau-0N3R. We identified 53 phosphorylation sites of tau-0N3R in total, which is about 30% higher than that from RPLC-MS/MS alone. CZE-MS/MS provided more PTM sites (i.e., phosphorylation) and modified peptides of tau-0N3R than RPLC-MS/MS, and its predicted electrophoretic mobility helped improve the confidence of the identified modified peptides. We developed a highly efficient capillary isoelectric focusing (cIEF)-MS technique to offer a bird's-eye view of tau-0N3R proteoforms, with 11 putative tau-0N3R proteoforms carrying up to nine phosphorylation sites and lower pI values from more phosphorylated proteoforms detected. Interestingly, under a native-like cIEF-MS condition, we observed three putative tau-0N3R dimers carrying phosphate groups. The findings demonstrate that CE-MS is a valuable analytical technique for the characterization of tau PTMs, proteoforms, and even oligomerization.