TFAP2A is involved in neuropathic pain by regulating Grin1 expression in glial cells of the dorsal root ganglion.

Neuropathic pain is a highly prevalent and refractory condition, yet its mechanism remains poorly understood. While NR1, the essential subunit of NMDA receptors, has long been recognized for its pivotal role in nociceptive transmission, its involvement in presynaptic stimulation is incompletely elucidated. Transcription factors can regulate the expression of both pro-nociceptive and analgesic factors. Our study shows that transcription factor TFAP2A was up-regulated in the dorsal root ganglion (DRG) neurons, satellite glial cells (SGCs), and Schwann cells following spinal nerve ligation (SNL). Intrathecal injection of siRNA targeting Tfap2a immediately or 7 days after SNL effectively alleviated SNL-induced pain hypersensitivity and reduced Tfap2a expression levels. Bioinformatics analysis revealed that TFAP2A may regulate the expression of the Grin1 gene, which encodes NR1. Dual-luciferase reporter assays confirmed TFAP2A's positive regulation of Grin1 expression. Notably, both Tfap2a and Grin1 were expressed in the primary SGCs and upregulated by lipopolysaccharides. The expression of Grin1 was also down-regulated in the DRG following Tfap2a knockdown. Furthermore, intrathecal injection of siRNA targeting Grin1 immediately or 7 days post-SNL effectively alleviated SNL-induced mechanical allodynia and thermal hyperalgesia. Finally, intrathecal Tfap2a siRNA alleviated SNL-induced neuronal hypersensitivity, and incubation of primary SGCs with Tfap2a siRNA decreased NMDA-induced upregulation of proinflammatory cytokines. Collectively, our study reveals the role of TFAP2A-Grin1 in regulating neuropathic pain in peripheral glia, offering a new strategy for the development of novel analgesics.

Activation of pyramidal neurons in the infralimbic cortex alleviates LPS-induced depressive-like behavior in mice.

The infralimbic (IL) cortex dysfunction has been implicated in major depressive disorder (MDD), yet the precise cellular and molecular mechanisms remain poorly understood. In this study, we investigated the role of layer V pyramidal neurons in a mouse model of MDD induced by repeated lipopolysaccharide (LPS) administration. Our results demonstrate that three days of systemic LPS administration induced depressive-like behavior and upregulated mRNA levels of interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-ß (TGF-ß) in the IL cortex. Electrophysiological recordings revealed a significant decrease in the intrinsic excitability of layer V pyramidal neurons in the IL following systemic LPS exposure. Importantly, chemogenetic activation of IL pyramidal neurons ameliorated LPS-induced depressive-like behavior. Additionally, LPS administration significantly increased microglial activity in the IL, as evidenced by a greater number of Ionized calcium binding adaptor molecule-1 (IBA-1)-positive cells. Morphometric analysis further unveiled enlarged soma, decreased branch numbers, and shorter branch lengths of microglial cells in the IL cortex following LPS exposure. Moreover, the activation of pyramidal neurons by clozapine-N-oxide increased the microglia branch length but did not change branch number or cytosolic area. These results collectively suggest that targeted activation of pyramidal neurons in the IL cortex mitigates microglial response and ameliorates depressive-like behaviors induced by systemic LPS administration. Therefore, our findings offer potential therapeutic targets for the development of interventions aimed at alleviating depressive symptoms by modulating IL cortical circuitry and microglial activity.

Thermoregulatory pathway underlying the pyrogenic effects of prostaglandin E2 in the lateral parabrachial nucleus of male rats.

It has been shown that prostaglandin (PG) E2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE2 in male rats. The core temperature (Tcore) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE2. We demonstrated that EP3 receptor was a pivotal receptor for PGE2-induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE2, respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE2; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (IA) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE2; however, the IA current density was significantly increased by PGE2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of IA currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.

Pancreatic mucinous adenocarcinoma has different clinical characteristics and better prognosis compared to non-specific PDAC: A retrospective observational study.

Background: Pancreatic mucinous adenocarcinoma (PMAC) is a rare malignant tumour, and there is limited understanding of its epidemiology and prognosis. Initially, PMAC was considered a metastatic manifestation of other cancers; however, instances of non-metastatic PMAC have been documented through monitoring, epidemiological studies, and data from the Surveillance, Epidemiology, and End Results (SEER) database. Therefore, it is crucial to investigate the epidemiological characteristics of PMAC and discern the prognostic differences between PMAC and the more prevalent pancreatic ductal adenocarcinoma (PDAC). Methods: The study used data from the SEER database from 2000 to 2018 to identify patients diagnosed with PMAC or PDAC. To ensure comparable demographic characteristics between PDAC and PMAC, propensity score matching was employed. Kaplan-Meier analysis was used to analyse overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were used to determine independent risk factors influencing OS and CSS. Additionally, the construction and validation of risk-scoring models for OS and CSS were achieved through the least absolute shrinkage and selection operator-Cox regression technique. Results: The SEER database included 84,857 patients with PDAC and 3345 patients with PMAC. Notably, significant distinctions were observed in the distribution of tumour sites, diagnosis time, use of radiotherapy and chemotherapy, tumour size, grading, and staging between the two groups. The prognosis exhibited notable improvement among married individuals, those receiving acceptable chemotherapy, and those with focal PMAC (p < 0.05). Conversely, patients with elevated log odds of positive lymph node scores or higher pathological grades in the pancreatic tail exhibited a more unfavourable prognosis (p < 0.05). The risk-scoring models for OS or CSS based on prognostic factors indicated a significantly lower prognosis for high-risk patients compared to their low-risk counterparts (area under the curve OS: 0.81-0.82, CSS: 0.80-0.82). Conclusion: PMAC exhibits distinct clinical characteristics compared to non-specific PDAC. Leveraging these features and pathological classifications allows for accurate prognostication of PMAC or PDAC.

Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers: A case report and review of literature.

BACKGROUND: Genetic factors of chronic intestinal ulcers are increasingly garnering attention. We present a case of chronic intestinal ulcers and bleeding associated with mutations of the activin A receptor type II-like 1 (ACVRL1) and phospholipase A2 group IVA (PLA2G4A) genes and review the available relevant literature. CASE SUMMARY: A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain, diarrhea, and dark stools. At the onset 6 years ago, the patient had received treatment at a local hospital for abdominal pain persisting for 7 d, under the diagnosis of diffuse peritonitis, acute gangrenous appendicitis with perforation, adhesive intestinal obstruction, and pelvic abscess. The surgical treatment included exploratory laparotomy, appendectomy, intestinal adhesiolysis, and pelvic abscess removal. The patient's condition improved and he was discharged. However, the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge. On the basis of these features and results of subsequent colonoscopy, the clinical diagnosis was established as inflammatory bowel disease (IBD). Accordingly, aminosalicylic acid, immunotherapy, and related symptomatic treatment were administered, but the symptoms of the patient did not improve significantly. Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes. ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation, respectively. This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes. Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms. CONCLUSION: Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD. Orally administered Kangfuxin liquid may have therapeutic potential.

HFM-Tracker: a cell tracking algorithm based on hybrid feature matching.

Cell migration is known to be a fundamental biological process, playing an essential role in development, homeostasis, and diseases. This paper introduces a cell tracking algorithm named HFM-Tracker (Hybrid Feature Matching Tracker) that automatically identifies cell migration behaviours in consecutive images. It combines Contour Attention (CA) and Adaptive Confusion Matrix (ACM) modules to accurately capture cell contours in each image and track the dynamic behaviors of migrating cells in the field of view. Cells are firstly located and identified via the CA module-based cell detection network, and then associated and tracked via a cell tracking algorithm employing a hybrid feature-matching strategy. This proposed HFM-Tracker exhibits superiorities in cell detection and tracking, achieving 75% in MOTA (Multiple Object Tracking Accuracy) and 65% in IDF1 (ID F1 score). It provides quantitative analysis of the cell morphology and migration features, which could further help in understanding the complicated and diverse cell migration processes.

Cytochrome P450 26A1 Contributes to the Maintenance of Neuropathic Pain.

The cytochrome P450 proteins (CYP450s) have been implicated in catalyzing numerous important biological reactions and contribute to a variety of diseases. CYP26A1, a member of the CYP450 family, carries out the oxidative metabolism of retinoic acid (RA), the active metabolite of vitamin A. Here we report that CYP26A1 was dramatically upregulated in the spinal cord after spinal nerve ligation (SNL). CYP26A1 was mainly expressed in spinal neurons and astrocytes. HPLC analysis displayed that the content of all-trans-RA (at-RA), the substrate of CYP26A1, was reduced in the spinal cord on day 7 after SNL. Inhibition of CYP26A1 by siRNA or inhibition of CYP26A1-mediated at-RA catabolism by talarozole relieved the SNL-induced mechanical allodynia during the maintenance phase of neuropathic pain. Talarozole also reduced SNL-induced glial activation and proinflammatory cytokine production but increased anti-inflammatory cytokine (IL-10) production. The RA receptors RARα, RXRß, and RXRγ were expressed in spinal neurons and glial cells. The promoter of Il-10 has several binding sites for RA receptors, and at-RA directly increased Il-10 mRNA expression in vitro. Finally, intrathecal IL-10 attenuated SNL-induced neuropathic pain and reduced the activation of astrocytes and microglia. Collectively, the inhibition of CYP26A1-mediated at-RA catabolism alleviates SNL-induced neuropathic pain by promoting the expression of IL-10 and suppressing glial activation. CYP26A1 may be a potential therapeutic target for the treatment of neuropathic pain.

Identification of miRNA858 long-loop precursors in seed plants.

MicroRNAs (miRNAs) are a class of nonprotein-coding short transcripts that provide a layer of post-transcriptional regulation essential to many plant biological processes. MiR858, which targets the transcripts of MYB transcription factors, can affect a range of secondary metabolic processes. Although miR858 and its 187-nt precursor have been well studied in Arabidopsis (Arabidopsis thaliana), a systematic investigation of miR858 precursors and their functions across plant species is lacking due to a problem in identifying the transcripts that generate this subclass. By re-evaluating the transcript of miR858 and relaxing the length cut-off for identifying hairpins, we found in kiwifruit (Actinidia chinensis) that miR858 has long-loop hairpins (1,100 to 2,100 nt), whose intervening sequences between miRNA generating complementary sites were longer than all previously reported miRNA hairpins. Importantly, these precursors of miR858 containing long-loop hairpins (termed MIR858L) are widespread in seed plants including Arabidopsis, varying between 350 and 5,500 nt. Moreover, we showed that MIR858L has a greater impact on proanthocyanidin and flavonol levels in both Arabidopsis and kiwifruit. We suggest that an active MIR858L-MYB regulatory module appeared in the transition of early land plants to large upright flowering plants, making a key contribution to plant secondary metabolism.

Spatial distribution, source identification, and transportation paths of plutonium in the Beibu Gulf, South China Sea.

To investigate the spatial distribution and source of plutonium isotopes in the Beibu Gulf, surface sediments were collected and analyzed using sector field inductively coupled plasma mass spectrometry (SF-ICP-MS). The activities of 239+240Pu in surface sediments ranged from 0.012 to 0.451 mBq/g (mean: 0.171 ± 0.138 mBq/g, n = 36), indicating a decreasing trend in a counterclockwise direction from the southern bay mouth. The counterclockwise decreasing trend in the south of the bay mouth is similar to the current in the Beibu Gulf. The 240Pu/239Pu atom ratios in surface sediments ranged from 0.156 to 0.283 (mean: 0.236 ± 0.031, n = 36), slightly higher than that of the global fallout value of 0.18. This suggests that the Pu in the Beibu Gulf was a combination of global fallout and Pacific Proving Ground (PPG). The average contribution of the plutonium (Pu) derived from the PPG in the sediment was estimated to be 52 % ± 24 %.

Optimal timing for early mobilization initiatives in intensive care unit patients: A systematic review and network meta-analysis.

OBJECTIVES: Analyse the effect of varying start times for early exercise interventions on the prevention of intensive care unit-acquired weakness. RESEARCH METHODOLOGY: We conducted a comprehensive search on PubMed, Cochrane Library, Web of Science, Embase, China Biology Medicine Disc, China National Knowledge Infrastructure, Wan Fang Database, and reference lists up to May 2023. SETTING: We systematically searched the literature for all randomized controlled trials on the effect of early mobilization in patients with critical illness. MAIN OUTCOME MEASURES: The primary outcome assessed was the incidence of intensive care unit-acquired weakness. The secondary outcomes included: the Medical Research Council Score, the Barthel Index, duration of mechanical ventilation, length of intensive care unit stay, total length of hospital stay, mortality and incidence of intensive care unit-related complications. RESULTS: The results of meta-analysis showed that compared with routine care, less than 24 hours after admission (RR = 0.44, 95 %CI: 0.28-0.68), more than 24 hours (RR = 0.33, 95 %CI: 0.16-0.67), less than 72 hours after admission (RR = 0.33, 95 %CI: 0.20-0.52) may lead to a lower incidence of intensive care unit-acquired weakness. The results of under surface cumulative ranking showed that early mobilization within 72 hours may have the lowest incidence of intensive care unit-acquired weakness (SUCRA = 81.9 %). CONCLUSIONS: The current empirical evidence from intensive care unit patients suggests that initiating mobilization protocols within 24-72 hours timeframe following admission to the intensive care unit could potentially be the most beneficial strategy to reduce the incidence of intensive care unit-acquired weakness and the related medical complications. Moreover, this strategy seems to significantly improve rehabilitation and treatment outcomes for these patients. IMPLICATIONS FOR CLINICAL PRACTICE: According to this study, medical and nursing staff in the intensive care unit have the chance to identify the most suitable timing for the implementation of early rehabilitative measures for patients. This can potentially prevent intensive care unit-acquired weakness and enhance various clinical outcomes for patients.

Benthic primary production decreases internal phosphorus loading from lake sediments under light supplement.

In aquatic ecosystems, light penetrating the sediment surface in shallow lakes may regulate the internal phosphorus (P) release through benthic primary production, which subsequently affects oxidation, pH levels, and alkaline phosphatase activity in the upper sediment. To study the effects of light exposure on the P dynamics at the sediment-water interface under eutrophic conditions, a two-month mesocosm experiment was conducted in twelve cement tanks (1000 L each). The tanks were equipped with Light-Emitting Diode (LED) lights, and surface sediments collected from eutrophic Lake Nanhu (China) were exposed to four different light intensities (0, 50, 100, 200 µmol m-2 s-1). The results revealed that: 1) Both the total phosphorus concentration and the phosphorus release flux from the sediment were lower in the light treatments (mean value, 0.59-0.71 mg L-1 and 0.00-0.01 mg m-2 d-1, respectively) than in the control treatment (0.77 mg L-1 and 0.01 mg m-2 d-1, respectively), indicating that light supplement could decrease the internal P release. 2) Benthic primary production promoted by light directly absorbed soluble reactive phosphorus and decreased the internal P release. The resulting improved production could also increase dissolved oxygen concentrations at the sediment-water interface, thus indirectly inhibiting internal P release. 3) The relative contributions of direct absorption and indirect inhibition on the internal P release ranged between 23% to 69% and 31% to 77% depending on the light intensity.

A nomogram for the prediction of survival for colorectal signet ring cell carcinoma after surgery: A population-based study.

The aim was to construct and verify a nomogram-based assessment of cancer-specific survival (CSS) in patients with colorectal signet ring cell carcinoma after surgery. Patients were collected from Surveillance, Epidemiology, and End Results program between 2004 and 2015. Independent prognostic indicators were determined in the training cohort by Cox regression model. We identified 2217 eligible patients, who were further categorized into the training set (n = 1693) as well as the validation set (n = 524). Multivariate analysis revealed that age at diagnosis, gender, grade, tumor size, T stage, N stage, and M stage were independent predictive indicators. Then, the above 7 predictive factors were incorporated into a nomogram model to assess CSS, which showed good calibration and discrimination capacities in both sets. Both internal and external calibration plot diagrams revealed that the actual results were consistent with the predicted outcomes. The time-independent area under the curves for 3-year and 5-year CSS in the nomogram were larger than American Joint Committee on Cancer and Surveillance, Epidemiology, and End Results summary stage system. Moreover, decision curve analysis indicated the clinical utility of the nomogram. The nomogram demonstrated favorable predictive accuracy of survival in colorectal signet ring cell carcinoma patients after surgery, which should be further confirmed before clinical implementation.

[A case of duodenal ulcer as prominent manifestation of IgG4-related disease].

A case of IgG4-related disease presented with a duodenal ulcer to improve the understan-ding of IgG4-related diseases was reported. A 70-year-old male presented with cutaneous pruritus and abdominal pain for four years and blackened stools for two months. Four years ago, the patient went to hospital for cutaneous pruritus and abdominal pain. Serum IgG4 was 3.09 g/L (reference value 0-1.35 g/L), alanine aminotransferase 554 U/L (reference value 9-40 U/L), aspartate aminotransferase 288 U/L (reference value 5-40 U/L), total bilirubin 54.16 µmol/L (reference value 2-21 µmol/L), and direct bilirubin 29.64 µmol/L (reference value 1.7-8.1 µmol/L) were all elevated. The abdominal CT scan and magnetic resonance cholangiopancreatography indicated pancreatic swelling, common bile duct stenosis, and secondary obstructive dilation of the biliary system. The patient was diagnosed with IgG4-related disease and treated with prednisone at 40 mg daily. As jaundice and abdominal pain improved, prednisone was gradually reduced to medication discontinuation. Two months ago, the patient developed melena, whose blood routine test showed severe anemia, and gastrointestinal bleeding was diagnosed. The patient came to the emergency department of Beijing Hospital with no improvement after treatment in other hospitals. Gastroscopy revealed a 1.5 cm firm duodenal bulb ulcer. After treatment with omeprazole, the fecal occult blood was still positive. The PET-CT examination was performed, and it revealed no abnormality in the metabolic activity of the duodenal wall, and no neoplastic lesions were found. IgG4-related disease was considered, and the patient was admitted to the Department of Rheumatology and Immunology of Beijing Hospital for further diagnosis and treatment. The patient had a right submandibular gland mass resection history and diabetes mellitus. After the patient was admitted to the hospital, the blood test was reevaluated. The serum IgG4 was elevated at 5.44 g/L (reference value 0.03-2.01 g/L). Enhanced CT of the abdomen showed that the pancreas was mild swelling and was abnormally strengthened, with intrahepatic and extrahepatic bile duct dilation and soft tissue around the superior mesenteric vessels. We pathologically reevaluated and stained biopsy specimens of duodenal bulbs for IgG and IgG4. Immunohistochemical staining revealed remarkable infiltration of IgG4-positive plasma cells into duodenal tissue, the number of IgG4-positive cells was 20-30 cells per high-powered field, and the ratio of IgG4/IgG-positive plasma cells was more than 40%. The patient was treated with intravenous methylprednisolone at 40 mg daily dosage and cyclophosphamide, and then the duodenal ulcer was healed. IgG4 related disease is an immune-medicated rare disease characterized by chronic inflammation and fibrosis. It is a systemic disease that affects nearly every anatomic site of the body, usually involving multiple organs and diverse clinical manifestations. The digestive system manifestations of IgG4-related disease are mostly acute pancreatitis and cholangitis and rarely manifest as gastrointestinal ulcers. This case confirms that IgG4-related disease can present as a duodenal ulcer and is one of the rare causes of duodenal ulcers.

Development and validation of a nomogram to predict overall survival for cervical adenocarcinoma: A population-based study.

This study aimed to develop and validate a nomogram for predicting the overall survival of cervical adenocarcinoma (CAC) patients using a large database comprising patients with different ethnicities. We enrolled primary CAC cases with complete clinicopathological and survival data from the Surveillance, Epidemiology, and End Results program during 2004 to 2015. For training set samples, this work applied the Cox regression model to obtain factors independently associated with patient prognosis, which could be incorporated in constructing the nomogram. Altogether 3096 qualified cases were enrolled, their survival ranged from 0 to 155 (median, 45.5) months. As revealed by multivariate regression, age, marital status, tumor size, grade, International Federation of Gynecology and Obstetrics (FIGO) classification, pelvic lymph node metastasis, surgery, and chemotherapy served as the factors to independently predict CAC (all P < .05). We later incorporated these factors for constructing the nomogram. According to the concordance index determined, this nomogram had superior discrimination over FIGO classification system (all P < .001). Based on calibration plot, the predicted value was consistent with actual measurement. As revealed by time-independent area under the curves, our constructed nomogram had superior 5-year overall survival over FIGO system. Additionally, according to decision curve analysis, our constructed nomogram showed high clinical usefulness as well as favorable discrimination. Our constructed nomogram attains favorable performances, indicating that it may be applied in predicting survival for CAC patients.

Treponema pallidum Promotes the Polarization of M2 Subtype Macrophages to M1 Subtype Mediating the Apoptosis and Inhibiting the Angiogenesis of Human Umbilical Vein Endothelial Cells.

M2 macrophages were related to local immune homeostasis and maternal-fetal tolerance in normal pregnancy; whether M2 macrophages can respond to the stimulation of Treponema pallidum to mediate placental vascular inflammation injury is unclear. In this study, M2 macrophages were constructed to investigate the impact of T. pallidum on macrophage polarization and the underlying signaling pathway involved in this process, and the influence of macrophage polarization triggered by T. pallidum on the apoptosis and angiogenesis of human umbilical vein endothelial cells (HUVEC) was also explored. The results showed that M2 macrophage markers (CD206 and PPARγ) and anti-inflammatory factors (TGFß and CCL18) were decreased, while M1 macrophage marker CD80 and inflammatory cytokines (IL1ß and TNFα) were increased when M2 macrophages were treated with T. pallidum, indicating that T. pallidum promoted the polarization of M2 subtype macrophages to the M1 subtype. Moreover, T. pallidum-induced M1 macrophage polarization was found to be significantly correlated with the activation of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 1 (STAT1). In addition, T. pallidum-induced M1 macrophages were found to promote apoptosis and inhibit the angiogenesis of HUVECs, and JAK1 or STAT1 inhibitors could weaken the apoptosis rate and promote the angiogenesis of HUVECs. These findings revealed that T. pallidum promoted the polarization of M2 macrophages to the M1 subtype through the JAK1-STAT1 signal pathway mediating the apoptosis and inhibiting angiogenesis of HUVECs, which may provide a possible mechanism for T. pallidum-induced adverse pregnancy outcomes.

Targeting TRIP13 for overcoming anticancer drug resistance (Review).

Cancer is one of the greatest dangers to human wellbeing and survival. A key barrier to effective cancer therapy is development of resistance to anti­cancer medications. In cancer cells, the AAA+ ATPase family member thyroid hormone receptor interactor 13 (TRIP13) is key in promoting treatment resistance. Nonetheless, knowledge of the molecular processes underlying TRIP13­based resistance to anticancer therapies is lacking. The present study evaluated the function of TRIP13 expression in anticancer drug resistance and potential methods to overcome this resistance. Additionally, the underlying mechanisms by which TRIP13 promotes resistance to anticancer drugs were explored, including induction of mitotic checkpoint complex surveillance system malfunction, promotion of DNA repair, the enhancement of autophagy and the prevention of immunological clearance. The effects of combination treatment, which include a TRIP13 inhibitor in addition to other inhibitors, were discussed. The present study evaluated the literature on TRIP13 as a possible target and its association with anticancer drug resistance, which may facilitate improvements in current anticancer therapeutic options.

Cloning and functional study of GmRPI2, which is the critical gene of photosynthesis in soybean.

Light provides energy for photosynthesis and is also an important environmental signal that regulates plant growth and development. Ribose-5-phosphate isomerase plays a crucial role in photosynthesis. However, ribose-5-phosphate isomerase has yet to be studied in soybean photosynthesis. To understand the biological function of GmRPI2, in this study, GmRPI2 was cloned, plant overexpression vectors and gene editing vectors were successfully constructed, and transformed into recipient soybean JN74 using the Agrobacterium-mediated method. Using qRT-PCR, we analyzed that GmRPI2 gene expression was highest in leaves, second highest in roots, and lowest in stems. Promoter analysis revealed the presence of multiple cis-acting elements related to light response in the promoter region of GmRPI2. Compared with the control soybean plants, the net photosynthetic rate and transpiration rate of the overexpression lines were higher than those of the control and gene editing lines, while the intercellular CO2 concentration was significantly lower than that of the control and gene editing lines; the total chlorophyll, chlorophyll a, chlorophyll b contents and soluble sugar contents of the overexpression plants were significantly higher than those of the recipient and editing plants, indicating that the GmRPI2 gene can increase The GmRPI2 gene can increase the photosynthetic capacity of soybean plants, providing a theoretical basis and genetic resources for improving soybean yield by regulating photosynthetic efficiency.

Insights into the protective immune response by immunization with full-length recombinant TprK protein: cellular and humoral responses.

Syphilis has resurged in many countries, which has called attention to vaccine development. Based on the immunization-based rabbit model of infection with the Nichols strain, this study explored the protective immune response of a controversial syphilis vaccine candidate, TprK, and found that immunization with full-length rTprK was effective in attenuating lesion development and accelerating lesion resolution, which could reduce the probability of the pathogen spreading to distant tissue sites to prevent the progression of the disease to some extent. Furthermore, the results revealed that immunization with rTprK not only rapidly induced a strong Th1-like cellular response but also elicited a humoral immune response to produce opsonic antibodies to enhance macrophage-mediated opsonophagocytosis. Although complete protection against infection was not achieved, the study provided a comprehensive and in-depth exploration of the immunogenicity of TprK and highlighted the importance of TprK as a promising syphilis vaccine component.

Ultrasonic extraction and purification of scutellarin from Erigerontis Herba using deep eutectic solvent.

Nowadays, deep eutectic solvent (DES) was widely used in the extraction of bioactive in traditional Chinese medicine (TCM) as an alternative to organic solvents. While as, it is still a challenge for the removal of DES solvents and recovery of the extracted product. In this study, a simple, efficient and green technique of preparing scutellarin from Erigerontis Herba(EH) was proposed, combining ultrasonic assisted-DES extraction with anti-solvent purification. Firstly, different types of DES were prepared and studied for their abilities to extract scutellarin from EH. DES composed of choline chloride and acetamide (1:4 mol/mol) with 30% water obtained the highest extraction yield. Anti-solvent was proved as an efficient method to recover scutellarin from the DES extract with a content of purification up to 71.2%. Moreover, microscopic structural analysis was carried out to investigate the extract process and explain the extraction principle. Furthermore, the antioxidative activities of the DES extracts were evaluated, indicated that the bioactive property of scutellarin were still remained by using DES as the extraction solvent. In conclusion, the proposed simple and green ultrasonic assisted DES extraction method will serve as an effective alternative strategy to extract bioactive compounds from TCM.

Descending dopaminergic pathway facilitates itch signal processing via activating spinal GRPR+ neurons.

A11 dopaminergic neurons regulate somatosensory transduction by projecting from the diencephalon to the spinal cord, but the function of this descending projection in itch remained elusive. Here, we report that dopaminergic projection neurons from the A11 nucleus to the spinal dorsal horn (dopaminergicA11-SDH ) are activated by pruritogens. Inhibition of these neurons alleviates itch-induced scratching behaviors. Furthermore, chemogenetic inhibition of spinal dopamine receptor D1-expressing (DRD1+ ) neurons decreases acute or chronic itch-induced scratching. Mechanistically, spinal DRD1+ neurons are excitatory and mostly co-localize with gastrin-releasing peptide (GRP), an endogenous neuropeptide for itch. In addition, DRD1+ neurons form synapses with GRP receptor-expressing (GRPR+ ) neurons and activate these neurons via AMPA receptor (AMPAR). Finally, spontaneous itch and enhanced acute itch induced by activating spinal DRD1+ neurons are relieved by antagonists against AMPAR and GRPR. Thus, the descending dopaminergic pathway facilitates spinal itch transmission via activating DRD1+ neurons and releasing glutamate and GRP, which directly augments GRPR signaling. Interruption of this descending pathway may be used to treat chronic itch.