Porcine circovirus type 2 infection promotes the SUMOylation of nucleophosmin-1 to facilitate the viral circular single-stranded DNA replication.

The mechanism of genome DNA replication in circular single-stranded DNA viruses is currently a mystery, except for the fact that it undergoes rolling-circle replication. Herein, we identified SUMOylated porcine nucleophosmin-1 (pNPM1), which is previously reported to be an interacting protein of the viral capsid protein, as a key regulator that promotes the genome DNA replication of porcine single-stranded DNA circovirus. Upon porcine circovirus type 2 (PCV2) infection, SUMO2/3 were recruited and conjugated with the K263 site of pNPM1's C-terminal domain to SUMOylate pNPM1, subsequently, the SUMOylated pNPM1 were translocated in nucleoli to promote the replication of PCV2 genome DNA. The mutation of the K263 site reduced the SUMOylation levels of pNPM1 and the nucleolar localization of pNPM1, resulting in a decrease in the level of PCV2 DNA replication. Meanwhile, the mutation of the K263 site prevented the interaction of pNPM1 with PCV2 DNA, but not the interaction of pNPM1 with PCV2 Cap. Mechanistically, PCV2 infection increased the expression levels of Ubc9, the only E2 enzyme involved in SUMOylation, through the Cap-mediated activation of ERK signaling. The upregulation of Ubc9 promoted the interaction between pNPM1 and TRIM24, a potential E3 ligase for SUMOylation, thereby facilitating the SUMOylation of pNPM1. The inhibition of ERK activation could significantly reduce the SUMOylation levels and the nucleolar localization of pNPM1, as well as the PCV2 DNA replication levels. These results provide new insights into the mechanism of circular single-stranded DNA virus replication and highlight NPM1 as a potential target for inhibiting PCV2 replication.

PoRVA G9P[23] and G5P[7] infections differentially promote PEDV replication by reprogramming glutamine metabolism.

PoRVA and PEDV coinfections are extremely common in clinical practice. Although coinfections of PoRVA and PEDV are known to result in increased mortality, the underlying mechanism remains unknown. Here, we found that PoRVA infection promoted PEDV infection in vivo and in vitro and that PoRVA G9P[23] (RVA-HNNY strain) enhanced PEDV replication more significantly than did PoRVA G5P[7] (RVA-SXXA strain). Metabolomic analysis revealed that RVA-HNNY more efficiently induced an increase in the intracellular glutamine content in porcine small intestinal epithelial cells than did RVA-SXXA, which more markedly promoted ATP production to facilitate PEDV replication, whereas glutamine deprivation abrogated the effect of PoRVA infection on promoting PEDV replication. Further studies showed that PoRVA infection promoted glutamine uptake by upregulating the expression of the glutamine transporter protein SLC1A5. In SLC1A5 knockout cells, PoRVA infection neither elevated intracellular glutamine nor promoted PEDV replication. During PoRVA infection, the activity and protein expression levels of glutamine catabolism-related enzymes (GLS1 and GLUD1) were also significantly increased promoting ATP production through glutamine anaplerosis into the TCA cycle. Consistent with that, siRNAs or inhibitors of GLS1 and GLUD1 significantly inhibited the promotion of PEDV replication by PoRVA. Notably, RVA-HNNY infection more markedly promoted SLC1A5, GLS1 and GLUD1 expression to more significantly increase the uptake and catabolism of glutamine than RVA-SXXA infection. Collectively, our findings illuminate a novel mechanism by which PoRVA infection promotes PEDV infection and reveal that the modulation of glutamine uptake is key for the different efficiencies of PoRVA G9P[23] and PoRVA G5P[7] in promoting PEDV replication.

Rapid conversion of porcine pluripotent stem cells into macrophages with chemically defined conditions.

A renewable source of porcine macrophages derived from pluripotent stem cells (PSCs) would be a valuable alternative to primary porcine alveolar macrophages (PAMs) in the research of host-pathogen interaction mechanisms. We developed an efficient and rapid protocol, within 11 days, to derive macrophages from porcine PSCs (pPSCs). The pPSC-derived macrophages (pPSCdMs) exhibited molecular and functional characteristics of primary macrophages. The pPSCdMs showed macrophage-specific surface protein expression and macrophage-specific transcription factors, similar to PAMs. The pPSCdMs also exhibited the functional characteristics of macrophages, such as endocytosis, phagocytosis, porcine respiratory and reproductive syndrome virus infection and the response to lipopolysaccharide stimulation. Furthermore, we performed transcriptome sequencing of the whole differentiation process to track the fate transitions of porcine PSCs involved in the signaling pathway. The activation of transforming growth factor beta signaling was required for the formation of mesoderm and the inhibition of the transforming growth factor beta signaling pathway at the hematopoietic endothelium stage could enhance the fate transformation of hematopoiesis. In summary, we developed an efficient and rapid protocol to generate pPSCdMs that showed aspects of functional maturity comparable with PAMs. pPSCdMs could provide a broad prospect for the platforms of host-pathogen interaction mechanisms.

A novel RIPK1 inhibitor reduces GVHD in mice via a nonimmunosuppressive mechanism that restores intestinal homeostasis.

Intestinal epithelial cells (IECs) are implicated in the propagation of T-cell-mediated inflammatory diseases, including graft-versus-host disease (GVHD), but the underlying mechanism remains poorly defined. Here, we report that IECs require receptor-interacting protein kinase-3 (RIPK3) to drive both gastrointestinal (GI) tract and systemic GVHD after allogeneic hematopoietic stem cell transplantation. Selectively inhibiting RIPK3 in IECs markedly reduces GVHD in murine intestine and liver. IEC RIPK3 cooperates with RIPK1 to trigger mixed lineage kinase domain-like protein-independent production of T-cell-recruiting chemokines and major histocompatibility complex (MHC) class II molecules, which amplify and sustain alloreactive T-cell responses. Alloreactive T-cell-produced interferon gamma enhances this RIPK1/RIPK3 action in IECs through a JAK/STAT1-dependent mechanism, creating a feed-forward inflammatory cascade. RIPK1/RIPK3 forms a complex with JAK1 to promote STAT1 activation in IECs. The RIPK1/RIPK3-mediated inflammatory cascade of alloreactive T-cell responses results in intestinal tissue damage, converting the local inflammation into a systemic syndrome. Human patients with severe GVHD showed highly activated RIPK1 in the colon epithelium. Finally, we discover a selective and potent RIPK1 inhibitor (Zharp1-211) that significantly reduces JAK/STAT1-mediated expression of chemokines and MHC class II molecules in IECs, restores intestinal homeostasis, and arrests GVHD without compromising the graft-versus-leukemia (GVL) effect. Thus, targeting RIPK1/RIPK3 in IECs represents an effective nonimmunosuppressive strategy for GVHD treatment and potentially for other diseases involving GI tract inflammation.

HDAC3 promotes Sertoli cell maturation and maintains the blood-testis barrier dynamics.

Germ cell development depends on the capacity of somatic Sertoli cells to undergo differentiation into a mature state and establish a germ cell-specific blood-testis barrier (BTB). The BTB structure confers an immunological barrier for meiotic and postmeiotic germ cells, and its dynamic permeability facilitates a transient movement of preleptotene spermatocytes through BTB to enter meiosis. However, the regulatory factors involved in Sertoli cell maturation and how BTB dynamics coordinate germ cell development remain unclear. Here, we found a histone deacetylase HDAC3 abundantly expresses in Sertoli cells and localizes in both cytoplasm and nucleus. Sertoli cell-specific Hdac3 knockout in mice causes infertility with compromised integrity of blood-testis barrier, leading to germ cells unable to traverse through BTB and an accumulation of preleptotene spermatocytes in juvenile testis. Mechanistically, nuclear HDAC3 regulates the expression program of Sertoli cell maturation genes, and cytoplasmic HDAC3 forms a complex with the gap junction protein Connexin 43 to modulate the BTB integrity and dynamics through regulating the distribution of tight junction proteins. Our findings identify HDAC3 as a critical regulator in promoting Sertoli cell maturation and maintaining the homeostasis of the blood-testis barrier.

MicroRNA let-7c-5p Alleviates in Hepatocellular Carcinoma by Targeting Enhancer of Zeste Homolog 2: A Study Intersecting Bioinformatic Analysis and Validated Experiments.

Enhancer of zeste homolog 2 (EZH2)gene has a prognostic role in hepatocellular carcinoma (HCC). This study aimed to identify the role of microRNAs (miRNAs) let-7c-5p by targeting EZH2 in HCC. We downloaded gene and miRNA RNA-seq data from The Cancer Genome Atlas (TCGA) database. Differences in EZH2 expression between different groups were analyzed and the association of EZH2 expression with HCC prognosis was detected using Cox regression analysis. The miRNA-EZH2-pathway network was constructed. Dual-luciferase reporter assay was performed to detect the hsa-let-7c-5p-EZH2. Cell proliferation, migration, invasion, and apoptosis were detected by CCK-8, Wound healing, Transwell, and Flow cytometry, respectively. RT-qPCR and Western blot were used to detect the expression of let-7c-5p and EZH2. EZH2 was upregulated in HCC tumors (P < 0.0001). Cox regression analysis showed that TCGA HCC patients with high EZH2 expression levels showed a short survival time [hazard ratio (HR) = 1.677, 95% confidence interval (CI) 1.316-2.137; P < 0.0001]. Seven miRNAs were negatively correlated with EZH2 expression and were significantly downregulated in HCC tumor samples (P < 0.0001), in which hsa-let-7c-5p was associated with prognosis in HCC (HR = 0.849 95% CI 0.739-0.975; P = 0.021). We identified 14 immune cells that showed significant differences in EZH2 high- and low-expression groups. Additionally, let-7c-5p inhibited HCC cell proliferation, migration, and invasion and reversed the promoted effects of EZH2 on HCC cell malignant characteristics. hsa-let-7c-5p-EZH2 significantly suppressed HCC malignant characteristics, which can be used for HCC prognosis.

Bcl3 Phosphorylation by Akt, Erk2, and IKK Is Required for Its Transcriptional Activity.

Unlike prototypical IκB proteins, which are inhibitors of NF-κB RelA, cRel, and RelB dimers, the atypical IκB protein Bcl3 is primarily a transcriptional coregulator of p52 and p50 homodimers. Bcl3 exists as phospho-protein in many cancer cells. Unphosphorylated Bcl3 acts as a classical IκB-like inhibitor and removes p50 and p52 from bound DNA. Neither the phosphorylation site(s) nor the kinase(s) phosphorylating Bcl3 is known. Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA. Cells expressing the S114A/S446A mutant have cellular proliferation and migration defects. This work links Akt and MAPK pathways to NF-κB through Bcl3 and provides mechanistic insight into how Bcl3 functions as an oncoprotein through collaboration with IKK1/2, Akt, and Erk2.

Research progress on the roles of dopamine and dopamine receptors in digestive system diseases.

Dopamine (DA) is a neurotransmitter synthesized in the human body that acts on multiple organs throughout the body, reaching them through the blood circulation. Neurotransmitters are special molecules that act as messengers by binding to receptors at chemical synapses between neurons. As ligands, they mainly bind to corresponding receptors on central or peripheral tissue cells. Signalling through chemical synapses is involved in regulating the activities of various body systems. Lack of DA or a decrease in DA levels in the brain can lead to serious diseases such as Parkinson's disease, schizophrenia, addiction and attention deficit disorder. It is widely recognized that DA is closely related to neurological diseases. As research on the roles of brain-gut peptides in human physiology and pathology has deepened in recent years, the regulatory role of neurotransmitters in digestive system diseases has gradually attracted researchers' attention, and research on DA has expanded to the field of digestive system diseases. This review mainly elaborates on the research progress on the roles of DA and DRs related to digestive system diseases. Starting from the biochemical and pharmacological properties of DA and DRs, it discusses the therapeutic value of DA- and DR-related drugs for digestive system diseases.

Chemically synthesized osteocalcin alleviates NAFLD via the AMPK-FOXO1/BCL6-CD36 pathway.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. Osteocalcin plays an important role in energy metabolism. In this study, we investigated the mechanism of action of chemically synthesized osteocalcin (csOCN) in ameliorating NAFLD. We demonstrated for the first time that csOCN attenuates lipid accumulation in the liver and hepatocytes by modulating CD36 protein expression. In addition, we found that the expression of p-AMPK, FOXO1 and BCL6 decreased and the expression of CD36 increased after OA/PA induction compared to the control group, and these effects were reversed by the addition of csOCN. In contrast, the therapeutic effect of csOCN was inhibited by the addition of AMPK inhibitors and BCL6 inhibitors. This finding suggested that csOCN regulates CD36 expression via the AMPK-FOXO1/BCL6 axis. In NAFLD mice, oral administration of csOCN also activated the AMPK pathway and reduced CD36 expression. Molecular docking revealed that osteocalcin has a docking site with CD36. Compared to oleic acid and palmitic acid, osteocalcin bound more strongly to CD36. Laser confocal microscopy results showed that osteocalcin colocalized with CD36 at the cell membrane. In conclusion, we demonstrated the regulatory role of csOCN in fatty acid uptake pathways for the first time; it regulates CD36 expression via the AMPK-FOXO1/BCL6 axis to reduce fatty acid uptake, and it affects fatty acid transport by may directly binding to CD36. There are indications that csOCN has potential as a CD36-targeted drug for the treatment of NAFLD.

A transcriptional repressor HVA regulates vascular bundle formation through auxin transport in Arabidopsis stem.

Vascular bundles transport water and photosynthate to all organs, and increased bundle number contributes to crop lodging resistance. However, the regulation of vascular bundle formation is poorly understood in the Arabidopsis stem. We report a novel semi-dominant mutant with high vascular activity, hva-d, showing increased vascular bundle number and enhanced cambium proliferation in the stem. The activation of a C2H2 zinc finger transcription factor, AT5G27880/HVA, is responsible for the hva-d phenotype. Genetic, biochemical, and fluorescent microscopic analyses were used to dissect the functions of HVA. HVA functions as a repressor and interacts with TOPLESS via the conserved Ethylene-responsive element binding factor-associated Amphiphilic Repression motif. In contrast to the HVA activation line, knockout of HVA function with a CRISPR-Cas9 approach or expression of HVA fused with an activation domain VP16 (HVA-VP16) resulted in fewer vascular bundles. Further, HVA directly regulates the expression of the auxin transport efflux facilitator PIN1, as a result affecting auxin accumulation. Genetics analysis demonstrated that PIN1 is epistatic to HVA in controlling bundle number. This research identifies HVA as a positive regulator of vascular initiation through negatively modulating auxin transport and sheds new light on the mechanism of bundle formation in the stem.

The emerging role of cysteine-rich peptides in pollen-pistil interaction.

Unlike early land plants, flowering plants have evolved a pollen tube that transport a pair of non-motile sperm cells to the female gametophyte. This process, known as siphonogamy, was first observed in gymnosperms and later become prevalent in angiosperms. However, the precise molecular mechanisms underlying the male-female interactions remain enigmatic. From the pollen grain's landing on the stigma to gametes fusion, the male part needs to pass various tests: How does the stigma distinguish between compatible and incompatible pollen? What mechanisms guide pollen tube towards the ovule? What factors trigger pollen tube rupture? How is polyspermy prevented? And how does the sperm cell ultimately reach the egg? Successful male-female communications is essential for surmounting these challenges, with cysteine-rich peptides (CRPs) playing a pivotal role in these dialogues. In this review, we summarize the characteristics of four distinct classes of CRPs and then we systematically review the recent progresses of the role of CRPs in four crucial stages of pollination and fertilization. Finally, we conclude by considering the potential applications of this knowledge in crop breeding, and suggesting avenues for future research.

GluOC promotes proliferation and metastasis of TNBC through the ROCK1 signaling pathway.

BACKGROUND: Triple negative breast cancer (TNBC) is a type of breast cancer that is negative for oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, is highly malignant and aggressive, lacks of corresponding targeted therapy, and has a relatively poor prognosis. Therefore, understanding the mechanism of TNBC development and formulating effective treatment strategies for inducing cell death are still urgent tasks in the treatment of TNBC. Research has shown that uncarboxylated osteocalcin can promote the proliferation of prostate cancer, lung adenocarcinoma and TNBC cells, but the mechanism by which GluOC affects TNBC growth and metastasis needs further study. METHODS: MDA-MB-231 breast cancer cells were used for in vitro cell analysis. Key target molecules or pathways were identified by RNA sequencing, and migration ability was detected by scratch assays, Transwell assays, cell adhesion assays and western blot analysis. Fluorescence staining, colony detection, qRT‒PCR and flow cytometry were used to detect apoptosis, oxidative stress, the cell cycle and the stemness of cancer cells, and a xenotransplantation model in BALB/C nude mice was used for in vivo analysis. RESULTS: This study demonstrated that GluOC facilitates the migration of MDA-MB-231 breast cancer cells through the ROCK1/MYPT1/MLC2 signalling pathway and promotes the proliferation of TNBC cells via the ROCK1/JAK2/PIK3CA/AKT signalling pathway. Experiments in nude mice demonstrated that GluOC promoted tumour cell proliferation and metastasis in tumour-bearing mice, which further clarified the molecular mechanism of TNBC growth and invasion. CONCLUSION: Our findings highlight the importance of GluOC in driving TNBC progression and its association with poor patient outcomes. This study clarifies the functional effects of GluOC on TNBC growth, providing insight into the molecular basis of TNBC and potentially providing new ideas for developing targeted therapies to improve patient outcomes.

High salt activates p97 to reduce host antiviral immunity by restricting Viperin induction.

High-salt diets have recently been implicated in hypertension, cardiovascular disease, and autoimmune disease. However, whether and how dietary salt affects host antiviral response remain elusive. Here, we report that high salt induces an instant reduction in host antiviral immunity, although this effect is compromised during a long-term high-salt diet. Further studies reveal that high salt stimulates the acetylation at Lys663 of p97, which promotes the recruitment of ubiquitinated proteins for proteasome-dependent degradation. p97-mediated degradation of the deubiquitinase USP33 results in a deficiency of Viperin protein expression during viral infection, which substantially attenuates host antiviral ability. Importantly, switching to a low-salt diet during viral infection significantly enhances Viperin expression and improves host antiviral ability. These findings uncover dietary salt-induced regulation of ubiquitinated cellular proteins and host antiviral immunity, and could offer insight into the daily consumption of salt-containing diets during virus epidemics.

Conformal sulfidation of HKUST-1 for constructing porous Cu2S/CuO octahedrons realizing highly sensitive non-enzymatic glucose detection.

Metal-organic frameworks (MOFs) are believed to be promising precursors for constructing novel and efficient catalysts for glucose sensing. Herein, HKUST-1 precursors are first fabricated using a one-pot hydrothermal approach, and then HKUST-1 is converted into porous Cu2S/CuO octahedrons through conformal sulfidation with the help of OH-ions. The as-obtained Cu2S/CuO composite can provide rich electrochemical active sites and promoted electric transfer kinetics. Benefiting from these combined merits, the as-fabricated Cu2S/CuO composite is confirmed to be a high-performance catalyst, with high sensitivities of 8269.45 and 4140.82µA mM-1cm-2in the corresponding ranges of 0.05 ∼ 0.6 mM and 0.6 ∼ 1.2 mM, respectively. Moreover, the as-prepared electrode materials possess good anti-interference ability, reproducibility and long-term stability. This work opens up new avenues for the design and preparation of transition metal sulfide composites.

Clinical characteristics and influencing factors of severe fever with thrombocytopenia syndrome complicated by viral myocarditis: a retrospective study.

OBJECTIVE: This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors. METHODS: Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM. RESULTS: SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P < 0.05). Multivariate analysis identified elevated LDH upon admission (OR = 1.004, 95% CI: 1-1.008, P = 0.050), elevated NT-proBNP (OR = 1.005, 95% CI: 1.001-1.008, P = 0.007), and consciousness disorders (OR = 112.852, 95% CI: 3.676 ~ 3464.292, P = 0.007) as independent risk factors for SFTS-SVM. LDH and NT-proBNP had AUCs of 0.728 and 0.744, respectively, in predicting SFTS-SVM. Critical values of LDH (> 978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM. CONCLUSION: Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds.

Systemic inflammatory response syndrome in patients with severe fever with thrombocytopenia syndrome: prevalence, characteristics, and impact on prognosis.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated inflammatory response is associated with disease pathogenesis and mortality in patients with SFTS. This investigation aimed to evaluate the prevalence and characteristics of systemic inflammatory response syndrome (SIRS), and its impact on prognosis. METHODS: Data on demographic characteristics, comorbid conditions, clinical manifestations, laboratory parameters, and survival time of patients with SFTS were collected. Patients were divided into the non-SIRS and SIRS groups according to the presence of SIRS, then their clinical data were compared. RESULTS: A total of 290 patients diagnosed with SFTS were retrospectively enrolled, including 126(43.4%) patients with SIRS. Patients in the non-survivor group had more prevalence of SIRS than patients in the survivor group (P < 0.001), and SIRS (adjusted OR 2.885, 95% CI 1.226-6.786; P = 0.005) was shown as an independent risk factor for prognosis of patients with SFTS. Compared with patients without SIRS, patients with SIRS had lower WBC and neutrophils counts, and fibrinogen levels, but higher AST, LDH, amylase, lipase, CK, CK-MB, troponin I, APTT, thrombin time, D-dimer, CRP, IL-6, SAA levels, and viral load. The cumulative survival rate of patients with SIRS was significantly lower than that of patients without SIRS. Patients with SIRS also showed a higher incidence of bacterial or fungal infections than patients without SIRS. CONCLUSIONS: SIRS is highly frequent in patients with SFTS, and it is associated with high mortality.

Improving the stability, foliar utilization and biological activity of imidacloprid delivery systems: Size effect of nanoparticles.

Nanotechnology could improve the effectiveness and functionality of pesticides, but the size effect of nanopesticides on formulation performance and the related mechanisms have yet to be explored, hindering the precise design and development of efficient and eco-friendly nanopesticides. In this study, two non-carrier-coated imidacloprid formulations (Nano-IMI and Micro-IMI) with identical composition but varying particle size characteristics were constructed to exclude other interferences in the size effect investigation. Nano-IMI and Micro-IMI both exhibited rod-like structures. Specifically, Nano-IMI had average vertical and horizontal axis sizes of 239.5 nm and 561.8 nm, while Micro-IMI exhibited 6.7 µm and 22.1 µm, respectively. Compared to Micro-IMI, the small size effect of Nano-IMI affected the arrangement of interfacial molecules, reduced surface tension and contact angle, thereby improving the stability, dispersibility, foliar wettability, deposition and retention of the nano-system. Nano-IMI exhibited 1.3 times higher toxicity to Aphis gossypii Glover compared to Micro-IMI, attributed to its enhanced foliar utilization efficiency. Importantly, the Nano-IMI did not intensify the toxicity to non-target organism Apis mellifera L. This study systematically elucidates the influence of size effect on key indicators related to the effectiveness and safety, providing a theoretical basis for efficient and safe application of nanopesticides and critical insights into sustainable agriculture and environmental development.

Anterior percutaneous full-endoscopic transcorporeal decompression for cervical disc herniation: a finite element analysis and long-term follow-up study.

OBJECTIVE: The purpose of this study was to investigate the long-term consequences on the cervical spine after Anterior transcorporeal percutaneous endoscopy cervical discectomy (ATc-PECD) from the biomechanical standpoint. METHODS: A three-dimensional model of the normal cervical spine C2-T1 was established using finite element method. Subsequently, a disc degeneration model and degeneration with surgery model were constructed on the basis of the normal model. The same loading conditions were applied to simulate flexion, extension, lateral bending and axial rotation of the cervical spine. We calculated the cervical range of motion (ROM), intradiscal pressure, and intravertebral body pressure under different motions for observing changes in cervical spine biomechanics after surgery. At the same time, we combined the results of a long-term follow-up of the ATc-PECD, and used imaging methods to measure vertebral and disc height and cervical mobility, the Japanese Orthopaedic Association (JOA) score and visual analog scale (VAS) score were used to assess pain relief and neurological functional recovery. RESULTS: The long-term follow-up results revealed that preoperative JOA score, neck VAS score, hand VAS score, IDH, VBH, and ROM for patients were 9.49 ± 2.16, 6.34 ± 1.68, 5.14 ± 1.48, 5.95 ± 0.22 mm, 15.41 ± 1.68 mm, and 52.46 ± 9.36° respectively. It changed to 15.71 ± 1.13 (P < 0.05), 1.02 ± 0.82 (P < 0.05), 0.77 ± 0.76 (P < 0.05), 4.73 ± 0.26 mm (P < 0.05), 13.67 ± 1.48 mm (P < 0.05), and 59.26 ± 6.72° (P < 0.05), respectively, at 6 years postoperatively. Finite element analysis showed that after establishing the cervical spondylosis model, the overall motion range for flexion, extension, lateral bending, and rotation decreased by 3.298°, 0.753°, 3.852°, and 1.131° respectively. Conversely, after establishing the bone tunnel model, the motion range for these actions increased by 0.843°, 0.65°, 0.278°, and 0.488° respectively, consistent with the follow-up results. Moreover, analysis of segmental motion changes revealed that the increased cervical spine mobility was primarily contributed by the surgical model segments. Additionally, the finite element model demonstrated that bone tunneling could lead to increased stress within the vertebral bodies and intervertebral discs of the surgical segments. CONCLUSIONS: Long-term follow-up studies have shown that ATc-PECD has good clinical efficacy and that ATc-PECD can be used as a complementary method for CDH treatment. The FEM demonstrated that ATc-PECD can lead to increased internal stresses in the vertebral body and intervertebral discs of the operated segments, which is directly related to cervical spine degeneration after ATc-PECD.

Analysis of minimal levator ani hiatus area based on MRI in female adults without pelvic floor dysfunction at different age groups.

PURPOSE: To investigate the association of minimal levator ani hiatus area with age in female adults without pelvic floor dysfunction. METHODS: 532 female subjects aged 18 ~ 90 years without pelvic floor dysfunction, divided into four groups (Group A, 18 ~ 29 years old; Group B, 30 ~ 39 years old; Group C, 40 ~ 49 years old; Group D, ≥ 50 years old) based on age, underwent traditional pelvic two-dimensional (2D) T2-weighted imaging (T2WI) axial to the body (AxB) for measuring the minimal levator ani hiatus area. 39 female volunteers were re-recruited to undergo both traditional pelvic 2D T2WI AxB and three-dimensional (3D) T2WI. An axial plane parallel to the direction of the puborectalis muscle (AxPRM) was acquired based on 3D T2WI. The difference of levator ani hiatus area measured on AxB and AxPRM images in 39 female volunteers was compared by one-sample t test, to verify if minimal levator ani hiatus area can be acquired on the traditional pelvic 2D T2WI AxB images. Spearman analysis evaluated the association of minimal levator ani hiatus area with age and the rank-sum test analyzed the area differences among four age groups. RESULTS: Female age was positively correlated with minimal levator ani hiatus area (r = 0.23; p < 0.001). The minimal levator ani hiatus areas of 532 subjects were: 15.17 ± 1.77 cm2 in Group A, 15.52 ± 2.21 cm2 in Group B, 16.03 ± 2.16 cm2 in Group C, and 16.40 ± 2.10 cm2 in Group D. ANOVA showed significant statistical differences among four age groups (F = 7.519, p < 0.0001). Significant differences in minimal levator ani hiatus areas were found between Group A and Group C (p = 0.0491), Group A and Group D (p = 0.0007), and Group B and Group D (p < 0.001). There was no statistical difference in minimal levator ani hiatus areas measured on AxB and AxPRM images in 39 female volunteers (p = 0.1000). There were no statistical difference in minimal levator ani hiatus areas between nulliparous and multiparous group for each age group (all p > 0.05). CONCLUSIONS: Based on a large sample, this study summarized the minimum levator ani hiatus area of female adults without pelvic floor dysfunction in different age groups. We found significant differences among different age groups. In addition, a positive correlation was found between age and the minimum levator ani hiatus area. These findings can provide reference criteria for diagnosing pelvic organ prolapse in female adults of different age groups.

The key factors of solid nanodispersion for promoting the bioactivity of abamectin.

Solid nanodispersion (SND) is an important variety of nanopesticides which have been extensively studied in recent years. However, the key influencing factors for bioactivity enhancement of nanopesticides remain unclear, which not only limits the exploration of relevant mechanisms, but also hinders the precise design and development of nanopesticides. In this study, we explored the potential of SND in enhancing the bioactivity of nanopesticides, specifically focusing on abamectin SND prepared using a self-emulsifying-carrier solidifying technique combined with parameter optimization. Our formulation, consisting of 8% abamectin, 1% antioxidant BHT (2,6-di-tert-butyl-4-methylphenol), 12% complex surfactants, and 79% sodium benzoate, significantly increased the pseudo-solubility of abamectin by at least 3300 times and reduced its particle size to a mere 15 nm, much smaller than traditional emulsion in water (EW) and water-dispersible granule (WDG) forms. This reduction in particle size and increase in surface activity resulted in improved foliar adhesion and retention, enabling a more efficient application without the need for organic solvents. The inclusion of antioxidants also enhanced photostability compared to EW, and overall stability tests confirmed SND's resilience under various storage conditions. Bioactivity tests demonstrated a marked increase in toxicity against diamondback moths (Plutella xylostella L.) with abamectin SND, which exhibited 3.7 and 7.6 times greater efficacy compared to EW and WDG, respectively. These findings underscore the critical role of small particle size, high surface activity, and strong antioxidant properties in improving the performance and bioactivity of abamectin SND, highlighting its significance in the design and development of high-efficiency, eco-friendly nanopesticides and contributing valuably to sustainable agricultural practices.