Polypropylene mesh coated with hyaluronic acid/polyvinyl alcohol composite hydrogel for preventing bowel adhesion.

Polypropylene (PP) mesh is the most widely used prosthetic material in hernia repair. However, the efficacy of implanted PP mesh is often compromised by adhesion between viscera and PP mesh. Thus, there is a recognized need for developing an anti-adhesive PP mesh. Here, a composite hydrogel coated PP mesh with the prevention of adhesion after hernia repair was designed. The composite hydrogel coating was prepared from polyvinyl alcohol (PVA) and hyaluronic acid (HA) by using the freezing-thawing (FT) method. To overcome the shortcoming of the long time of the traditional freezing-thawing method, a small molecule 3,4-dihydroxyphenylacetic acid (DHPA) was introduced to promote the formation of composite hydrogel. The as-prepared composite hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro studies illustrated that the resulting meshes showed excellent coating stability, hemocompatibility, and non-cytotoxicity. In vivo experiments using a rat abdominal wall defect model demonstrated that the composite hydrogel coated PP mesh could prevent the formation of adhesion, alleviate the inflammatory response, and reduce the deposition of collagen around the damaged tissue. These disclosed results manifested that the PP mesh coated with HA/PVA composite hydrogel might be a promising application in preventing adhesion for hernia repair.

Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia.

BACKGROUND: Sleep loss is a common public health problem that causes hyperalgesia, especially that after surgery, which reduces the quality of life seriously. METHODS: The 48-h sleep restriction (SR) mouse model was created using restriction chambers. In vivo imaging, transmission electron microscopy (TEM), immunofluorescence staining and Western blot were performed to detect the status of the blood-spinal cord barrier (BSCB). Paw withdrawal mechanical threshold (PWMT) was measured to track mouse pain behavior. The role of infiltrating regulatory T cells (Tregs) and endothelial cells (ECs) in mouse glycolysis and BSCB damage were analyzed using flow cytometry, Western blot, CCK-8 assay, colorimetric method and lactate administration. RESULTS: The 48-h SR made mice in sleep disruption status and caused an acute damage to the BSCB, resulting in hyperalgesia and neuroinflammation in the spinal cord. In SR mice, the levels of glycolysis and glycolysis enzymes of ECs in the BSCB were found significantly decreased [CON group vs. SR group: CD31+Glut1+ cells: p < 0.001], which could cause dysfunction of ECs and this was confirmed in vitro. Increased numbers of infiltrating T cells [p < 0.0001] and Treg population [p < 0.05] were detected in the mouse spinal cord after 48-h SR. In the co-cultured system of ECs and Tregs in vitro, the competition of Tregs for glucose resulted in the glycolysis disorder of ECs [Glut1: p < 0.01, ENO1: p < 0.05, LDHα: p < 0.05; complete tubular structures formed: p < 0.0001; CCK8 assay: p < 0.001 on 24h, p < 0.0001 on 48h; glycolysis level: p < 0.0001]. An administration of sodium lactate partially rescued the function of ECs and relieved SR-induced hyperalgesia. Furthermore, the mTOR signaling pathway was excessively activated in ECs after SR in vivo and those under the inhibition of glycolysis or co-cultured with Tregs in vitro. CONCLUSIONS: Affected by glycolysis disorders of ECs due to glucose competition with infiltrating Tregs through regulating the mTOR signaling pathway, hyperalgesia induced by 48-h SR is attributed to neuroinflammation and damages to the barriers, which can be relieved by lactate supplementation.

Involvement of Spinal Neuroplastin 65 in Neuropathic Pain by GABAA Receptor α2 Subunit Regulation.

BACKGROUND: Neuropathic pain (NP) is a highly challenging condition with complex pathological mechanisms, and the spinal gamma aminobutyric acid A receptor receptor plays a crucial role in its progression. Recent studies have revealed a potential interaction between neuroplastin 65 (NP65) and gamma aminobutyric acid A receptor α2 subunit (GABAAR-α2) on the cell surface. We hypothesize that NP65 is involved in the pathogenesis of NP by regulating the level of GABAAR-α2. METHODS: A chronic constrictive injury (CCI) pain model was established in male Sprague-Dawley rats to verify the change in spinal NP65 expression. Alterations in pain behavior and GABAAR-α2 protein expression were observed after intrathecal injection of NP65 overexpressing adeno-associated virus (AAV) in CCI rats. In vitro investigations on Neuroblastoma 2a cells, the effect of NP65 on GABAAR-α2 expression via the calcineurin-nuclear factor of activated T-cell 4 (CaN-NFATc4) signaling pathway was evaluated by manipulating NP65 expression. RESULTS: The expression level of NP65 protein and mRNA in the CCI group were significantly decreased (P < .05; analysis of variance [ANOVA]). After intrathecal injection of NP65, overexpression of AAV and pain behavior in CCI rats were significantly alleviated, and levels of GABAAR-α2 were upregulated. In vitro experiments verified alterations in the expression of GABAAR-α2, CaN, and phosphorylated NFATc4 on the application of NP65 with plasmid or small interfering RNA, respectively. After the application of the specific CaN inhibitor cyclosporine A (CsA), the changes in NP65 expression did not produce subsequent alterations in the expression of GABAAR-α2, CaN, or phosphorylated NFATc4 proteins. CONCLUSIONS: NP65 modulates the level of GABAAR-α2 through the CaN-NFATc4 signaling pathway, which may serve as the underlying mechanism of NP.

Quantitative assessment of left ventricular myocardial work in patients with different types of atrial fibrillation by non-invasive pressure-strain loop technique.

OBJECTIVE: This study aimed to analyze myocardial work in patients with atrial fibrillation (AF) using a noninvasive pressure strain loop (PSL) technique to provide a basis for the quantitative assessment of left ventricular (LV) systolic function. METHODS: LV myocardial work of 107 AF patients (56 with paroxysmal atrial fibrillation and 51 with persistent atrial fibrillation) and 55 healthy individuals were assessed by the noninvasive PSL and then compared. RESULTS: Global longitudinal strain (GLS) in absolute values, global work index (GWI), global constructive work (GCW), and global work efficiency (GWE) were significantly lower in the AF group than control group, whereas peak strain dispersion (PSD) and global wasted work (GWW) were significantly higher (P < .05). Further subdivision according to the AF type revealed that, compared with the controls, GLS in absolute values and GWE decreased significantly; PSD and GWW increased significantly in the paroxysmal AF group (P < .05). Nevertheless, GWI and GCW were not significantly different between paroxysmal AF and control groups (P > .05). Compared to paroxysmal AF, persistent AF induced a further decrease in absolute GLS and GWE and a further increase in GWW (P < .05), but PSD did not increase further (P > .05). Multiple linear regression analysis showed that GWI and GCW were independently associated with systolic blood pressure. GWW was associated with types of AF and left atrial volume index (LAVI). GWE was correlated with age, types of AF, disease duration, and LAVI. Receiver operating characteristic curve analysis showed that the area under the curve predicting myocardial injury was higher for GWE and GWW than for GLS (area under the curve:  .880,  .846, and  .821, respectively). CONCLUSIONS: Non-invasive PSL can quantitatively assess LV systolic function in patients with different kinds of AF and detect early subclinical myocardial injury in patients with paroxysmal AF. GWE and GWW outperform GLS and LV ejection fraction when assessing myocardial injury. Systolic blood pressure, type of AF, LVAI, disease duration, and age may be associated with myocardial injury in patients with AF.

Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients.

BACKGROUND: Hypertension usually clusters with multiple comorbidities. However, the association between cardiometabolic multimorbidity (CMM) and mortality in hypertensive patients is unclear. This study aimed to investigate the association between CMM and all-cause and cardiovascular disease (CVD) mortality in Chinese patients with hypertension. METHODS: The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors (CONSIDER), which comprised 5006 participants aged 19-91 years. CMM was defined as the presence of one or more of the following morbidities: diabetes mellitus, dyslipidemia, chronic kidney disease, coronary heart disease, and stroke. Cox proportional hazard models were used to calculate the hazard ratios (HR) with 95% CI to determine the association between the number of CMMs and both all-cause and CVD mortality. RESULTS: Among 5006 participants [mean age: 58.6 ± 10.4 years, 50% women (2509 participants)], 76.4% of participants had at least one comorbidity. The mortality rate was 4.57, 4.76, 8.48, and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one, two, and three or more morbidities, respectively. In the fully adjusted model, hypertensive participants with two cardiometabolic diseases (HR = 1.52, 95% CI: 1.09-2.13) and those with three or more cardiometabolic diseases (HR = 2.44, 95% CI: 1.71-3.48) had a significantly elevated risk of all-cause mortality. The findings were similar for CVD mortality but with a greater increase in risk magnitude. CONCLUSIONS: In this study, three-fourths of hypertensive patients had CMM. Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients, suggesting more intensive treatment and control in this high-risk patient group.

Mitochondrial Dysfunction of Peripheral Platelets as a Predictive Biomarker for Postoperative Delirium in Elderly Patients.

OBJECTIVE: To determine the association between the preoperative Bioenergetic Health Index (BHI) of platelets and the occurrence of postoperative delirium (POD) in elderly patients. METHODS: Elderly patients scheduled for major abdominal surgery under general anesthesia were included. The presence of POD was assessed within the 3 days after surgery. Seahorse XF analysis and transmission electron microscopy were utilized to evaluate the mitochondrial metabolism and morphology of platelets. RESULTS: A total of 20 out of 162 participants developed POD. Participants with POD showed lower preoperative Mini-Mental State Examination scores and total protein levels, fewer educational years, longer surgery duration, higher mean platelet volume, and lower platelet BHI compared with those without POD. Damaged mitochondria with swollen appearance and distorted cristae was detected in platelets from participants with POD. Preoperative platelet BHI was independently associated with the occurrence of POD after adjusting for age, education, preoperative Mini-Mental State Examination score, preoperative mean platelet volume and total protein levels, surgical type and duration, and lymphocyte counts on the first postoperative day (OR 0.11, 95% CI 0.03-0.37, p < 0.001). The areas under the receiver operating curves for predicting POD were 0.83 (95% CI 0.76-0.88) for platelet BHI. It showed a sensitivity of 85.00% and specificity of 73.24%, with an optimal cutoff value of 1.61. Using a serial combination (mean platelet volume followed by BHI) yielded a sensitivity of 80.00% and specificity of 82.39%. INTERPRETATION: Preoperative platelet BHI was independently associated with the occurrence of POD in elderly patients and has the potential as a screening biomarker for POD risk. ANN NEUROL 2024.

Tamarind seed polysaccharide-guar gum buccal films loaded with resveratrol-bovine serum albumin nanoparticles: Preparation, characterization, and mucoadhesiveness assessment.

Mucoadhesive films based on tamarind seed polysaccharide and guar gum (TSP-GG) were formulated for buccal delivery of resveratrol. Resveratrol-bovine serum albumin nanoparticles (Res-BSA) were prepared and dispersed in TSP-GG to improve its buccal mucoadhesiveness. The impregnation of Res-BSA induced the dense internal structures of TSP-GG and improved its strength and rigidity. Structural characterization showed that resveratrol existed in an amorphous state in the films containing Res-BSA, and hydrogen bonding was formed between Res-BSA and the film matrices. The films containing Res-BSA exhibited good uniformity in thickness, weight, and resveratrol content, and their surface pH was near neutral, ranging between 6.78 and 7.09. Increasing Res-BSA content reduced the water contact angle of TSP-GG (from 75.9° to 59.6°). The swelling and erosion studies indicated the favorable hydration capacity and erosion resistance of the films containing Res-BSA. Additionally, the addition of Res-BSA imparted enhanced ex vivo mucoadhesive force, in the range of 1.53 N to 1.98 N, and extended ex vivo residence time, between 17.9 h and 18.9 h, to TSP-GG. The current study implied that the composite systems of TSP-GG and Res-BSA may be a novel platform for buccal mucosal delivery of resveratrol.

Roles of AFAP1-AS1 in Gynecology and Urogenital System.

BACKGROUND: Human disease onset and progression are strongly associated with aberrant long noncoding RNA (lncRNA) expression, highlighting the functional regulatory role of lncRNA. Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1), a member of lncRNAs, is located on the antisense strand of Actin filament-associated protein 1 (AFAP1). METHODS: We conducted a comprehensive review of AFAP1-AS1's functions in gynecology and urogenital systems using the "PubMed" database. RESULTS: Our analysis reveals that AFAP1-AS1 is overexpressed and engages in the initiation and process of gynecological and urogenital diseases. The regulatory mechanisms employed by AFAP1-AS1 involve four major strategies: gene-level effects, competition for microRNA (miRNA) repression, protein binding, participation in signaling networks that influence cellular processes such as proliferative phenotype, migration, invasiveness, epithelial-mesenchymal transition (EMT), cycle regulation, drug resistance, and more. Furthermore, AFAP1-AS1 is implicated in guiding clinicopathological characteristics. CONCLUSION: AFAP1-AS1 holds promise as a potent diagnostics and treatment option for gynecological and genitourinary systems in the future.

bay/ortho-Octa-substituted Perylene: A Versatile Building Block toward Novel Polycyclic (Hetero)Aromatic Hydrocarbons.

ConspectusPolycyclic (hetero)aromatic hydrocarbons (PAHs) have emerged as a focal point in current interdisciplinary research, spanning the realms of chemistry, physics, and materials science. Possessing distinctive optical, electronic, and magnetic properties, these π-functional materials exhibit significant potential across diverse applications, including molecular electronic devices, organic spintronics, and biomedical functions, among others. Despite the extensive documentation of various PAHs over the decades, the efficient and precise synthesis of π-extended PAHs remains a formidable challenge, hindering their broader application. This challenge is primarily attributed to the intricate and often elusive nature of their synthesis, compounded by issues related to low solubility and unfavored stability.The development of π-building blocks that can be facilely and modularly transformed into diverse π-frameworks constitutes a potent strategy for the creation of novel PAH materials. For instance, based on the classic perylene diimide (PDI) unit, researchers such as Würthner, Wang, and Nuckolls have successfully synthesized a plethora of structurally diverse PAHs, as well as numerous other π-functional materials. However, until now the availability of such versatile building blocks is still severely limited, especially for those simultaneously having a facile preparation process, adequate solubilizing groups, favored material stability, and critically, rich possibilities for structural extension spaces.In this Account, we present an overview of our invention of a highly versatile bay-/ortho-octa-substituted perylene building block, designated as Per-4Br, for the construction of a series of novel PAH scaffolds with tailor-made structures and rich optoelectronic and magnetic properties. First, starting with a brief discussion of current challenges associated with the bottom-up synthesis of π-extended PAHs, we rationalize the key features of Per-4Br that enable facile access to new PAH molecules including its ease of large-scale preparation, favored material stability and solubility, and multiple flexible reaction sites, with a comparison to the PDI motif. Then, we showcase our rational design and sophisticated synthesis of a body of neutral or charged, closed- or open-shell, curved, or planar PAHs via controlled annulative π-extensions in different directions such as peripheral, diagonal, or multiple dimensions of the Per-4Br skeleton. In this part, the fundamental structure-property relationships between molecular conformations, electronic structures, and self-assembly behaviors of these PAHs and their unique physiochemical properties such as unusual open-shell ground states, global aromaticity, state-associated/stimuli-responsive magnetic activity, and charge transport characteristics will be emphatically elaborated. Finally, we offer our perspective on the continued advancement of π-functional materials based on Per-4Br, which, we posit, may stimulate heightened research interest in the versatile structural motifs typified by Per-4Br, consequently catalyzing further progress in the realm of organic π-functional materials.

IRF4 induces M1 macrophage polarization and aggravates ulcerative colitis progression by the Bcl6-dependent STAT3 pathway.

Ulcerative colitis (UC) is an idiopathic chronic intestinal inflammation. An increasing body of evidence shows that macrophages play an important role in the pathogenesis of UC. Interferon regulatory factor 4 (IRF4) is crucial for the development of autoimmune diseases via regulating immune cells. This research was designed to explore the function of IRF4 in UC and its association with macrophage polarization. The in vitro model of UC was established by stimulating colonic epithelial cells with tumor necrosis factor α (TNF-α). A mouse model of UC was constructed by injecting C57BL/6 mice with dextran sulfate sodium salt. Flow cytometry was used to assess percentage of CD11b+ CD86+ and CD11b+ CD206+ cells in bone marrow macrophages. Occult blood tests were used to detect hematochezia. Hematoxylin and eosin staining assay was used to assess colon pathological changes. Enzyme-linked immunosorbent assay (ELISA) was used to detect concentrations of inflammatory cytokines. The interaction of IRF4 and B-cell lymphoma 6 (Bcl6) was confirmed using GST pull-down and coimmunoprecipitation assays. Our findings revealed that IRF4 promoted cell apoptosis and stimulated M1 macrophage polarization in vitro. Furthermore, IRF4 aggravated symptoms of the mouse model of UC and aggravated M1 macrophage polarization in vivo. IRF4 negatively regulated Bcl6 expression. Downregulation of Bcl6 promoted apoptosis and M1 macrophage polarization in the presence of IRF4 in vitro and in vivo. Moreover, Bcl6 positively mediated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In conclusion, IRF4 aggravated UC progression through promoting M1 macrophage polarization via Bcl6/JAK2/STAT3 pathway. These findings suggested that IRF4 might be a good target to competitively inhibit or to treat with UC.

Pharmacological modulation of RB1 activity mitigates resistance to neoadjuvant chemotherapy in locally advanced rectal cancer.

Resistance to neoadjuvant chemotherapy leads to poor prognosis of locally advanced rectal cancer (LARC), representing an unmet clinical need that demands further exploration of therapeutic strategies to improve clinical outcomes. Here, we identified a noncanonical role of RB1 for modulating chromatin activity that contributes to oxaliplatin resistance in colorectal cancer (CRC). We demonstrate that oxaliplatin induces RB1 phosphorylation, which is associated with the resistance to neoadjuvant oxaliplatin-based chemotherapy in LARC. Inhibition of RB1 phosphorylation by CDK4/6 inhibitor results in vulnerability to oxaliplatin in both intrinsic and acquired chemoresistant CRC. Mechanistically, we show that RB1 modulates chromatin activity through the TEAD4/HDAC1 complex to epigenetically suppress the expression of DNA repair genes. Antagonizing RB1 phosphorylation through CDK4/6 inhibition enforces RB1/TEAD4/HDAC1 repressor activity, leading to DNA repair defects, thus sensitizing oxaliplatin treatment in LARC. Our study identifies a RB1 function in regulating chromatin activity through TEAD4/HDAC1. It also provides the combination of CDK4/6 inhibitor with oxaliplatin as a potential synthetic lethality strategy to mitigate oxaliplatin resistance in LARC, whereby phosphorylated RB1/TEAD4 can serve as potential biomarkers to guide the patient stratification.

Microglia Promote Inhibitory Synapse Phagocytosis in the Spinal Cord Dorsal Horn and Modulate Pain-Like Behaviors in a Murine Cancer-Induced Bone Pain Model.

BACKGROUND: The microglial activation has been implicated in cancer-induced bone pain. Recent studies have revealed that microglia mediate synaptic pruning in the central nervous system, where the cluster of differentiation 47-signal regulatory protein α (CD47-SIRPα) axis creates a "don't eat me" signal and elicits an antiphagocytic effect to protect synapses against elimination. To date, the synaptic phagocytosis in microglia has never been investigated in the murine cancer-induced bone pain model. The present experiments sought to explore whether microglia phagocytize synapses in mice with bone cancer pain as well as the possible mechanisms. METHODS: Male C3H/HeN mice were used to induce bone cancer pain. Minocycline and S-ketamine were injected into D14. The number of spontaneous flinches (NSF) and paw withdrawal mechanical thresholds (PWMT) were measured on D0, D4, D7, D10, D14, D21, and D28. Hematoxylin and eosin staining presented bone lesions. Western blotting examined the Gephyrin, CD47, and SIRPα expression. Flow cytometry evaluated the proportion of SIRPα+ cells in the spine. Immunofluorescence and 3-dimensional reconstruction showed the Gephyrin puncta inside microglial lysosomes. RESULTS: Mice embedded with tumor cells induced persistent spontaneous pain and mechanical hyperalgesia. Hematoxylin and eosin staining revealed bone destruction and tumor infiltration in marrow cavities. Microglia underwent a responsive and proliferative burst (t = -16.831, P < .001). Western blotting manifested lowered Gephyrin expression in the tumor group (D4, D7, D10, D14, D21, and D28: P < .001). Immunofluorescence and 3-dimensional reconstruction showed larger volumes of Gephyrin puncta inside microglial lysosomes (t = -23.273, P < .001; t = -27.997, P < .001). Treatment with minocycline or S-ketamine exhibited pain relief and antiphagocytic effects (t = -6.191, P < .001, t = -7.083, P < .001; t = -20.767, P < .001, t = -17.080, P < .001; t = 11.789, P < .001, t = 16.777, P < .001; t = 8.868, P < .001, t = 21.319, P < .001). Last but not least, the levels of CD47 and SIRPα proteins were downregulated (D10: P = .004, D14, D21, and D28: P < .001; D10, D14, D21, and D28: P < .001). Flow cytometry and immunofluorescence substantiated reduced microglial SIRPα (t = 11.311, P < .001; t = 12.189, P < .001). CONCLUSIONS: Microglia-mediated GABAergic synapse pruning in the spinal cord dorsal horn in bone cancer pain mice, which might be associated with the declined CD47-SIRPα signal. Our research uncovered an innovative mechanism that highlighted microglia-mediated synaptic phagocytosis in a murine cancer-induced bone pain model.

Laponite nanoparticle-crosslinked carboxymethyl cellulose-based injectable hydrogels with efficient underwater-specific adhesion for rapid hemostasis.

Tissue adhesives have attracted intense and increasing interest due to their multiple biomedical applications. Despite the rapid development of adhesive hydrogels, huge challenges remain for materials that can ensure strong adhesion and seal hemostasis in aqueous and blood environments. To address this issue, we have developed an innovative design of PAA-based coacervate hydrogel with strong wet adhesion capability through a simple mixture of PAA copolymers with oxidized-carboxymethylcellulose (OCMC), and tannic acid (TA) as the main components, and structurally enhanced with natural clays (Laponite XLG). The absorbed TA provides solid adhesion to dry and wet substrates via multiple interactions, which endows the XLG-enhanced coacervate with the desired underwater adhesive strength. More importantly, the dielectric constant is introduced to evaluate the polarity of the tested samples, which may be used as guidance for the design of mussel-inspired adhesives with even better underwater adhesive properties. In vivo hemorrhage experiments further confirmed that the hydrogel adhesive dramatically shortened the hemostatic time to tens of seconds. Overall, the persistent adhesion and acceptable cytocompatibility of the hydrogel nanocomposite make it a promising alternative suture-free approach for rapid hemostasis at different length scales and is expected to be extended to clinical application for other organ injuries.

Seeking central hopelessness symptoms which direct link to resilience among parents of children with autism spectrum disorder in China-A network perspective.

The intervention process for children with autism spectrum disorder (ASD) is inextricably associated with their parents' mental health problems, such as hopelessness, which may adversely affect resilience and indirectly impact the effectiveness of interventions for their children. Hence, the motivation to help parents of children with ASD reduce hopelessness prompted us to conduct the present study and explore the interrelationship between hopelessness symptoms and resilience. This study evaluated hopelessness and resilience using the Beck Hopelessness Scale (BHS) and the Connor-Davidson Resilience Scale (CD-RISC). Participants met the criteria for their children's ASD diagnosis by a psychiatrist (N = 448; 54.69% mothers; Meanage = 34.59 years, SDage = 4.94 years). Moreover, we used symptom network analysis to examine the variability in network structure between fathers and mothers. The flow function was applied to examine which hopelessness symptoms were directly or indirectly associated with resilience. The results showed that #BHS11 (i.e., unpleasantness-ahead) was the central symptom found in the network structure for all parents and fathers, while #BHS17 (i.e., no-future-satisfaction) was the central symptom in the network structure for mothers. Additionally, #BHS6 ([NOT] expect-to-succeed) was directly and positively associated with resilience in all three network structures (i.e., all parents, fathers, and mothers). The results of the present study provide evidence that influential symptoms should be addressed and offer guidance for further interventions to reduce hopelessness and enhance resilience among parents of children with ASD.

Novel Plastid Genome Characteristics in Fugacium kawagutii and the Trend of Accelerated Evolution of Plastid Proteins in Dinoflagellates.

Typical (peridinin-containing) dinoflagellates possess plastid genomes composed of small plasmids named "minicircles". Despite the ecological importance of dinoflagellate photosynthesis in corals and marine ecosystems, the structural characteristics, replication dynamics, and evolutionary forcing of dinoflagellate plastid genomes remain poorly understood. Here, we sequenced the plastid genome of the symbiodiniacean species Fugacium kawagutii and conducted comparative analyses. We identified psbT-coding minicircles, features previously not found in Symbiodiniaceae. The copy number of F. kawagutii minicircles showed a strong diel dynamics, changing between 3.89 and 34.3 copies/cell and peaking in mid-light period. We found that F. kawagutii minicircles are the shortest among all dinoflagellates examined to date. Besides, the core regions of the minicircles are highly conserved within genus in Symbiodiniaceae. Furthermore, the codon usage bias of the plastid genomes in Heterocapsaceae, Amphidiniaceae, and Prorocentraceae species are greatly influenced by selection pressure, and in Pyrocystaceae, Symbiodiniaceae, Peridiniaceae, and Ceratiaceae species are influenced by both natural selection pressure and mutation pressure, indicating a family-level distinction in codon usage evolution in dinoflagellates. Phylogenetic analysis using 12 plastid-encoded proteins and five nucleus-encoded plastid proteins revealed accelerated evolution trend of both plastid- and nucleus-encoded plastid proteins in peridinin- and fucoxanthin-dinoflagellate plastids compared to plastid proteins of nondinoflagellate algae. These findings shed new light on the structure and evolution of plastid genomes in dinoflagellates, which will facilitate further studies on the evolutionary forcing and function of the diverse dinoflagellate plastids. The accelerated evolution documented here suggests plastid-encoded sequences are potentially useful for resolving closely related dinoflagellates.

Application of cloud server-based machine learning for assisting pathological structure recognition in IgA nephropathy.

BACKGROUND: Machine learning (ML) models can help assisting diagnosis by rapidly localising and classifying regions of interest (ROIs) within whole slide images (WSIs). Effective ML models for clinical decision support require a substantial dataset of 'real' data, and in reality, it should be robust, user-friendly and universally applicable. METHODS: WSIs of primary IgAN were collected and annotated. The H-AI-L algorithm which could facilitate direct WSI viewing and potential ROI detection for clinicians was built on the cloud server of matpool, a shared internet-based service platform. Model performance was evaluated using F1-score, precision, recall and Matthew's correlation coefficient (MCC). RESULTS: The F1-score of glomerular localisation in WSIs was 0.85 and 0.89 for the initial and pretrained models, respectively, with corresponding recall values of 0.79 and 0.83, and precision scores of 0.92 and 0.97. Dichotomous differentiation between global sclerotic (GS) and other glomeruli revealed F1-scores of 0.70 and 0.91, and MCC values of 0.55 and 0.87, for the initial and pretrained models, respectively. The overall F1-score of multiclassification was 0.81 for the pretrained models. The total glomerular recall rate was 0.96, with F1-scores of 0.68, 0.56 and 0.26 for GS, segmental glomerulosclerosis and crescent (C), respectively. Interstitial fibrosis/tubular atrophy lesion similarity between the true label and model predictions was 0.75. CONCLUSIONS: Our results underscore the efficacy of the ML integration algorithm in segmenting ROIs in IgAN WSIs, and the internet-based model deployment is in favour of widespread adoption and utilisation across multiple centres and increased volumes of WSIs.

Recovering from trampling: The role of dauciform roots to functional traits response of Carex filispica in alpine meadow.

In the natural habitats of China, dauciform roots were only described in degraded alpine meadows. It was found that the presence of dauciform roots of Carex filispica was related to the advantage of multiple functional traits after trampling, reflecting short-term resistance. However, the long-term response of dauciform roots to trampling and the recovery of C. filispica with and without dauciform roots to trampling require further studies. In this study, different intensities of trampling (0, 50, 200 and 500 passages) were performed in an alpine meadow. One year later, individuals with and without dauciform roots were separated and their functional traits related to the economic spectrum of leaves and roots were measured as a reflection of recovery from trampling. The results showed that: (1) 1 year after trampling, the number of dauciform roots showed an increase with trampling intensity; (2) 1 year later, there was no significant difference in the response of economic spectrum traits among trampling intensities, or between plants with and without dauciform roots; (3) the number of dauciform roots was positively correlated with the leaf area of both individuals with and without dauciform roots, as well as with the biomass of those without dauciform roots; and (4) plants with more resource-conservative roots showed an advantage after trampling recovery: specifically, plants with dauciform roots showed such an advantage in the control group, which was lost with a leaning towards resource-acquisitive roots and an increased density of dauciform roots once trampled. In contrast, plants without dauciform roots showed a significant advantage of conservative roots only after trampling. In conclusion, the presence of dauciform roots is related to the plants' position on the root economic spectrum, thereby influencing the recovery of C. filispica from trampling. Carex filispica showed strong recovery from trampling after 1 year, which makes it an adequate choice for ecological restoration in alpine meadows. Dauciform roots showed a positive correlation with the aboveground growth of both plants with and without them, however, it requires a lab-controlled study to confirm whether there is indeed a positive effect on the growth of neighbouring plants.

Nonoptimum Temperatures Are More Closely Associated With Fatal Myocardial Infarction Than With Nonfatal Events.

BACKGROUND: Ambient temperatures trigger hospitalisation, mortality, and emergency department visits for myocardial infarction (MI). However, nonoptimum temperature-related risks of fatal and nonfatal MI have not yet been compared. METHODS: From 2007 to 2019, 416,894 MI events (233,071 fatal and 183,823 nonfatal) were identified in Beijing, China. A time-series analysis with a distributed-lag nonlinear model was used to compare the relative and population-attributable risks of fatal and nonfatal MI associated with nonoptimum temperatures. RESULTS: The reference was the optimum temperature of 24.3°C. For single-lag effects, cold (-5.2°C) and heat (29.6°C) effects had associations that persisted for more days for fatal MI than for nonfatal MI. For cumulative-lag effects over 0 to 21 days, cold effects were higher for fatal MI (relative risk [RR] 1.99, 95% confidence interval [CI] 1.68-2.35) than for nonfatal MI (RR 1.60, 95% CI 1.32-1.94) with a P value for difference in effect sizes of 0.048. In addition, heat effects were higher for fatal MI (RR 1.33, 95% CI 1.24-1.44) than for nonfatal MI (RR 0.99, 95% CI 0.91-1.08) with a P value for difference in effect sizes of 0.002. The attributable fraction of nonoptimum temperatures was higher for fatal MI (25.6%, 95% CI 19.7%-30.6%) than for nonfatal MI (19.1%, 95% CI 12.1%-25.0%). CONCLUSIONS: Fatal MI was more closely associated with nonoptimum temperatures than nonfatal MI, as evidenced by single-lag effects that have associations which persisted for more days, higher cumulative-lag effects, and higher attributable risks for fatal MI. Strategies are needed to mitigate the adverse effects of nonoptimum temperatures.

Dauciform roots affect the position of the neighboring plants on the economic spectrum in degraded alpine meadows.

Background and aims: Special root structures that can dissolve insoluble phosphorus locked in soil are supposed to contribute not only to the growing status of themselves but also to the neighbouring plants. However, whether dauciform roots have any effect on the neighbouring plants and how does it respond to meadow degradation had not been studied. Methods: Alpine meadows with different degradation statuses were selected and the functional traits of Carex filispica and the co-occurring species Polygonum viviparum were measured to explore their response to degradation, as well as the response of Polygonum viviparum to the dauciform roots of Carex filispica. Results: The results showed that 1) the number of dauciform roots decreased with the intensifying degradation, positively related to available phosphorus in the soil and negatively related to the aboveground phosphorus of Carex filispica. 2) Carex filispica and Polygonum viviparum are similar in specific leaf area and specific root area, yet different in the phosphorus content. The available phosphorus in the soil was negatively related to the aboveground phosphorus of Carex filispica and positively related to that of Polygonum viviparum. 3) When lightly degraded, the proportion of dauciform roots had positive effects on the aboveground resource-acquiring traits of Polygonum viviparum, which were no longer significant at heavy degradation. 4) Polygonum viviparum and Carex filispica without dauciform roots have similar performance: a decrease of belowground carbon with the increasing degradation, and a trend toward resource conservation with the increasing proportion of dauciform roots, which did not exist in Carex filispica with dauciform roots. Conclusion: Our study found that dauciform roots had a beneficial effect on the resource acquisition of their neighbouring plants. However, due to the uncontrollable nature of natural habitats, whether this effect is stable and strong enough to be performed in ecological restoration requires further lab-controlled studies.

A Protocol for Digitalized Collection of Traditional Chinese Medicine (TCM) Pulse Information Using Bionic Pulse Diagnosis Equipment.

Pulse diagnosis equipment used in Traditional Chinese Medicine (TCM) has long been developed for collecting pulse information and in TCM research. However, it is still difficult to implement pulse taking automatically or efficiently in clinical practice. Here, we present a digital protocol for TCM pulse information collection based on bionic pulse diagnosis equipment, which ensures high efficiency, reliability and data integrity of pulse diagnosis information. A four-degree-of-freedom pulse taking platform together with a wrist bracket can satisfy the spatial positioning and angle requirements for individually adaptive pulse acquisition. Three-dimensional reconstruction of a wrist surface and an image localization model are combined to provide coordinates of the acquisition position and detection direction automatically. Three series elastic joints can not only simulate the TCM pulse taking method that "Three fingers in a straight line, the middle finger determining the 'Guan' location and finger pulp pressing on the radial artery," but also simultaneously carry out the force-controlled multi-gradient pressing process. In terms of pulse information integrity, this proposed protocol can generate rich pulse information, including basic individual information, pulse localization distribution, multi-gradient dynamic pulse force time series, and objective pulse parameters, which can help establish the fundamental data sets that are required as the pulse phenotype for subsequent comprehensive analysis of pulse diagnosis. The implementation of this scheme is beneficial to promote the standardization of the digitalized collection of pulse information, the effectiveness of detecting abnormal health status, and the promotion of the fundamental and clinical research of TCM, such as TCM pulse phenomics.