Intrathecal Fumagillin Alleviates Chronic Neuropathy-Induced Nociceptive Sensitization and Modulates Spinal Astrocyte-Neuronal Glycolytic and Angiogenic Proteins.

Nociceptive sensitization is accompanied by the upregulation of glycolysis in the central nervous system in neuropathic pain. Growing evidence has demonstrated glycolysis and angiogenesis to be related to the inflammatory processes. This study investigated whether fumagillin inhibits neuropathic pain by regulating glycolysis and angiogenesis. Fumagillin was administered through an intrathecal catheter implanted in rats with chronic constriction injury (CCI) of the sciatic nerve. Nociceptive, behavioral, and immunohistochemical analyses were performed to evaluate the effects of the inhibition of spinal glycolysis-related enzymes and angiogenic factors on CCI-induced neuropathic pain. Fumagillin reduced CCI-induced thermal hyperalgesia and mechanical allodynia from postoperative days (POD) 7 to 14. The expression of angiogenic factors, vascular endothelial growth factor (VEGF) and angiopoietin 2 (ANG2), increased in the ipsilateral lumbar spinal cord dorsal horn (SCDH) following CCI. The glycolysis-related enzymes, pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA) significantly increased in the ipsilateral lumbar SCDH following CCI on POD 7 and 14 compared to those in the control rats. Double immunofluorescence staining indicated that VEGF and PKM2 were predominantly expressed in the astrocytes, whereas ANG2 and LDHA were predominantly expressed in the neurons. Intrathecal infusion of fumagillin significantly reduced the expression of angiogenic factors and glycolytic enzymes upregulated by CCI. The expression of hypoxia-inducible factor-1α (HIF-1α), a crucial transcription factor that regulates angiogenesis and glycolysis, was also upregulated after CCI and inhibited by fumagillin. We concluded that intrathecal fumagillin may reduce the expression of ANG2 and LDHA in neurons and VEGF and PKM2 in the astrocytes of the SCDH, further attenuating spinal angiogenesis in neuropathy-induced nociceptive sensitization. Hence, fumagillin may play a role in the inhibition of peripheral neuropathy-induced neuropathic pain by modulating glycolysis and angiogenesis.

Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis.

The emergence of Poly (ADP-ribose) polymerase inhibitors (PARPi) has marked the beginning of a precise targeted therapy era for ovarian cancer. However, an increasing number of patients are experiencing primary or acquired resistance to PARPi, severely limiting its clinical application. Deciphering the underlying mechanisms of PARPi resistance and discovering new therapeutic targets is an urgent and critical issue to address. In this study, we observed a close correlation between glycolysis, tumor angiogenesis, and PARPi resistance in ovarian cancer. Furthermore, we discovered that the natural compound Paris saponin VII (PS VII) partially reversed PARPi resistance in ovarian cancer and demonstrated synergistic therapeutic effects when combined with PARPi. Additionally, we found that PS VII potentially hindered glycolysis and angiogenesis in PARPi-resistant ovarian cancer cells by binding and stabilizing the expression of RORα, thus further inhibiting ECM1 and interfering with the VEGFR2/FAK/AKT/GSK3ß signaling pathway. Our research provides new targeted treatment for clinical ovarian cancer therapy and brings new hope to patients with PARPi-resistant ovarian cancer, effectively expanding the application of PARPi in clinical treatment.

Transient crosslinking controls the condensate formation pathway within chromatin networks.

The network structure of densely packed chromatin within the nucleus of eukaryotic cells acts in concert with nonequilibrium processes. Using statistical physics simulations, we explore the control provided by transient crosslinking of the chromatin network by structural-maintenance-of-chromosome (SMC) proteins over (i) the physical properties of the chromatin network and (ii) condensate formation of embedded molecular species. We find that the density and lifetime of transient SMC crosslinks regulate structural relaxation modes and tune the sol-vs-gel state of the chromatin network, which imparts control over the kinetic pathway to condensate formation. Specifically, lower density, shorter-lived crosslinks induce sollike networks and a droplet-fusion pathway, whereas higher density, longer-lived crosslinks induce gellike networks and an Ostwald-ripening pathway.

Local Magnesium Sulfate Administration Ameliorates Nociception, Peripheral Inflammation, and Spinal Sensitization in a Rat Model of Incisional Pain.

OBJECTIVE: Postoperative pain remains one of the most common complaints after surgery, and appropriate treatments are limited. METHODS: We therefore investigated the effect of the anti-nociceptive properties of magnesium sulfate (MgSO4), an N-methyl-D-aspartate (NMDA) receptor antagonist, on incision-induced postoperative pain and peripheral and central nervous system inflammation. RESULTS: We found that local MgSO4 administration dose-dependently increases paw withdrawal latency, indicating reduced peripheral postoperative pain. Furthermore, MgSO4 inhibited the expression of interleukin-1ß (IL-1ß) and inducible nitric oxide synthase (iNOS) and phosphorylation of the NMDA receptor NR1 subunit in injured paw tissue and significantly attenuated microglial and astrocytic activation in the ipsilateral lumbar spinal cord dorsal horn. CONCLUSION: Locally administered MgSO4 has potential for development as an adjunctive therapy for preventing central nociceptive sensitization.

Depletion Strategies for Crystallized Layers of Two-Dimensional Nanosheets to Enhance Lithium-Ion Conductivity in Polymer Nanocomposites.

The assembly of long-range aligned structures of two-dimensional nanosheets (2DNSs) in polymer nanocomposites (PNCs) is in urgent need for the design of nanoelectronics and lightweight energy-storage materials of high conductivity for electricity or heat. These 2DNS are thin and exhibit thermal fluctuations, leading to an intricate interplay with polymers in which entropic effects can be exploited to facilitate a range of different assemblies. In molecular dynamics simulations of experimentally studied 2DNSs, we show that the layer-forming crystallization of 2DNSs is programmable by regulating the strengths and ranges of polymer-induced entropic depletion attractions between pairs of 2DNSs, as well as between single 2DNSs and a substrate surface, by exclusively tuning the temperature and size of the 2DNS. Enhancing the temperature supports the 2DNS-substrate depletion rather than crystallization of 2DNSs in the bulk, leading to crystallized layers of 2DNSs on the substrate surfaces. On the other hand, the interaction range of the 2DNS-2DNS depletion attraction extends further than the 2DNS-substrate attraction whenever the 2DNS size is well above the correlation length of the polymers, which results in a nonmonotonic dependence of the crystallization layer on the 2DNS size. It is demonstrated that the depletion-tuned crystallization layers of 2DNSs contribute to a conductive channel in which individual lithium ions (Li ions) migrate efficiently through the PNCs. This work provides statistical and dynamical insights into the balance between the 2DNS-2DNS and 2DNS-substrate depletion interactions in polymer-2DNS composites and highlights the possibilities to exploit depletion strategies in order to engineer crystallization processes of 2DNSs and thus to control electrical conductivity.

Mitochondrial ATP generation is more proteome efficient than glycolysis.

Metabolic efficiency profoundly influences organismal fitness. Nonphotosynthetic organisms, from yeast to mammals, derive usable energy primarily through glycolysis and respiration. Although respiration is more energy efficient, some cells favor glycolysis even when oxygen is available (aerobic glycolysis, Warburg effect). A leading explanation is that glycolysis is more efficient in terms of ATP production per unit mass of protein (that is, faster). Through quantitative flux analysis and proteomics, we find, however, that mitochondrial respiration is actually more proteome efficient than aerobic glycolysis. This is shown across yeast strains, T cells, cancer cells, and tissues and tumors in vivo. Instead of aerobic glycolysis being valuable for fast ATP production, it correlates with high glycolytic protein expression, which promotes hypoxic growth. Aerobic glycolytic yeasts do not excel at aerobic growth but outgrow respiratory cells during oxygen limitation. We accordingly propose that aerobic glycolysis emerges from cells maintaining a proteome conducive to both aerobic and hypoxic growth.

One-pot asymmetric living copolymerization-induced chiral self-assemblies and circularly polarized luminescence.

Controlled synthesis of conjugated block polymers enables the optimization of their self-assembly and may lead to distinct optical properties and functionalities. Herein, we report a direct chain extension of one-handed helical poly(acyl methane) with 1-ethynyl-4-iodo-2,5-bis(octyloxy)benzene, affording well-defined π-conjugated poly(acyl methane)-b-poly(phenylene ethynylene) copolymers. Although the distinct monomers are polymerized via different mechanisms, the one-pot copolymerization follows a living polymerization manner, giving the desired optically active block copolymers with controllable molar mass and low distribution. The block copolymerization induced chiral self-assembly simultaneously due to the one-handed helicity of the poly(acyl methane) block, giving spherical nanoparticles, one-handed helices, and chiral micelles with controlled dimensions regarding the composition of the generated copolymers. Interestingly, the chiral assemblies exhibit clear circularly polarized luminescence with tunable handedness and a high dissymmetric factor.

Galectin-7 Induction by EHMT2 Inhibition Enhances Immunity in Microsatellite Stability Colorectal Cancer.

BACKGROUND & AIMS: Although immunotherapy shows substantial advancement in colorectal cancer (CRC) with microsatellite instability high, it has limited efficacy for CRC with microsatellite stability (MSS). Identifying combinations that reverse immune suppression and prime MSS tumors for current immunotherapy approaches remains an urgent need. METHODS: An in vitro CRISPR screen was performed using coculture models of primary tumor cells and autologous immune cells from MSS CRC patients to identify epigenetic targets that could enhance immunotherapy efficacy in MSS tumors. RESULTS: We revealed EHMT2, a histone methyltransferase, as a potential target for MSS CRC. EHMT2 inhibition transformed the immunosuppressive microenvironment of MSS tumors into an immunomodulatory one by altering cytokine expression, leading to T-cell-mediated cytotoxicity activation and improved responsiveness to anti-PD1 treatment. We observed galectin-7 up-regulation upon EHMT2 inhibition, which converted a "cold" MSS tumor environment into a T-cell-inflamed one. Mechanistically, CHD4 repressed galectin-7 expression by recruiting EHMT2 to form a cotranscriptional silencing complex. Galectin-7 administration enhanced anti-PD1 efficacy in MSS CRC, serving as a potent adjunct cytokine therapy. CONCLUSIONS: Our findings suggest that targeting the EHMT2/galectin-7 axis could provide a novel combination strategy for immunotherapy in MSS CRC.

Statistical 3D morphology characterization of vaterite microspheres produced by engineered Escherichia coli.

Hollow vaterite microspheres are important materials for biomedical applications such as drug delivery and regenerative medicine owing to their biocompatibility, high specific surface area, and ability to encapsulate a large number of bioactive molecules and compounds. We demonstrated that hollow vaterite microspheres are produced by an Escherichia coli strain engineered with a urease gene cluster from the ureolytic bacteria Sporosarcina pasteurii in the presence of bovine serum albumin. We characterized the 3D nanoscale morphology of five biogenic hollow vaterite microspheres using 3D high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) tomography. Using automated high-throughput HAADF-STEM imaging across several sample tilt orientations, we show that the microspheres evolved from a smaller more ellipsoidal shape to a larger more spherical shape while the internal hollow core increased in size and remained relatively spherical, indicating that the microspheres produced by this engineered strain likely do not contain the bacteria. The statistical 3D morphology information demonstrates the potential for using biogenic calcium carbonate mineralization to produce hollow vaterite microspheres with controlled morphologies. STATEMENT OF SIGNIFICANCE: The nanoscale 3D structures of biomaterials determine their physical, chemical, and biological properties, however significant efforts are required to obtain a statistical understanding of the internal 3D morphology of materials without damaging the structures. In this study, we developed a non-destructive, automated technique that allows us to understand the nanoscale 3D morphology of many unique hollow vaterite microspheres beyond the spectroscopy methods that lack local information and microscopy methods that cannot interrogate the full 3D structure. The method allowed us to quantitatively correlate the external diameters and aspect ratios of vaterite microspheres with their hollow internal structures at the nanoscale. This work demonstrates the opportunity to use automated transmission electron microscopy to characterize nanoscale 3D morphologies of many biomaterials and validate the chemical and biological functionality of these materials.

Polyarylisocyanides Derived from an Alkyne-Pd(II) Catalyst as Robust Alignment Media with Excellent Enantiodiscimination.

The development of chiral alignment media for measuring anisotropic NMR parameters provides an opportunity to determine the absolute configuration of chiral molecules without the need for derivatization. However, chiral alignment media with a high and robust enantiodiscriminating property for a wide range of chiral molecules are still scarce. In this study, we synthesized cholesterol-end-functionalized helical polyisocyanides from a chiral monomer using a cholesterol-based alkyne-Pd(II) initiator. These stereoregular polyisocyanides form stable and weak anisotropic lyotropic liquid crystals (LLCs) in dichloromethane systems, exhibiting highly optical activities in both single left- and right-handed helices. The preparation process of the media was straightforward, and the aligning property of the LLCs could be controlled by adjusting the concentration and temperature. Using the chiral polyisocyanides, we extracted the residual dipolar coupling for an enantiomeric pair of isopinocampheol (IPC), as well as a number of pharmaceutical molecules, demonstrating excellent enantiodiscriminating properties for a broad range of chiral compounds.

Photoswitchable Enantioselective and Helix-Sense Controlled Living Polymerization.

A pair of enantiomeric photoswitchable PdII catalysts, alkyne-PdII /LR-azo and alkyne-PdII /LS-azo , were prepared via the coordination of alkyne-PdII and azobenzene-modified phosphine ligands LR-azo and LS-azo . Owing to the cis-trans photoisomerization of the azobenzene moiety, alkyne-PdII /LR-azo and alkyne-PdII /LS-azo exhibited different polymerization activities, helix-sense selectivities, and enantioselectivities during the polymerization of isocyanide monomers under irradiation of different wavelength lights. Furthermore, the achiral isocyanide monomer A-1 could be polymerized efficiently using alkyne-PdII /LR-azo under dark condition in a living/controlled manner. Further, it generated single right-handed helical poly-A-1m (LR-azo ), confirmed by the circular dichroism spectra and atomic force microscopy images. However, the polymerization of A-1 almost could not be initiated under 420 nm light in identical conditions of dark condition. Moreover, the photoswitchable catalyst alkyne-PdII /LR-azo exhibited high enantioselectivity for the polymerization of the racemates of L-1 and D-1, respectively. D-1 was polymerized preferentially under dark condition with a D-1/L-1 rate ratio of 70, yielding single right-handed polyisocyanides. Additionally, reversible enantioselectivity was observed under 420 nm light using alkyne-PdII /LR-azo , and the calculated polymerization rate ratio of L-1/D-1 was 57 because of the isomerization of the azobenzene moiety of the catalyst. Furthermore, alkyne-PdII /LS-azo showed opposite enantioselectivity and helix-sense selectivity during the polymerization of the racemates of L-1 and D-1.

Thermo-responsive chiral micelles as recyclable organocatalyst for asymmetric Rauhut-Currier reaction in water.

Developing eco-friendly chiral organocatalysts with the combined advantages of homogeneous catalysis and heterogeneous processes is greatly desired. In this work, a family of amphiphilic one-handed helical polyisocyanides bearing phosphine pendants is prepared, which self-assembles into well-defined chiral micelles in water and showed thermo-responsiveness with a cloud point of approximately 38.4 °C. The micelles with abundant phosphine moieties at the interior efficiently catalyze asymmetric cross Rauhut-Currier reaction in water. Various water-insoluble substrates are transferred to target products in high yield with excellent enantioselectivity. The yield and enantiomeric excess (ee) of the product generated in water are up to 90% and 96%, respectively. Meanwhile, the yields of the same R-C reaction catalyzed by the polymer itself in organic solvents is <16%, with an ee < 72%. The homogeneous reaction of the chiral micelles in water turns to heterogeneous at temperatures higher than the cloud point, and the catalyst precipitation facilitates product isolation and catalyst recovery. The polymer catalyst is recycled 10 times while maintaining activity and enantioselectivity.

Polymers with Circularly Polarized Luminescent Properties: Design, Synthesis, and Prospects.

Chiral materials with circularly polarized luminescence (CPL) have garnered significant attention owing to their distinctive luminescent properties and wide array of applications. CPL enables the selective emission of left and right circularly polarized light. The fluorescence quantum yield and dissymmetry factor play pivotal roles in the generation of CPL. Helical polymers exhibit immense promise as CPL materials due to their inherent chirality, structural versatility, modifiability, and capacity to incorporate diverse chromophores. This Review provides a brief review of the synthesis of CPL materials based on helical polymers. The CPL can be realized by aggregation-induced CPL of non-emissive helical polymers, and helices bearing chromophores on the pendants and on the chain end. Furthermore, future challenges and potential applications of CPL materials are summarized and discussed.

Cinnamaldehyde Alleviates Bone Loss by Targeting Oxidative Stress and Mitochondrial Damage via the Nrf2/HO-1 Pathway in BMSCs and Ovariectomized Mice.

Osteoporosis (OP) is typically brought on by disruption of bone homeostasis. Excessive oxidative stress and mitochondrial dysfunction are believed to be the primary mechanisms underlying this disorder. Therefore, in order to restore bone homeostasis effectively, targeted treatment of oxidative stress and mitochondrial dysfunction is necessary. Cinnamaldehyde (CIN), a small molecule that acts as an agonist for the nuclear factor erythroid 2-related factor (Nrf2), has been found to possess antiapoptotic, anti-inflammatory, and antioxidant properties. We found that CIN, while rescuing apoptosis, can also reduce the accumulation of reactive oxygen species (ROS) to improve mitochondrial dysfunction and thus restore the osteogenic differentiation potential of BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The role of CIN was preliminarily considered to be a consequence of Nrf2/HO-1 axis activation. The ovariectomized mice model further demonstrated that CIN treatment ameliorated oxidative stress in vivo, partially reversing OVX-induced bone loss. This improvement was seen in the trabecular microarchitecture and bone biochemical indices. However, when ML385 was concurrently injected with CIN, the positive effects of CIN were largely blocked. In conclusion, this study sheds light on the intrinsic mechanisms by which CIN regulates BMSCs and highlights the potential therapeutic applications of these findings in the treatment of osteoporosis.

Helix-Induced Asymmetric Self-Assembly of π-Conjugated Block Copolymers: From Controlled Syntheses to Distinct Properties.

Conspectusπ-Conjugated polymers have gained significant interest because of their potential applications in optoelectronics, bioelectronics, and other domains. The controlled synthesis of π-conjugated block polymers optimizes their performance and enables novel properties and functions. However, precise control of the self-assembled architectures of π-conjugated polymers remains a formidable challenge. Inspired by the precise helical architectures of biomacromolecules, the helical polymers and the supramolecular helical assemblies have gained significant attention. Helical polymers with an excess of one-handed helicity can be optically active with a strong tendency toward self-assembly. Incorporating a helical polymer into a π-conjugated polymer can induce asymmetric helical assemblies, leading to novel chiral materials with unique functionalities.To control the self-assembly of architectures, π-conjugated polymers are usually synthesized into block copolymers by incorporating a polymer with self-assembling characteristics. Although various π-conjugated block copolymers have been produced, precise and asymmetric self-assembly is still challenging and has rarely been addressed. Incorporating helical polymers into the π-conjugated polymers can induce a precise and asymmetric self-assembly, which transfers the chirality of the helical polymer block to the π-conjugated polymer, resulting in chiral supramolecular architectures with unique chiroptical properties and functionalities. However, synthesizing hybrid block copolymers containing two distinct polymer blocks is complicated. Some general strategies such as connecting the chain ends of two preformed homopolymers and extending the chain of a prefabricated π-conjugated polymer with a second monomer are time-consuming and require complex synthetic protocols. Therefore, developing novel strategies for the facile synthesis of π-conjugated block copolymers with a predictable molar mass, low dispersity, and tunable composition is of practical importance.Recently, we investigated a controlled synthesis of helical polyisocyanides, helical polyallenes, and helical polycarbenes by developing advanced Pd(II) and Ni(II) catalysts. These helical polymers were successfully incorporated into π-conjugated polymers, including polythiophene, polyfluorene, and poly(phenyleneethynylene), via a one-pot sequential living block polymerization of the two distinct monomers using Pd(II)- or Ni(II)-complexes as catalysts. As a result, a variety of well-defined π-conjugated block copolymers containing helical polymeric blocks were readily synthesized. Although the copolymerized monomers possess different structures and polymerization mechanisms, the one-pot block copolymerization followed a living polymerization mechanism and provided the desired π-conjugated block copolymers in high yields with controlled molar mass, narrow size distribution, and tunable composition.Remarkably, the helical polymeric block induces the π-conjugated block copolymer asymmetric self-assembly into a supramolecular, one-handed helical architecture resulting in distinct optical properties. More interestingly, by utilizing the crystallization of conjugated blocks and one-handed helical blocks, the crystallization-driven and helix-induced precise asymmetric living self-assembly yielded a family of uniform and single-handed helical architectures with controlled dimensions, narrow distribution, and well-defined helicity. The transfer of helical chirality to the supramolecular architectures rendered the achiral π-conjugated blocks with unique chiroptical properties such as the emission of white light over a broad optical spectrum and the circularly polarized luminescence.

Controlled synthesis of cyclic helical polyisocyanides and bottlebrush polymers using a cyclic alkyne-Pd(II) catalyst.

Cyclic polymers have very unique structure and properties, and thus have drawn intense research attention. However, controlled synthesis of cyclic polymers with predictable molar mass and narrow distribution is still a challenging task. In this study, we developed a novel cyclic catalyst that initiates the ring-expansion polymerisation of isocyanides, producing a series of cyclic helical polymers with predictable molecular weight and low dispersity. Interestingly, the ring-expansion polymerization of the isocyanide macromonomers gives well-defined cyclic bottlebrush polymers. The cyclic topology was demonstrated using transmission electron microscopy.

[Mechanism of nuclear protein 1 in the resistance to axitinib in clear cell renal cell carcinoma].

OBJECTIVE: To explore the potential mechanism of resistance to axitinib in clear cell renal cell carcinoma (ccRCC), with a view to expanding the understanding of axitinib resistance, facilitating the design of more specific treatment options, and improving the treatment effectiveness and survival prognosis of patients. METHODS: By exploring the half maximum inhibitory concentration (IC50) of axitinib on ccRCC cell lines 786-O and Caki-1, cell lines resistant to axitinib were constructed by repeatedly stimulated with axitinib at this concentration for 30 cycles in vitro. Cell lines that were not treated by axitinib were sensitive cell lines. The phenotypic differences of cell proliferation and apoptosis levels between drug resistant and sensitive lines were tested. Genes that might be involved in the drug resistance process were screened from the differentially expressed genes that were co-upregulated in the two drug resistant lines by transcriptome sequencing. The expression level of the target gene in the drug resistant lines was verified by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). The expression differences of the target gene in ccRCC tumor tissues and adjacent tissues were analyzed in the Gene Expression Profiling Interactive Analysis (GEPIA) public database, and the impact of the target gene on the prognosis of ccRCC patients was analyzed in the Kaplan-Meier Plotter (K-M Plotter) database. After knocking down the target gene in the drug resistant lines using RNA interference by lentivirus vector, the phenotypic differences of the cell lines were tested again. WB was used to detect the levels of apoptosis-related proteins in the different treated cell lines to find molecular pathways that might lead to drug resistance. RESULTS: Cell lines 786-O-R and Caki-1-R resistant to axitinib were successfully constructed in vitro, and their IC50 were significantly higher than those of the sensitive cell lines (10.99 µmol/L, P < 0.01; 11.96 µmol/L, P < 0.01, respectively). Cell counting kit-8 (CCK-8) assay, colony formation, and 5-ethynyl-2 '-deoxyuridine (EdU) assay showed that compared with the sensitive lines, the proliferative ability of the resistant lines decreased, but apoptosis staining showed a significant decrease in the level of cell apoptosis of the resistant lines (P < 0.01). Although resistant to axitinib, the resistant lines had no obvious new replicated cells in the environment of 20 µmol/L axitinib. Nuclear protein 1 (NUPR1) gene was screened by transcriptome sequencing, and its RNA (P < 0.0001) and protein expression levels significantly increased in the resistant lines. Database analysis showed that NUPR1 was significantly overexpressed in ccRCC tumor tissue (P < 0.05); the ccRCC patients with higher expression ofNUPR1had a worse survival prognosis (P < 0.001). Apoptosis staining results showed that knockdown ofNUPR1inhibited the anti-apoptotic ability of the resistant lines to axitinib (786-O, P < 0.01; Caki-1, P < 0.05). WB results showed that knocking downNUPR1decreased the protein level of B-cell lymphoma-2 (BCL2), increased the protein level of BCL2-associated X protein (BAX), decreased the protein level of pro-caspase3, and increased the level of cleaved-caspase3 in the resistant lines after being treated with axitinib. CONCLUSION: ccRCC cell lines reduce apoptosis through theNUPR1 -BAX/ BCL2 -caspase3 pathway, which is involved in the process of resistance to axitinib.

Clinical observations in treatment of lower extremity varicose veins with trigger points acupuncture.

OBJECTIVES: To observe the effect of the acupuncture of myofascial trigger points (MTrPs) in the treatment of lower extremity varicose veins (LEVVs). METHODS: Overall, 260 patients with LEVVs participated in this study. LEVVs were selected based on diagnostic criteria of Clinical, Etiology, Anatomy, and Pathophysiology levels 2-5 and classified into six types on the basis of their anatomical positions. The MTrPs in the lower extremities were localized in accordance with the classification of LEVVs and treated by MTrPs acupuncture combined with self-massage and self-stretching. The interval between each treatment was 2 weeks to 1 month, depending on needling pain tolerance of each patient. An in-house evaluation was used to estimate the proportion of varicose veins in the lower limbs and their accompanying symptoms. The treatment effect was evaluated before each treatment and at 1-year follow-up. RESULTS: The mean evaluation score of LEVVs before the treatment course was 3.66 ± 1.19. After the course, this reduced to 1.18 ± 0.97, with the following response rates: 85% for excellent and good and 15% for medium. After 1-year follow-up, the mean evaluation score of all patients was 1.11 ± 0.92, with the following response rates: 87% for excellent and good, and 13% for medium. CONCLUSIONS: In some patients, MTrP acupuncture could cure LEVVs and its accompanying symptoms. These LEVVs are probably caused by fascia tension as a pre-pathology induced by the MTrPs.

Diagnostic performance of GenBody COVID-19 rapid antigen test for laboratory and non-laboratory medical professionals in real practice: A retrospective study.

Point-of-care tests for coronavirus disease 2019 (COVID-19) antigen detection have been widely used for rapid diagnosis in various settings. However, research on the diagnostic performance of the COVID-19 antigen test performed by non-laboratory personnel is limited. In this study, we aimed to elucidate the diagnostic performance of GenBody COVID-19 rapid antigen between laboratory professionals and non-laboratory staff. We retrospectively analyzed the data of patients who underwent both GenBody COVID-19 rapid antigen testing and reverse transcription polymerase chain reaction (RT-PCR) between November 01, 2021, and June 30, 2022. The diagnostic performance of the antigen test was compared between laboratory and non-laboratory operators, using RT-PCR as the gold standard. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, positive predictive value, negative predictive value, and accuracy were calculated and sensitivity analysis was performed based on the PCR cycle threshold (Ct) value. Of the 11,963 patients, 1273 (10.6%) tested positive using real-time RT-PCR. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, positive predictive value, negative predictive value, and accuracy of the GenBody COVID-19 rapid antigen test with 95% confidence interval were 79.92% (77.26%-82.39%), 99.23% (98.73%-99.57%), 103.25 (62.31-171.11), 0.2 (0.18-0.23), 510.18 (299.81-868.18), 98.11% (96.91%-98.85%), 90.75% (89.64%-91.75%) and 92.76% (91.76%-93.67%), respectively, for non-laboratory staff and 79.80% (74.78%-84.22%), 99.99% (99.94%-100.00%), 6983.92 (983.03-49617.00), 0.2 (0.16-0.25), 34566.45 (4770.30-250474.46) 99.58% (97.09%-99.94%), 99.32% (99.15%-99.46%), and 99.33% (99.13%-99.48%), respectively, for laboratory staff. Notably, when the PCR Ct value exceeded 25, the sensitivity of both the groups decreased to < 40%. The diagnostic performance of GenBody COVID-19 rapid antigen performed by non-laboratory staff was comparable to that of laboratory professionals. However, it should be noted that the sensitivity of the antigen tests decreased when the PCR Ct value exceeded 25. Overall, the GenBody COVID-19 antigen test is a viable option for non-laboratory staff during an epidemic.

Erratum: miR-199a-3p/5p regulate tumorgenesis via targeting Rheb in non-small cell lung cancer: Erratum.

[This corrects the article DOI: 10.7150/ijbs.70312.].