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.

Reversible Switching Between Microwave Absorption and EMI Shielding of VO2 Composite Foam.

Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO2/EPM) is designed and fabricated with porous structures and 3D VO2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO2/EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO2. Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO2/EPM before and after the phase transition. Moreover, the application of VO2/EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices.

Peripheral inflammation triggering central anxiety through the hippocampal glutamate metabolized receptor 1.

AIMS: This study aimed to investigate the relationship between ulcerative colitis (UC) and anxiety and explore its central mechanisms using colitis mice. METHODS: Anxiety-like behavior was assessed in mice induced by 3% dextran sodium sulfate (DSS) using the elevated plus maze and open-field test. The spatial transcriptome of the hippocampus was analyzed to assess the distribution of excitatory and inhibitory synapses, and Toll-like receptor 4 (TLR4) inhibitor TAK-242 (10 mg/kg) and AAV virus interference were used to examine the role of peripheral inflammation and central molecules such as Glutamate Receptor Metabotropic 1 (GRM1) in mediating anxiety behavior in colitis mice. RESULTS: DSS-induced colitis increased anxiety-like behaviors, which was reduced by TAK-242. Spatial transcriptome analysis of the hippocampus showed an excitatory-inhibitory imbalance mediated by glutamatergic synapses, and GRM1 in hippocampus was identified as a critical mediator of anxiety behavior in colitis mice via differential gene screening and AAV virus interference. CONCLUSION: Our work suggests that the hippocampus plays an important role in brain anxiety caused by peripheral inflammation, and over-excitation of hippocampal glutamate synapses by GRM1 activation induces anxiety-like behavior in colitis mice. These findings provide new insights into the central mechanisms underlying anxiety in UC and may contribute to the development of novel therapeutic strategies for UC-associated anxiety.

Metabolomic and transcriptomic reveal flavonoid biosynthesis and regulation mechanism in Phlomoides rotata from different habitats.

Phlomoides rotata is a traditional medical plant at 3100-5200 m altitude in the Tibet Plateau. In this study, flavonoid metabolites were investigated in P. rotata from Henan County (HN), Guoluo County (GL), Yushu County (YS), and Chengduo County (CD) habitats in Qinghai. The level of kaempferol 3-neohesperidoside, sakuranetin, and biochanin A was high in HN. The content of limocitrin and isoquercetin was high in YS. The levels of ikarisoside A and chrysosplenol D in GL were high. Schaftoside, miquelianin, malvidin chloride, and glabrene in CD exhibited high levels. The results showed a significant correlation between 59 flavonoids and 29 DEGs. Eleven flavonoids increased with altitude. PAL2, UFGT6, COMT1, HCT2, 4CL4, and HCT3 genes were crucial in regulating flavonoid biosynthesis. Three enzymes CHS, 4CL, and UFGT, were crucial in regulating flavonoid biosynthesis. This study provided biological and chemical evidence for the different uses of various regional plants of P. rotata.

Hypoxia-induced miR-5100 promotes exosome-mediated activation of cancer-associated fibroblasts and metastasis of head and neck squamous cell carcinoma.

The invasion-metastasis cascade in head and neck squamous cell carcinoma (HNSCC) is predominantly caused by the interaction between tumor cells and tumor microenvironment, including hypoxia as well as stromal cells. However, the mechanism of hypoxia-activated tumor-stroma crosstalk in HNSCC metastasis remains to be deciphered. Here, we demonstrated that HIF1α was upregulated in HNSCC specimens compared with adjacent normal tissues, whose overexpression was associated with lymph node metastasis and predicted unfavorable prognosis. HIF1α expression correlated positively with the levels of miR-5100 as well as α-SMA, the marker of CAFs. Hypoxia/HIF1α regulated transcriptionally miR-5100 to promote the degradation of its target gene QKI, which acts as a tumor suppressor in HNSCC. Hypoxic HNSCC-derived exosomal miR-5100 promoted the activation of CAFs by orchestrating QKI/AKT/STAT3 axis, which further facilitated HNSCC metastasis. Additionally, miR-5100 derived from plasma exosomes indicated HNSCC malignant progression. In conclusion, our findings illuminate a novel HIF1α/miR-5100/QKI pathway in HNSCC metastasis, and suggest that miR-5100 might be a potential biomarker and therapeutic target for HNSCC.

Coordination of histone chaperones for parental histone segregation and epigenetic inheritance.

Chromatin-based epigenetic memory relies on the accurate distribution of parental histone H3-H4 tetramers to newly replicated DNA strands. Mcm2, a subunit of the replicative helicase, and Dpb3/4, subunits of DNA polymerase ε, govern parental histone H3-H4 deposition to the lagging and leading strands, respectively. However, their contribution to epigenetic inheritance remains controversial. Here, using fission yeast heterochromatin inheritance systems that eliminate interference from initiation pathways, we show that a Mcm2 histone binding mutation severely disrupts heterochromatin inheritance, while mutations in Dpb3/4 cause only moderate defects. Surprisingly, simultaneous mutations of Mcm2 and Dpb3/4 stabilize heterochromatin inheritance. eSPAN (enrichment and sequencing of protein-associated nascent DNA) analyses confirmed the conservation of Mcm2 and Dpb3/4 functions in parental histone H3-H4 segregation, with their combined absence showing a more symmetric distribution of parental histone H3-H4 than either single mutation alone. Furthermore, the FACT histone chaperone regulates parental histone transfer to both strands and collaborates with Mcm2 and Dpb3/4 to maintain parental histone H3-H4 density and faithful heterochromatin inheritance. These results underscore the importance of both symmetric distribution of parental histones and their density at daughter strands for epigenetic inheritance and unveil distinctive properties of parental histone chaperones during DNA replication.

Enhancing the Interaction of Carbon Nanotubes by Metal-Organic Decomposition with Improved Mechanical Strength and Ultra-Broadband EMI Shielding Performance.

The remarkable properties of carbon nanotubes (CNTs) have led to promising applications in the field of electromagnetic interference (EMI) shielding. However, for macroscopic CNT assemblies, such as CNT film, achieving high electrical and mechanical properties remains challenging, which heavily depends on the tube-tube interactions of CNTs. Herein, we develop a novel strategy based on metal-organic decomposition (MOD) to fabricate a flexible silver-carbon nanotube (Ag-CNT) film. The Ag particles are introduced in situ into the CNT film through annealing of MOD, leading to enhanced tube-tube interactions. As a result, the electrical conductivity of Ag-CNT film is up to 6.82 × 105 S m-1, and the EMI shielding effectiveness of Ag-CNT film with a thickness of ~ 7.8 µm exceeds 66 dB in the ultra-broad frequency range (3-40 GHz). The tensile strength and Young's modulus of Ag-CNT film increase from 30.09 ± 3.14 to 76.06 ± 6.20 MPa (~ 253%) and from 1.12 ± 0.33 to 8.90 ± 0.97 GPa (~ 795%), respectively. Moreover, the Ag-CNT film exhibits excellent near-field shielding performance, which can effectively block wireless transmission. This innovative approach provides an effective route to further apply macroscopic CNT assemblies to future portable and wearable electronic devices.

Association Between Number of Missing Teeth and Hyperlipidemia: The TCLSIH Cohort Study.

Background: To explore the association between the number of missing teeth and the prevalence of hyperlipidemia in a Chinese adult population. Methods: 13,932 adults were investigated in the TCLSIH cohort study. The number of missing teeth was determined at baseline through a self-reported questionnaire, and then classified into three categories: 0, 1-2, and ≥3. We defined hyperlipidemia as total cholesterol (TC) ≥ 5.17 mmol/L or triglycerides (TG) ≥ 1.7 mmol/L or low-density lipoprotein (LDL) cholesterol ≥ 3.37 mmol/L or a self-report of physician-diagnosed hyperlipidemia during follow-up visits. Cox proportional-hazards regression models were employed to assess the relationship between the number of missing teeth and incident hyperlipidemia. Results: A total of 6756 first-incident cases of hyperlipidemia occurred during 42,048 person-years of follow-up (median follow-up, 4.2 years). After adjusted confounders, multivariable HRs and 95% CI for incident of hyperlipidemia across the categories of missing teeth were as follows: in male participants, 1.00 (reference), 1.10 (0.98, 1.22), and 1.03 (0.91, 1.16) (P for trend = 0.30); in female participants, 1.00 (reference), 1.09 (0.99, 1.19), and 1.18 (1.04, 1.33) (P for trend < 0.01). Conclusion: The number of missing teeth is associated with an increased risk of hyperlipidemia in female participants but not in male participants. Systemic chronic inflammation may potentially mediate this association.

Effects of moxibustion on visceral hypersensitivity and colonic inflammatory response in mice with chronic ulcerative colitis. / è‰¾ç¸å¯¹æ ¢æ€§æºƒç–¡æ€§ç»“è‚ ç‚Žå°é¼ å† è„é«˜æ•åŠç»“è‚ ç»„ç»‡ç‚Žæ€§ååº”çš„å½±å“.

OBJECTIVES: To observe the effects of moxibustion at "Zusanli" (ST36) on the expression levels of tumor necrosis factor (TNF)-α, TNF receptor 1 (TNF-R1), p38 mitogen-activated protein kinase (P38 MAPK), and transient receptor potential vanilloid 1 (TRPV1) in the colon tissue of mice with chronic ulcerative colitis (UC), so as to explore the underlying mechanisms of moxibustion in improving visceral hypersensitivity in chronic UC. METHODS: Male C57BL/6J mice were randomly divided into normal group, normal with moxibustion (NM) group, model group, and model with moxibustion (MM) group, with 10 mice in each group. The chronic UC model was established by drinking 2.5% dextran sodium sulfate for 3 cycles. Mice in the NM and MM groups received moxibustion at ST36 for 20 min, 5 days per week with a 2-day break, for a total of 4 weeks. The disease activity index (DAI) score of each group was evaluated before and after treatment. The minimum volume threshold of abdominal wall retraction reflex (AWR) was measured to observe the intestinal sensitivity of mice. The colon length was measured. The pathological changes of colon tissue were observed by HE staining. The expression of mucin in colon goblet cells was detected by periodate Scheff staining. The intestinal fibrosis was observed by Masson staining. The number of trypsin-positive cells (i.e., mast cell) and the expression level of TNF-α in colon tissue were detected by immunofluorescence staining. The expression levels of TNF-R1, P38 MAPK and TRPV1 in colon tissue were detected by immunohistochemistry. RESULTS: Compared with the normal group after treatment, the model group showed increased DAI score (P<0.001), decreased AWR minimum volume threshold (P<0.01), shortened colon length (P<0.001), significant inflammatory infiltration in the colon tissue, reduced mucin secretion (P<0.01), increased collagen fiber deposition (P<0.001), and elevated expression levels of TNF-α, TNF-R1, P38 MAPK, and TRPV1 (P<0.001, P<0.01, P<0.05). Compared with the model group, the MM group showed decreased DAI score (P<0.01), increased AWR minimum volume threshold (P<0.001), elongated colon length (P<0.001), reduced inflammatory cell infiltration, improved integrity of mucosal glandular structure, enhanced mucin secretion (P<0.01), decreased collagen fiber deposition (P<0.001), decreased number of mast cells in the colon tissue (P<0.001), and decreased expression levels of TNF-α, TNF-R1, P38 MAPK, and TRPV1 (P<0.001, P<0.01, P<0.05). There were no significant differences in the above index between the NM group and the normal group. CONCLUSIONS: Moxibustion can reduce visceral hypersensitivity, alleviate inflammatory infiltration and fibrotic damage in the colon tissue of mice with chronic UC. These effects may be associated with the down-regulation of TNF-α, TNF-R1, P38 MAPK, and TRPV1 expression in colon.

Surgical excision of a giant solitary keratoacanthoma in the cheek: a case report and literature review.

Background: Giant keratoacanthoma, a rare variant solitary of keratoacanthoma is characterized by a diameter exceeding 20 mm, rapid growth, and destruction of underlying tissue. Traditionally, it has been considered to be a self-resolving or low-grade squamous proliferation. Due to their atypical appearance, Giant keratoacanthomas may present a diagnostic challenge. Histopathological examination remains the reference standard for distinguishing squamous cell carcinoma (SCC) from keratoacanthoma. Surgical management is still the standard treatment for solitary keratoacanthoma. Case Description: We present the case of a 75-year-old man with a giant keratoacanthoma of the cheek, with a transverse length of 25 mm and a longitudinal length of 30 mm located 30 mm below the earlobe that was surgically excised with no obvious recurrence during follow-up. We used the Intraoperative frozen-section examination, which played a crucial role in ensuring clear margins and complete tumor removal. Conclusions: This case demonstrates that keratoacanthoma can be considered surgically curable and should be distinguished from SCC and other crateriform tumors. After surgical resection of giant isolated keratoacanthoma on the face, the high risk of cosmetic problems should be considered. We suggest free-flap transplantation be performed for functional repair, when the invasion range of the tumor is large and a perforation defect is formed.

Children with severe neurological symptoms associated with SARS-CoV-2 infection during Omicron pandemic in China.

BACKGROUND: To analyze the clinical characteristics and outcomes of children with severe neurological symptoms associated with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the Omicron pandemic in China. METHODS: This study used a questionnaire to obtain data from pediatric intensive care unit (PICU) centers in seven tertiary hospitals in Northeast China from December 1, 2022, to January 31, 2023. RESULTS: A total of 255 patients were confirmed to have SARS-CoV-2 infection, and 45 patients (17.65 %) were included in this study. Of these, seven (15.6%) patients died, and the median time from admission to death was 35 h (IQR, 14-120 h). Twenty (52.6%) survivors experienced neurological sequelae. Patients with platelet counts lower than 100 × 109/L had a higher incidence of complications such as multiple organ dysfunction, mechanical ventilation rate, and mortality. Cranial magnetic resonance imaging (MRI) always reveals cerebral tissue edema, with some severe lesions forming a softening site. CONCLUSION: Children infected with SARS-CoV-2 often exhibit severe neurological symptoms, and in some cases, they may rapidly develop malignant cerebral edema or herniation, leading to a fatal outcome. An early decrease in platelet count may associated with an unfavorable prognosis. IMPACT: Since early December 2022, China has gradually adjusted its prevention and control policy of SARS-CoV-2; Omicron outbreaks have occurred in some areas for a relatively short period. Due to the differences in ethnicity, endemic strains and vaccination status, there was a little difference from what has been reported about children with SARS-CoV-2 infection with severe neurological symptoms in abroad. This is the first multicenter clinical study in children with nervous system involvement after acute SARS-CoV-2 infection in China, and helpful for pediatricians to have a more comprehensive understanding of the clinical symptoms and prognosis of such disease.

The anticancer compound JTE-607 reveals hidden sequence specificity of the mRNA 3' processing machinery.

JTE-607 is an anticancer and anti-inflammatory compound and its active form, compound 2, directly binds to and inhibits CPSF73, the endonuclease for the cleavage step in pre-messenger RNA (pre-mRNA) 3' processing. Surprisingly, compound 2-mediated inhibition of pre-mRNA cleavage is sequence specific and the drug sensitivity is predominantly determined by sequences flanking the cleavage site (CS). Using massively parallel in vitro assays, we identified key sequence features that determine drug sensitivity. We trained a machine learning model that can predict poly(A) site (PAS) relative sensitivity to compound 2 and provide the molecular basis for understanding the impact of JTE-607 on PAS selection and transcription termination genome wide. We propose that CPSF73 and associated factors bind to the CS region in a sequence-dependent manner and the interaction affinity determines compound 2 sensitivity. These results have not only elucidated the mechanism of action of JTE-607, but also unveiled an evolutionarily conserved sequence specificity of the mRNA 3' processing machinery.

Moxibustion influences hippocampal microglia polarization via IL-33/ST2 pathway in Alzheimer's disease mice. / è‰¾ç¸é€šè¿‡ç™½ç»†èƒžä»‹ç´ -33/ç”Ÿé•¿åˆºæ¿€è¡¨è¾¾åŸºå› 2è›‹ç™½é€šè·¯å½±å“é˜¿å°”èŒ¨æµ·é»˜ç— å°é¼ æµ·é©¬å°èƒ¶è´¨ç»†èƒžæžåŒ–.

OBJECTIVES: To observe the effect of moxibustion on the polarization of microglia towards M2 direction in Alzheimer's disease (AD) mice through the interleukin-33 (IL-33)/growth stimulating gene 2 protein (ST2) signaling pathway. METHODS: Five-month-old APP/PS1 male mice were randomly divided into model and moxibustion (Moxi) groups, and C57BL/6J mice of the same age were as the control group, with 9 mice in each group. In the Moxi group, moxibustion was applied at "Baihui" (GV20) and "Yongquan" (KI1) for 30 min, once a day, 5 days a week for 4 weeks. The spatial learning memory ability was observed by the Morris water maze test. The relative expressions of IL-33 and ST2 in hippocampus were detected by Western blot. The positive expression of amyloid-ß (Aß), phosphorylated Tau (p-Tau), IL-33/ionized calcium binding adapter molecule 1(Iba-1), ST2/Iba-1, arginase 1 (Arg1)/Iba-1 and indu-cible nitric oxide synthase (iNOS)/Iba-1 in hippocampal CA1 region were detected by immunofluorescence. RESULTS: Compared with the control group, the escape latency of the mice in the model group was prolonged (P<0.001, P<0.01), the number of times to enter the effective area and the percentage of target quadrant swimming time were reduced (P<0.001), the positive expression of both Aß and p-Tau, the positive expression of iNOS/Iba-1 in the hippocampal CA1 region was increased (P<0.001), while the expression of IL-33 and ST2 protein in hippocampal tissue, the positive expression levels of IL-33/Iba-1, ST2/Iba-1 and Arg1/Iba-1 in hippocampal CA1 region were all decreased (P<0.05, P<0.001). After treatment, compared with the model group, the escape latency of the mice in the moxibustion group was shortened (P<0.001, P<0.01), the number of entries into the effective area and the percentage of target quadrant swimming time were increased (P<0.001), the positive expression of Aß and p-Tau in the hippocampal CA1 region, and the positive expression of iNOS/Iba-1 were decreased (P<0.001), while the expression of IL-33 and ST2 protein in the hippocampal tissue, the positive expression of IL-33/Iba-1, ST2/Iba-1 and Arg1/Iba-1 in hippocampal CA1 region were all increased (P<0.05, P<0.01, P<0.001). CONCLUSIONS: Moxibustion can improve the spatial learning and memory abilities, reduce the pathological deposition of Aß and p-Tau in APP/PS1 mice, which may be related to its function in up-regulating the IL-33/ST2 signaling pathway to regulate the polarization of microglia towards M2 direction.

Self-Reported Neurological Symptoms Two Years After Hospital Discharge Among COVID-19 Survivors.

Background: The acute stage of COVID-19 often presents with neurological manifestations. Objective: This study aims to investigate the long-term neurological effects on survivors. Methods: This study recruited 1,546 COVID-19 survivors from Wuhan, including 1,119 nonsevere cases and 427 severe survivors. Participants were interviewed two years after discharge to report their neurological symptoms. The neurological symptoms of COVID-19 were compared between survivors of severe and nonsevere COVID-19. Results: Among the 1,546 COVID-19 survivors, 44.24% discovered at least one neurological symptom. The most prevalent self-reported symptom was fatigue (28.33%), memory deficit (13.26%), attention deficit (9.96%), myalgia (8.34%), dizziness (3.82%), and headache (2.52%). Severe cases had higher incidences of fatigue, myalgia, memory deficit, attention deficit than nonsevere cases. Older age, severe COVID-19, and comorbidity burden were associated with long-term neurological symptoms. Conclusion: Neurological symptoms are common among COVID-19 survivors, especially in severe cases.

Periodontitis and NAFLD-related diseases: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Epidemiological studies have shown an association between periodontitis and nonalcoholic fatty liver disease (NAFLD)-related diseases. However, a causal relationship between these two diseases remains unclear. To examine the causal relationship between these two diseases, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis using genetic markers as proxies. METHODS: Statistical summary was obtained from a large genome-wide association study (GWAS) on NAFLD (N = 342,499), nonalcoholic steatohepatitis (NASH, N = 342,499), fibrosis (N = 339,081), cirrhosis (N = 342,499), fibrosis/cirrhosis (N = 334,553), and periodontitis (N = 34,615) in the European ancestry. The inverse variance weighted (IVW) method was used as the main method to estimate the bidirectional association. Sensitivity analysis was performed to evaluate the rigidity of the results. RESULTS: Limited evidence indicated positive causal associations between genetically predicted NAFLD and periodontitis (IVW odds ratio [OR], 1.094; 95% confidence interval [CI], 1.006-1.189; p = 0.036) and between cirrhosis and periodontitis (IVW OR, 1.138; 95% CI, 1.001-1.294; p = 0.048). However, the opposite trend did not indicate a causative effect of periodontitis on NAFLD-related diseases. The sensitivity analysis revealed no obvious pleiotropy or heterogeneity. CONCLUSIONS: Our MR analysis provides new evidence in favor of the moderate causal impact of NAFLD on periodontitis. The causal effects of periodontitis on NAFLD-related diseases warrant further investigation.

STAT3-EphA7 axis contributes to the progression of esophageal squamous cell carcinoma.

BACKGROUND: Our previous study has revealed that EphA7 was upregulated in patient-derived esophageal squamous cell carcinoma (ESCC) xenografts with hyper-activated STAT3, but its mechanism was still unclear. MATERIALS AND METHODS: To assess the association between EphA7 and STAT3, western blotting, immunofluorescence, ChIP assay, and qRT-PCR were conducted. Truncated mutation and luciferase assay were performed to examine the promoter activity of EphA7. CCK-8 assay and colony formation were performed to assess the proliferation of ESCC. Cell-derived xenograft models were established to evaluate the effects of EphA7 on ESCC tumor growth. RNA-seq analyses were used to assess the effects of EphA7 on related signals. RESULTS: In this study, EphA7 was found upregulated in ESCC cell lines with high STAT3 activation, and immunofluorescence also showed that EphA7 was co-localized with phospho-STAT3 in ESCC cells. Interestingly, suppressing STAT3 activation by the STAT3 inhibitor Stattic markedly inhibited the protein expression of EphA7 in ESCC cells, in contrast, activation of STAT3 by IL-6 obviously upregulated the protein expression of EphA7. Moreover, the transcription of EphA7 was also mediated by the activation of STAT3 in ESCC cells, and the -2000∼-1500 region was identified as the key promoter of EphA7. Our results also indicated that EphA7 enhanced the cell proliferation of ESCC, and silence of EphA7 significantly suppressed ESCC tumor growth. Moreover, EphA7 silence markedly abolished STAT3 activation-derived cell proliferation of ESCC. Additionally, RNA-seq analyses indicated that several tumor-related signaling pathways were significantly changed after EphA7 downregulation in ESCC cells. CONCLUSION: Our results showed that the transcriptional expression of EphA7 was increased by activated STAT3, and the STAT3 signaling may act through EphA7 to promote the development of ESCC.

Electroacupuncture alleviates ulcerative colitis by targeting CXCL1: evidence from the transcriptome and validation.

Background: We aimed to use transcriptomics, bioinformatics analysis, and core gene validation to identify the core gene and potential mechanisms for electroacupuncture (EA) treatment of ulcerative colitis (UC). Materials and methods: EA was performed in mice after induction of UC via dextran sodium sulfate. Body weight, disease activity index (DAI), colon length, and hematoxylin-eosin of the colon tissue were used to evaluate the effects of EA. Mice transcriptome samples were analyzed to identify the core genes, and further verified with human transcriptome database; the ImmuCellAI database was used to analyze the relationship between the core gene and immune infiltrating cells (IICs); and immunofluorescence was used to verify the results. Results: EA could reduce DAI and histological colitis scores, increase bodyweight and colon length, and improve the expression of local and systemic proinflammatory factors in the serum and colon of UC mice. Eighteen co-differentially expressed genes were identified by joint bioinformatics analyses of mouse and human transcriptional data; Cxcl1 was the core gene. EA affected IICs by inhibiting Cxcl1 expression and regulated the polarization of macrophages by affecting the Th1 cytokine IFN-γ, inhibiting the expression of CXCL1. Conclusions: CXCL1 is the target of EA, which is associated with the underlying immune mechanism related to Th1 cytokine IFN-γ.

Fit accuracy in the rest region of RPDs fabricated by digital technologies and conventional lost-wax casting: a systematic review and meta-analysis.

BACKGROUND: Digital technologies have recently been introduced into the fabrication of removable partial dentures (RPDs). However, it is still unclear whether the digitally fabricated RPDs fit better than conventionally cast ones in the rest region. The aim of this study was to evaluate the fit accuracy in the rest region of RPDs fabricated by digital technologies and compare it to those made by conventional lost-wax (CLW) technique. METHODS: A comprehensive search was conducted in Cochrane Library, PubMed, EMbase, Web of Science and SpringerLink. Studies published up to August 2022 were collected. Two authors analyzed the studies independently and assessed the risk of bias on the modified methodological index for non-randomized studies (MINORS) scale. The mean values of gap distance between rests and corresponding rest seats of each study were extracted as outcome. A random-effects model at a significance level of P < 0.05 was used in the global comparison and subgroup analysis was carried out. RESULTS: Overall, 11 articles out of 1214 complied with the inclusion criteria and were selected, including 2 randomized controlled trials (RCTs), 1 non-randomized clinical trial and 8 in vitro studies. Quantitative data from Meta-analysis revealed that fit accuracy in the rest region of RPDs fabricated with CLW showed no statistically significant difference with digital techniques (SMD = 0.33, 95%CI (-0.18, 0.83), P = 0.21). Subgroup analysis revealed a significantly better fit accuracy of CLW-fabricated RPDs in the rest region than either additive manufacturing (AM) groups or indirect groups (P = 0.03, P = 0.00), in which wax or resin patterns are milled or printed before conventional casting. While milled RPDs fit significantly better than cast ones in the rest region (P = 0.00). With digital relief and heat treatment, hybrid manufactured (HM) clasps obtained better fit accuracy in the rest region (P < 0.05). In addition, finishing and polishing procedure had no significant influence in the fit accuracy in all groups (P = 0.83). CONCLUSIONS: RPDs fabricated by digital technologies exhibit comparable fit accuracy in rest region with those made by CLW. Digital technologies may be a promising alternative to CLW for the fabrication of RPDs and additional studies are recommended to provide stronger evidence. TRIAL REGISTRATION: CRD42020201313.