Higher-order topological states in T-graphene and their realization in photonic crystals.

Higher-order topological states extend the power of nontrivial topological states beyond the bulk-edge correspondence. Here we study the higher-order topological states (corner states) in an open-boundary two-dimensional T-graphene lattice. Unlike the common zero-energy corner states, our findings reveal non-zero energy corner states in such lattice systems, and the energy could be controlled by modifying the hopping parameters. Moreover, the corner states could be transferred away from the lattice corners by designing the position-specific vacancy defects. The strong robustness of the corner states is also demonstrated against the uniaxial strain and vacancy defects, respectively. A plasmonic crystal is constructed to testify to the theory, in which the corner states are realized in optical modes and their higher-order topological properties are verified. Our results open the avenue of corner-states engineering, which holds significant physical implications of higher-order topological states for the design of photonic and electronic devices with specialized functionalities.

Anomalous Correlation between Thermal Conductivity and Elastic Modulus in Two-Dimensional Hybrid Metal Halide Perovskites.

Device-level implementation of soft materials for energy conversion and thermal management demands a comprehensive understanding of their thermal conductivity and elastic modulus to mitigate thermo-mechanical challenges and ensure long-term stability. Thermal conductivity and elastic modulus are usually positively correlated in soft materials, such as amorphous macromolecules, which poses a challenge to discover materials that are either soft and thermally conductive or hard and thermally insulative. Here, we show anomalous correlations of thermal conductivity and elastic modulus in two-dimensional (2D) hybrid organic-inorganic perovskites (HOIP) by engineering the molecular interactions between organic cations. By replacing conventional alkyl-alkyl and aryl-aryl type organic interactions with mixed alkyl-aryl interactions, we observe an enhancement in elastic modulus with a reduction in thermal conductivity. This anomalous dependence provides a route to engineer thermal conductivity and elastic modulus independently and a guideline to search for better thermal management materials. Further, introducing chirality into the organic cation induces a molecular packing that leads to the same thermal conductivity and elastic modulus regardless of the composition across all half-chiral 2D HOIPs. This finding provides substantial leeway for further investigations in chiral 2D HOIPs to tune optoelectronic properties without compromising thermal and mechanical stability.

Non-flooding conditions caused by water table drawdown alter microbial network complexity and decrease multifunctionality in alpine wetland soils.

Several soil functions of alpine wetland depend on microbial communities, including carbon storage and nutrient cycling, and soil microbes are highly sensitive to hydrological conditions. Wetland degradation is often accompanied by a decline in water table. With the water table drawdown, the effects of microbial network complexity on various soil functions remain insufficiently understood. In this research, we quantified soil multifunctionality of flooded and non-flooded sites in the Lalu Wetland on the Tibetan Plateau. We employed high-throughput sequencing to investigate the microbial community responses to water table depth changes, as well as the relationships between microbial network properties and soil multifunctionality. Our findings revealed a substantial reduction in soil multifunctionality at both surface and subsurface soil layers (0-20 cm and 20-40 cm) in non-flooded sites compared to flooded sites. The α-diversity of bacteria in the surface soil of non-flooded sites was significantly lower than that in flooded sites. Microbial network properties (including the number of nodes, number of edges, average degree, density, and modularity of co-occurrence networks) exhibited significant correlations with soil multifunctionality. This study underscores the adverse impact of non-flooded conditions resulting from water table drawdown on soil multifunctionality in alpine wetland soils, driven by alterations in microbial community structure. Additionally, we identified soil pH and moisture content as pivotal abiotic factors influencing soil multifunctionality, with microbial network complexity emerging as a valuable predictor of multifunctionality.

Enterotoxin-related genes PPFIA4 and SCN3B promote colorectal cancer development and progression.

To identify the role of enterotoxin-related genes in colorectal cancer (CRC) development and progression. Upregulated differentially expressed genes shared by three out of five Gene Expression Omnibus (GEO) data sets were included to screen the key enterotoxin-induced oncogenes (EIOGs) according to criteria oncogene definition, enrichment, and protein-protein interaction (PPI) network analysis, followed by prognosis survival, immune infiltration, and protential drugs analyses was performed via integration of RNA-sequencing data and The Cancer Genome Atlas-derived clinical profiles. We screened nine common key EIOGs from at least three GEO data sets. A Cox proportional hazards regression models verified that more alive cases, decreased overall survival, and highest 4-year survival prediction in CRC patients with high-risk score. Protein tyrosine phosphatase receptor type F polypeptide-interacting protein alpha-4 (PPFIA4), STY11, SCN3B, and SPTBN5 were shared in the same PPI network. Immune infiltration results showed that SCN3B and synaptotagmin 11 expression were obviously associated with B cell, macrophage, myeloid dendritic cell, neutrophils, and T cell CD4+ and CD8+ in both colon adenocarcinoma and rectal adenocarcinoma. CHIR-99021, MLN4924, and YK4-279 were identified as the potential drugs for treatment. Finally, upregulated EIOGs genes PPFIA4 and SCN3B were found in colon adenocarcinoma and PPFIA4 and SCN3B were proved to promote cell proliferation and migration in vitro. We demonstrated here that EIOGs promoting a malignancy phenotype was related with poor survival and prognosis in CRC, which might be served as novel therapeutic targets in CRC management.

Mechanism of non-thermal atmospheric plasma in anti-tumor: influencing intracellular RONS and regulating signaling pathways.

Non-thermal atmospheric plasma (NTAP) has been proven to be an effective anti-tumor tool, with various biological effects such as inhibiting tumor proliferation, metastasis, and promoting tumor cell apoptosis. At present, the main conclusion is that ROS and RNS are the main effector components of NTAP, but the mechanisms of which still lack systematic summary. Therefore, in this review, we first summarized the mechanism by which NTAP directly or indirectly causes an increase in intracellular RONS concentration, and the multiple pathways dysregulation (i.e. NRF2, PI3K, MAPK, NF-κB) induced by intracellular RONS. Then, we generalized the relationship between NTAP induced pathways dysregulation and the various biological effects it brought. The summary of the anti-tumor mechanism of NTAP is helpful for its further research and clinical transformation.

Non-thermal atmospheric plasma (NTAP) acts on NADPH oxidase and catalase.The feeding gas and parameters of NTAP affect its impacts on the signaling pathways.The impacts of NTAP and RONS on pathways are not always consistent.NTAP can trigger various anti-tumor biological effects.

Utility of somatosensory- and motor-evoked potential change thresholds in surgical treatment for thoracic spinal stenosis based on different pathologies.

BACKGROUND CONTEXT: Thoracic spinal stenosis (TSS) is secondary to different pathologies that differ in clinical characteristics and surgical outcomes. PURPOSE: This study aimed to determine the optimal warning thresholds for combined somatosensory-evoked potentials (SSEP) and motor-evoked potentials (MEP) for predicting postoperative neurological deterioration in surgical treatment for TSS based on different pathologies. Additionally, we explored the correlation between SSEP/MEP monitoring and postoperative spinal neurological function. STUDY SETTING: Retrospective study. PATIENT SAMPLE: Two hundred and five patients. OUTCOME MEASURES: We obtained perioperative modified Japanese Orthopedic Association (mJOA) scores to assess spinal neurological function. METHODS: The data collected in this study included demographic data, intraoperative neurophysiological monitoring (IONM) signals, and perioperative neurological function assessments. To determine the optimal IONM warning threshold, a receiver operating characteristic (ROC) curve was used. Additionally, Pearson correlation analysis was conducted to determine the correlation between IONM signals and clinical neurological conditions. RESULTS: A total of 205 consecutive patients were eligible. Forty-one patients had thoracic disc herniation (TDH), 14 had ossification of the posterior longitudinal ligament (OPLL), 124 had ossification of the ligamentum flavum (OLF), and 26 had OPLL+OLF. The mean mJOA scores before surgery and 3 months after surgery were 7.0 and 7.9, respectively, resulting in a mean mJOA recovery rate (RR) of 23.1%. The average postoperative mJOA RRs for patients with TDH, OPLL, OLF, and OPLL+OLF were 24.8%, 10.4%, 26.8%, and 11.2%, respectively. Patients with OPLL+OLF exhibited a more stringent threshold for IONM changes. This included a lower amplitude cutoff value (a decrease of 49.0% in the SSEP amplitude and 57.5% in the MEP amplitude for short-term prediction) and a shorter duration of waveform change (19.5 minutes for SSEP and 22.5 minutes for MEP for short-term prediction). On the other hand, patients with TDH had more lenient IONM warning criteria (a decrease of 49.0% in SSEP amplitude and 77.5% in MEP amplitude for short-term prediction; durations of change of 25.5 minutes for SSEP and 32.5 minutes for MEP). However, OPLL patients or OLF patients had moderate and similar IONM warning thresholds. Additionally, there was a stronger correlation between the SSEP amplitude variability ratio and the JOA RR in OPLL+OLF patients, while the correlation was stronger between the MEP amplitude variability ratio and the JOA RR for the other three TSS pathologies. CONCLUSIONS: Optimal IONM change criteria for prediction vary depending on different TSS pathologies. The optimal monitoring strategy for prediction varies depending on TSS pathologies.

Antimicrobial peptides in bone regeneration: mechanism and potential.

INTRODUCTION: Antimicrobial peptides (AMPs) are small-molecule peptides with a unique antimicrobial mechanism. Other notable biological activities of AMPs, including anti-inflammatory, angiogenesis, and bone formation effects, have recently received widespread attention. These remarkable bioactivities, combined with the unique antimicrobial mechanism of action of AMPs, have led to their increasingly important role in bone regeneration. AREAS COVERED: In this review, on the one hand, we aimed to summarize information about the AMPs that are currently used for bone regeneration by reviewing published literature in the PubMed database. On the other hand, we also highlight some AMPs with potential roles in bone regeneration and their possible mechanisms of action. EXPERT OPINION: The translation of AMPs to the clinic still faces many problems, but their unique antimicrobial mechanisms and other conspicuous biological activities suggest great potential. An in-depth understanding of the structure and mechanism of action of AMPs will help us to subsequently combine AMPs with different carrier systems and perform structural modifications to reduce toxicity and achieve stable release, which may be a key strategy for facilitating the translation of AMPs to the clinic.

Primary pancreatic peripheral T-cell lymphoma: A case report.

BACKGROUND: Primary pancreatic lymphoma (PPL) is an exceedingly rare tumor with limited mention in scientific literature. The clinical manifestations of PPL are often nonspecific, making it challenging to distinguish this disease from other pancreatic-related diseases. Chemotherapy remains the primary treatment for these individuals. CASE SUMMARY: In this case study, we present the clinical details of a 62-year-old woman who initially presented with vomiting, abdominal pain, and dorsal pain. On further evaluation through positron emission tomography-computed tomography, the patient was considered to have a pancreatic head mass. However, subsequent endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) revealed that the patient had pancreatic peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin, decitabine, and oxaliplatin (brentuximab vedotin and Gemox). The patient had significant improvement in radiological findings at the end of the first cycle. CONCLUSION: Primary pancreatic PTCL-NOS is a malignant and heterogeneous lymphoma, in which the clinical manifestations are often nonspecific. It is difficult to diagnose, and the prognosis is poor. Imaging can only be used for auxiliary diagnosis of other diseases. With the help of immunostaining, EUS-FNA could be used to aid in the diagnosis of PPL. After a clear diagnosis, chemotherapy is still the first-line treatment for such patients, and surgical resection is not recommended. A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma. However, identifying new CD30-targeted therapies for different types of lymphoma is urgently needed. In the future, further research on antitumor therapy should be carried out to improve the survival prognosis of such patients.

Combination of bone marrow mesenchymal stem cells and moxibustion restores cyclophosphamide-induced premature ovarian insufficiency by improving mitochondrial function and regulating mitophagy.

BACKGROUND: Premature ovarian insufficiency (POI) is a major cause of infertility. In this study, we aimed to investigate the effects of the combination of bone marrow mesenchymal stem cells (BMSCs) and moxibustion (BMSCs-MOX) on POI and evaluate the underlying mechanisms. METHODS: A POI rat model was established by injecting different doses of cyclophosphamide (Cy). The modeling of POI and the effects of the treatments were assessed by evaluating estrous cycle, serum hormone levels, ovarian weight, ovarian index, and ovarian histopathological analysis. The effects of moxibustion on BMSCs migration were evaluated by tracking DiR-labeled BMSCs and analyzing the expression of chemokines stromal cell-derived factor 1 (Sdf1) and chemokine receptor type 4 (Cxcr4). Mitochondrial function and mitophagy were assessed by measuring the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, and the mitophagy markers (Drp1, Pink1, and Parkin). Furthermore, the mitophagy inhibitor Mdivi-1 and the mitophagy activator CCCP were used to confirm the role of mitophagy in Cy-induced ovarian injury and the underlying mechanism of combination therapy. RESULTS: A suitable rat model of POI was established using Cy injection. Compared to moxibustion or BMSCs transplantation alone, BMSCs-MOX showed improved outcomes, such as reduced estrous cycle disorders, improved ovarian weight and index, normalized serum hormone levels, increased ovarian reserve, and reduced follicle atresia. Moxibustion enhanced Sdf1 and Cxcr4 expression, promoting BMSCs migration. BMSCs-MOX reduced ROS levels; upregulated MMP and ATP levels in ovarian granulosa cells (GCs); and downregulated Drp1, Pink1, and Parkin expression in ovarian tissues. Mdivi-1 significantly mitigated mitochondrial dysfunction in ovarian GCs and improved ovarian function. CCCP inhibited the ability of BMSCs-MOX treatment to regulate mitophagy and ameliorate Cy-induced ovarian injury. CONCLUSIONS: Moxibustion enhanced the migration and homing of BMSCs following transplantation and improves their ability to repair ovarian damage. The combination of BMSCs and moxibustion effectively reduced the excessive activation of mitophagy, which helped prevent mitochondrial damage, ultimately improving ovarian function. These findings provide a novel approach for the treatment of pathological ovarian aging and offer new insights into enhancing the efficacy of stem cell therapy for POI patients.

Changes in soil oxidase activity induced by microbial life history strategies mediate the soil heterotrophic respiration response to drought and nitrogen enrichment.

Drought and nitrogen deposition are two major climate challenges, which can change the soil microbial community composition and ecological strategy and affect soil heterotrophic respiration (Rh). However, the combined effects of microbial community composition, microbial life strategies, and extracellular enzymes on the dynamics of Rh under drought and nitrogen deposition conditions remain unclear. Here, we experimented with an alpine swamp meadow to simulate drought (50% reduction in precipitation) and multilevel addition of nitrogen to determine the interactive effects of microbial community composition, microbial life strategy, and extracellular enzymes on Rh. The results showed that drought significantly reduced the seasonal mean Rh by 40.07%, and increased the Rh to soil respiration ratio by 22.04%. Drought significantly altered microbial community composition. The ratio of K- to r-selected bacteria (BK:r) and fungi (FK:r) increased by 20 and 91.43%, respectively. Drought increased hydrolase activities but decreased oxidase activities. However, adding N had no significant effect on microbial community composition, BK:r, FK:r, extracellular enzymes, or Rh. A structural equation model showed that the effects of drought and adding nitrogen via microbial community composition, microbial life strategy, and extracellular enzymes explained 84% of the variation in Rh. Oxidase activities decreased with BK:r, but increased with FK:r. Our findings show that drought decreased Rh primarily by inhibiting oxidase activities, which is induced by bacterial shifts from the r-strategy to the K-strategy. Our results highlight that the indirect regulation of drought on the carbon cycle through the dynamic of bacterial and fungal life history strategy should be considered for a better understanding of how terrestrial ecosystems respond to future climate change.

Transcriptome-wide 1-methyladenosine functional profiling of messenger RNA and long non-coding RNA in bladder cancer.

Introduction: Post-transcriptional RNA modifications are crucial regulators of tumor development and progression. In many biological processes, N1-methyladenosine (m1A) plays a key role. However, little is known about the links between chemical modifications of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) and their function in bladder cancer (BLCA). Methods: Methylated RNA immunoprecipitation sequencing and RNA sequencing were performed to profile mRNA and lncRNA m1A methylation and expression in BLCA cells, with or without stable knockdown of the m1A methyltransferase tRNA methyltransferase 61A (TRMT61A). Results: The analysis of differentially methylated gene sites identified 16,941 peaks, 6,698 mRNAs, and 10,243 lncRNAs in the two groups. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the differentially methylated and expressed transcripts showed that m1A-regulated transcripts were mainly related to protein binding and signaling pathways in cancer. In addition, the differentially genes were identified that were also differentially m1A-modified and identified 14 mRNAs and 19 lncRNAs. Next, these mRNAs and lncRNAs were used to construct a lncRNA-microRNA-mRNA competing endogenous RNA network, which included 118 miRNAs, 15 lncRNAs, and 8 mRNAs. Finally, the m1A-modified transcripts, SCN2B and ENST00000536140, which are highly expressed in BLCA tissues, were associated with decreased overall patient survival. Discussion: This study revealed substantially different amounts and distributions of m1A in BLCA after TRMT61A knockdown and predicted cellular functions in which m1A may be involved, providing evidence that implicates m1A mRNA and lncRNA epitranscriptomic regulation in BLCA tumorigenesis and progression.

Treatment of ureteropelvic junction obstruction in patients with renal calculi via laparoscopic pyeloplasty and flexible vacuum-assisted ureteral access sheath ureteroscopy: a multicenter retrospective observational study.

BACKGROUND: Ureteropelvic junction obstruction (UPJO) is a common obstructive disease of the urinary tract. UPJO patients commonly exhibit coexistent renal calculi. The main aim of therapy is to relieve the obstruction and remove the stones at the same time. METHODS: This retrospective study included 110 patients diagnosed with UPJO coexisting with multiple renal calculi at Shanxi Bethune Hospital and the First Hospital of Shanxi Medical University between March 2016 and January 2022. Patients were divided according to the methods used for dealing with UPJO and renal calculi. In Group A, patients underwent traditional open pyeloplasty and pyelolithotomy. In Group B, patients underwent percutaneous nephrolithotomy first and then laparoscopic pyeloplasty. In Group C, patients underwent flexible cystoscopy to remove stones and then laparoscopic pyeloplasty. In Group D, patients underwent flexible vacuum-assisted ureteral access sheath (FV-UAS)assisted flexible ureteroscopy (f-URS) and underwent laparoscopic pyeloplasty. The stones were broken up using a holmium laser. The pyeloplasty success rate, stone clearance rate, operation time, bleeding amount, complication occurrence rate, postsurgical pain, length of stay, and hospitalization cost were compared between the groups. The follow-up period was at least 2 years. RESULTS: The use of f-URS and the FV-UAS, significantly increased the renal stone clearance rate and significantly reduced the complication incidence and operation time in UPJO patients with multiple coexisting renal calculi. CONCLUSIONS: Laparoscopic pyeloplasty combined with f-URS and FV-UAS is safe and effective for treating UPJO in patients complicated by renal caliceal stones. TRIAL REGISTRATION: Retrospectively registered.

Chemical Constituents from the Heartwood of Solanum Verbascifolium L. And Their Anti-Inflammatory Activities Combined Network Pharmacology.

Phytochemical studies on 95 % ethanol extract of the heartwood of Solanum verbascifolium L. resulted in the isolation of one new amide derivative (1), and 21 known phenylpropanoids compounds. The structures were characterized by spectral analysis and high-resolution mass spectrometric analysis. The anti-inflammatory activity of amide compounds 1-4 and 6-9 by investigating their impact on the release of nitric oxide (NO) in MH-S cells. Our findings unveiled significant inhibitory effects on NO secretion. Compound 1 exhibited robust dose-dependent suppression, with pronounced inhibition observed at both 20 µM (P<0.01) and 40 µM (P<0.01). Furthermore, compound 9 demonstrated noteworthy inhibitory effects at 40 µM (P<0.01). Similarly, compounds 3 and 4 displayed substantial inhibition of NO secretion at the same concentration, although the significance level was slightly lower (P<0.05). It is expected that there is a substantial association between the anti-inflammatory activities of amides and their targets, specifically PTGS2, by combining network pharmacology and molecular docking techniques. This discovery emphasizes amides' potential as an interesting subject for additional study in the realm of anti-inflammatory medications.

Case report: Ectopic corpus cavernosum presented as bladder tumor in a 3-year-old boy.

Background: Ectopic tissue is rarely found in the bladder for adults. Currently, there have been reports of ectopic prostate and colon tissue in the bladder. These ectopic tissues are manifested as a bladder mass and cause lower urinary tract symptoms. However, the ectopic corpus cavernosum in the bladder has never been reported, and its clinical characteristics and treatment have not been explored yet. Case summary: A 3-year-old boy was admitted to the hospital due to 1 month of urinary frequency. The physical examination was unremarkable. Urine analysis from other hospitals showed an elevated urine white blood cell count of 17.9/ul. In addition, ultrasound indicated a possible bladder mass. CT and MRI showed a well-margined lesion (1.9×1.9 cm) in the bladder trigone. Through preoperative imaging, we diagnosed a bladder tumor (inclined towards benign). The transurethral resection of the bladder tumor was performed. Unfortunately, the surgery was unsuccessful due to the difficulty in removing the excised tissue through the urethra. Subsequently, bladder incision and tumor resection were performed. The tumor was successfully removed. Surprisingly, the postoperative pathology showed that the tumor tissue was corpus cavernosum. The pathological diagnosis was ectopic corpus cavernosum in the bladder. No complications were found after the operation, and no recurrence was observed during follow-up. Conclusion: The ectopic corpus cavernosum in the bladder has never been reported for children, which is presented as a benign tumor with rapid proliferation and large size. Surgery is recommended. However, the transurethral resection of bladder tumors is difficult to perform due to narrow urethra and limited surgical instruments. Bladder incision and tumor resection may be preferred.

Inflammatory cell death PANoptosis is induced by the anti-cancer curaxin CBL0137 via eliciting the assembly of ZBP1-associated PANoptosome.

OBJECTIVE: PANoptosis, a new form of regulated cell death, concomitantly manifests hallmarks for pyroptosis, apoptosis, and necroptosis. It has been usually observed in macrophages, a class of widely distributed innate immune cells in various tissues, upon pathogenic infections. The second-generation curaxin, CBL0137, can trigger necroptosis and apoptosis in cancer-associated fibroblasts. This study aimed to explore whether CBL0137 induces PANoptosis in macrophages in vitro and in mouse tissues in vivo. METHODS: Bone marrow-derived macrophages and J774A.1 cells were treated with CBL0137 or its combination with LPS for indicated time periods. Cell death was assayed by propidium iodide staining and immunoblotting. Immunofluorescence microscopy was used to detect cellular protein distribution. Mice were administered with CBL0137 plus LPS and their serum and tissues were collected for biochemical and histopathological analyses, respectively. RESULTS: The results showed that CBL0137 alone or in combination with LPS induced time- and dose-dependent cell death in macrophages, which was inhibited by a combination of multiple forms of cell death inhibitors but not each alone. This cell death was independent of NLRP3 expression. CBL0137 or CBL0137 + LPS-induced cell death was characterized by simultaneously increased hallmarks for pyroptosis, apoptosis and necroptosis, indicating that this is PANoptosis. Induction of PANoptosis was associated with Z-DNA formation in the nucleus and likely assembly of PANoptosome. ZBP1 was critical in mediating CBL0137 + LPS-induced cell death likely by sensing Z-DNA. Moreover, intraperitoneal administration of CBL0137 plus LPS induced systemic inflammatory responses and caused multi-organ (including the liver, kidney and lung) injury in mice due to induction of PANoptosis in these organs. CONCLUSIONS: CBL0137 alone or plus inflammatory stimulation induces PANoptosis both in vitro and in vivo, which is associated with systemic inflammatory responses in mice.

Exploring the therapeutic potential of isoorientin in the treatment of osteoporosis: a study using network pharmacology and experimental validation.

BACKGROUND: Isoorientin (ISO) is a glycosylated flavonoid with antitumor, anti-inflammatory, and antioxidant properties. However, its effects on bone metabolism remain largely unknown. METHODS: In this study, we aimed to investigate the effects of ISO on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in vitro and bone loss in post-ovariectomy (OVX) rats, as well as to elucidate the underlying mechanism. First, network pharmacology analysis indicated that MAPK1 and AKT1 may be potential therapeutic targets of ISO and that ISO has potential regulatory effects on the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways, as well as oxidative stress. ISO was added to RAW264.7 cells stimulated by RANKL, and its effects on osteoclast differentiation were evaluated using tartrate-resistant acid phosphatase (TRAP) staining, TRAP activity measurement, and F-actin ring analysis. Reactive oxygen species (ROS) production in osteoclasts was detected using a ROS assay kit. The effects of ISO on RANKL-triggered molecular cascade response were further investigated by Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining. In addition, the therapeutic effects of ISO were evaluated in vivo. RESULTS: ISO inhibited osteoclastogenesis in a time- and concentration-dependent manner. Mechanistically, ISO downregulated the expression of the main transcription factor for osteoclast differentiation by inhibiting MAPK and PI3K/AKT1 signaling pathways. Moreover, ISO exhibited protective effects in OVX-induced bone loss rats. This was consistent with the results derived from network pharmacology. CONCLUSION: Our findings suggest a potential therapeutic utility of ISO in the management of osteoclast-associated bone diseases, including osteoporosis.

Gallium nitride-based geometric and propagation metasurfaces for vortex beam emissions.

This work experimentally demonstrates the highly-efficient geometric and propagation metasurfaces for vortex beam emissions. These metasurfaces are respectively composed of high-aspect-ratio fin-like and cylindrical gallium nitride (GaN) meta-atoms. Remarkably, the optimized configuration of the fin-like GaN meta-atoms achieves a cross-polarization transmission efficiency of up to 99 %. Similarly, the cylindrical GaN meta-atoms exhibit an average co-polarization transmission efficiency of 97 %. Both metasurfaces, designed for vortex beam emission, exhibit annular intensity converging capabilities at distinct wavelengths in the visible. Notably, the geometric metasurface shows achromatic annular intensity distributions over a continuous wavelength range up to 100 nm, in sharp contrast to the propagation metasurface, which is subject to inherent wavelength dispersion limitations.

Visible-light-promoted difluoroamidated oxindole synthesis via electron donor-acceptor complexes.

A method involving a metal-free visible-light-promoted synthesis was developed for the construction of difluoroalkylated oxindoles with N-phenylacrylamides and bromodifluoroacetamides as starting materials in the presence of N,N,N',N'-tetramethylethylenediamine (TMEDA). Twenty-four examples of the photochemical reaction were successfully performed, with good yields (44-99%) and excellent substrate adaptability. Mechanistic studies showed that the visible-light-promoted reaction involved a radical addition to N-phenylacrylamide, intramolecular cyclization, dehydrogenation, and rearomatization. The difluoroacetamide radical was produced as a result of electron transfer to bromodifluoroacetamides from the electron donor TMEDA in their electron-donor-acceptor (EDA) complexes under visible light irradiation. This protocol is a promising photochemical method due to its advantages of mild conditions, simple operation, wide substrate scope and high yields. And the obtained products may have great potential in the field of medicine.

Abnormal femoral trochlea morphology is a risk factor for secondary injury of anterior cruciate ligament after reconstruction.

Secondary injury of the anterior cruciate ligament (ACL) is a common concern after anterior cruciate ligament (ACL) reconstruction, and identification of morphological risk factors is essential to prevent these injuries. We hypothesized that abnormal femoral trochlea morphology is associated with secondary ACL injuries after reconstruction. This study aimed to investigate the relationship between femoral trochlear morphology and secondary ACL injuries after reconstruction. A retrospective analysis was conducted on 20 patients who experienced secondary ACL injuries after reconstruction in our hospital between 2017 and 2022 (experimental group), and 40 patients were included in the control group. The following femoral trochlear characteristics were compared between the 2 groups: medial condylar height (MCH), trochlear sulcus height (TSH), lateral condylar height (LCH), trochlear sulcus depth (TSD), trochlear sulcus angle (TSA), medial trochlear inclination (MTI), and lateral trochlear inclination (LTI). The study found that patients in the secondary ACL injury after reconstruction group exhibited the following differences when compared to the control group: decreased MCH (56.33 ±â€…3.52 vs 59.93 ±â€…3.24, P value = .015), decreased TSD (4.89 ±â€…1.56 vs 6.98 ±â€…1.23, P value ˂ .001), decreased MTI (12.54 ±â€…6.57 vs 19.45 ±â€…6.35, P value ˂ .001), and increased TSA (145.23 ±â€…9.76 vs 139.25 ±â€…8.42, P value ˂ .001). This study demonstrated a significant correlation between abnormal femoral trochlear morphological characteristics and secondary ACL injuries after reconstruction. Decreased MCH, TSD, and MTI along with increased TSA are associated with a higher risk of secondary ACL injury. These data could thus help identify individuals susceptible to secondary ACL injuries after reconstruction.

Myeloid zinc finger 1 knockdown promotes osteoclastogenesis and bone loss in part by regulating RANKL-induced ferroptosis of osteoclasts through Nrf2/GPX4 signaling pathway.

The overactivation of the osteoclasts is a crucial pathological factor in the development of osteoporosis. MZF1, belonging to the scan-zinc finger family, plays a significant role in various processes associated with tumor malignant progression and acts as an essential transcription factor regulating osteoblast expression. However, the exact role of MZF1 in osteoclasts has not been determined. In this study, the purpose of our study was to elucidate the role of MZF1 in osteoclastogenesis. First, we established MZF1-deficient female mice and evaluated the femur bone phenotype by micro-computed tomography and histological staining. Our findings indicate that MZF1-/- mice exhibited a low bone mass osteoporosis phenotype. RANKL could independently induce the differentiation of RAW264.7 cells into osteoclasts, and we found that the expression level of MZF1 protein decreased gradually. Then, the CRISPR/Cas 9 gene-editing technique was used to build a RAW264.7 cell model with MZF1 knockout, and RANKL was used to independently induce MZF1-/- and wild-type cells to differentiate into mature osteoclasts. Tartrate-resistant acid phosphatase staining and F-actin fluorescence results showed that the MZF1-/- group produced more tartrate-resistant acid phosphatase-positive mature osteoclasts and larger actin rings. The expression of osteoclast-associated genes (including tartrate-resistant acid phosphatase, CTSK, c-Fos, and NFATc1) was evaluated by reverse transcription quantitative polymerase chain reaction and Western blot. The expression of key genes of osteoclast differentiation in the MZF1-/- group was significantly increased. Furthermore, we found that cell viability was increased in the early stages of RANKL-induced cell differentiation in the MZF1-/- group cells. We examined some prevalent ferroptosis markers, including malondialdehyde, glutathione, and intracellular Fe, the active form of iron in the cytoplasm during the early stages of osteoclastogenesis. The results suggest that MZF1 may be involved in osteoclast differentiation by regulating RANKL-induced ferroptosis of osteoclasts. Collectively, our findings shed light on the essential involvement of MZF1 in the regulation of osteoclastogenesis in osteoporosis and provide insights into its potential underlying mechanism.