Nitric oxide mediates red light-induced perylenequinone production in Shiraia mycelium culture.

Perylenequinones (PQs) from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy. However, the lower yield of PQ production in mycelium cultures is an important bottleneck for their clinical application. Light has long been recognized as a pivotal regulatory signal for fungal secondary metabolite biosynthesis. In this study, we explored the role of nitric oxide (NO) in the growth and PQ biosynthesis in mycelium cultures of Shiraia sp. S9 exposed to red light. The continuous irradiation with red light (627 nm, 200 lx) suppressed fungal conidiation, promoted hyphal branching, and elicited a notable increase in PQ accumulation. Red light exposure induced NO generation, peaking to 81.7 µmol/g FW on day 8 of the culture, with the involvement of nitric oxide synthase (NOS)- or nitrate reductase (NR)-dependent pathways. The application of a NO donor sodium nitroprusside (SNP) restored conidiation of Shiraia sp. S9 under red light and stimulated PQ production, which was mitigated upon the introduction of NO scavenger carboxy-PTIO or soluble guanylate cyclase inhibitor NS-2028. These results showed that red light-induced NO, as a signaling molecule, was involved in the regulation of growth and PQ production in Shiraia sp. S9 through the NO-cGMP-PKG signaling pathway. While mycelial H2O2 content exhibited no significant alternations, a transient increase of intracellular Ca2+ and extracellular ATP (eATP) content was detected upon exposure to red light. The generation of NO was found to be interdependent on cytosolic Ca2+ and eATP concentration. These signal molecules cooperated synergistically to enhance membrane permeability and elevate the transcript levels of PQ biosynthetic genes in Shiraia sp. S9. Notably, the combined treatment of red light with 5 µM SNP yielded a synergistic effect, resulting in a substantially higher level of hypocrellin A (HA, 254 mg/L), about 3.0-fold over the dark control. Our findings provide valuable insights into the regulation of NO on fungal secondary metabolite biosynthesis and present a promising strategy involving the combined elicitation with SNP for enhanced production of photoactive PQs and other valuable secondary metabolites in fungi.

Dual-Functional Injectable Hydrogel for Osteoarthritis Treatments.

Osteoarthritis (OA) is a prevalent, chronic degenerative disease that affects people worldwide. It is characterized by the destruction of cartilage and inflammatory reactions. High levels of reactive oxygen species (ROS) cause oxidative stress, which damages lipids, proteins, and DNA, leading to cell damage and death. Furthermore, ROS also induces the production of inflammatory cytokines and cell chemotaxis, further worsening the inflammatory response and damaging cartilage resulted in limited movement. Herein, this work reports a dual-functional injectable hydrogel, which can help inhibit inflammation by scavenging ROS and provide lubrication to reduce wear and tear on the joints. To create the hydrogel, 3-aminophenylboronic acid modified hyaluronic acid is synthesized, then which is crosslinked with hydroxyl-containing polyvinyl alcohol (PVA) to construct a dual dynamic covalent crosslinked hydrogel oHA-PBA-PVA gel, Gel (HPP). The hydrogel mentioned here possesses a unique bond structure that allows it to be injected, self-heal, and provide lubrication. This innovative approach offers a new possibility for treating osteoarthritis by combining anti-inflammatory and lubrication effects.

Bamboo polysaccharides elicit hypocrellin A biosynthesis of a bambusicolous fungus Shiraia sp. S9.

Hypocrellin A (HA), a fungal perylenequinone from bambusicolous Shiraia species, is a newly developed photosensitizer for photodynamic therapy in cancer and other infectious diseases. The lower yield of HA is an important bottleneck for its biomedical application. This study is the first report of the enhancement of HA production in mycelium culture of Shiraia sp. S9 by the polysaccharides from its host bamboo which serve as a strong elicitor. A purified bamboo polysaccharide (BPSE) with an average molecular weight of 34.2 kDa was found to be the most effective elicitor to enhance fungal HA production and characterized as a polysaccharide fraction mainly composed of arabinose and galactose (53.7: 36.9). When BPSE was added to the culture at 10 mg/L on day 3, the highest HA production of 422.8 mg/L was achieved on day 8, which was about 4.0-fold of the control. BPSE changed the gene expressions mainly responsible for central carbon metabolism and the cellular oxidative stress. The induced generation of H2O2 and nitric oxide was found to be involved in both the permeabilization of cell membrane and HA biosynthesis, leading to enhancements in both intra- and extracellular HA production. Our results indicated the roles of plant polysaccharides in host-fungal interactions and provided a new elicitation technique to improve fungal perylenequinone production in mycelium cultures.

SEMA3B-AS1 suppresses colorectal carcinoma progression by inhibiting Semaphorin 3B-dependent VEGF signaling pathway activation.

Mounting evidence has demonstrated the considerable regulatory effects of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of various carcinomas. LncRNA Semaphorin 3B (SEMA3B) antisense RNA 1 (SEMA3B-AS1) has been found to be dysregulated in a few carcinomas recently. However, its potential function and mechanism in colorectal carcinoma (CRC) have not yet been examined. Here we show that SEMA3B-AS1 acts as a crucial regulator of CRC progression. We found that SEMA3B-AS1 expression was downregulated in CRC cell lines and tissues. Downregulation of SEMA3B-AS1 was significantly associated with poor survival in CRC patients. Overexpression of SEMA3B-AS1 reduced the cell growth and metastasis of CRC in vivo and in vitro. In addition, SEMA3B-AS1 promoted the expression of its sense-cognate gene SEMA3B, a member of the Semaphorin family (SEMAs), by recruiting EP300 to induce H3K9 acetylation at the SEMA3B promoter. Furthermore, we proved that SEMA3B-AS1 suppressed CRC angiogenesis by affecting the vascular endothelial growth factor signaling pathway activation which was regulated by the SEMA3B-NRP1 axis. Our work unravels a novel mechanism of SEMA3B-AS1 in the inhibition of CRC malignant progression and highlights its probability as a new promising diagnostic marker and therapeutic target for CRC interventions.

Peripheral BDNF Regulates Somatosensory-Sympathetic Coupling in Brachial Plexus Avulsion-Induced Neuropathic Pain.

Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.

Effects of branched-chain amino acids on Shiraia perylenequinone production in mycelium cultures.

BACKGROUND: Perylenequinones from Shiraia fruiting bodies are excellent photosensitizers and widely used for anti-cancer photodynamic therapy (PDT). The lower yield of Shiraia perylenequinones becomes a significant bottleneck for their medical application. Branched-chain amino acids (BCAAs) not only serve as important precursors for protein synthesis, but also are involved in signaling pathway in cell growth and development. However, there are few reports concerning their regulation of fungal secondary metabolism. In present study, the eliciting effects of BCAAs including L-isoleucine (L-Ile), L-leucine (L-Leu) and L-valine (L-Val) on Shiraia perylenequinone production were investigated. RESULTS: Based on the analysis of the transcriptome and amino acid contents of Shiraia in the production medium, we revealed the involvement of BCAAs in perylenequinone biosynthesis. The fungal conidiation was promoted by L-Val treatment at 1.5 g/L, but inhibited by L-Leu. The spore germination was promoted by both. The production of fungal perylenequinones including hypocrellins A (HA), HC and elsinochromes A-C (EA-EC) was stimulated significantly by L-Val at 1.5 g/L, but sharply suppressed by L-Leu. After L-Val treatment (1.5 g/L) in Shiraia mycelium cultures, HA, one of the main bioactive perylenequinones reached highest production 237.92 mg/L, about 2.12-fold than that of the control. Simultaneously, we found that the expression levels of key genes involved in the central carbon metabolism and in the late steps for perylenequinone biosynthesis were up-regulated significantly by L-Val, but most of them were down-regulated by L-Leu. CONCLUSIONS: Our transcriptome analysis demonstrated that BCAA metabolism was involved in Shiraia perylenequinone biosynthesis. Exogenous BCAAs exhibit contrasting effects on Shiraia growth and perylenequinones production. L-Val could promote perylenequinone biosynthesis via not only enhancing the central carbon metabolism for more precursors, but also eliciting perylenequinone biosynthetic gene expressions. This is the first report on the regulation of BCAAs on fungal perylenequinone production. These findings provided a basis for understanding physiological roles of BCAAs and a new avenue for increasing perylenequinone production in Shiraia mycelium cultures.

Brachial plexus avulsion induced changes in gut microbiota promotes pain related anxiety-like behavior in mice.

Introduction: Brachial plexus avulsion (BPA) injury develops frequent and intense neuropathic pain, involving in both peripheral and central nervous systems. The incidence of anxiety or depression caused by BPA-induced neuropathic pain is high, but the underlying mechanism remains unclear. Methods: We established a BPA mice model and assessed its negative emotions through behavioral tests. To further explore the role of the microbiota-gut-brain axis in the unique emotional behavior after BPA, we performed intestinal fecal 16s and metabolomics assays. Psychobiotics (PB) supplementation was administered to BPA mice to check the probiotics effects on BPA-induced anxiety behaviors. Results: Pain related anxiety-like behavior was observed at the early stage after BPA (7 days), while no depression-like behavior was detected. Intriguingly, gut microbiota diversity was increased in BPA mice, and the most abundant probiotics, Lactobacillus, showed obvious changes. Lactobacillus_reuteri was significantly decreased in BPA mice. Metabolomics analysis showed that Lactobacillus_reuteri-related bile acid pathway and some neurotransmitter amino acids were significantly altered. Further PB (dominated by Lactobacillus_reuteri) supplementation could significantly relieve BPA-induced anxiety-like behaviors in mice. Conclusion: Our study suggests that pathological neuralgia after BPA could alter intestinal microbiota diversity, especially Lactobacillus, and the changes in neurotransmitter amino acid metabolites may be the key reason for the onset of anxiety-like behaviors in BPA mice.

Case report: A rare case of massive peripheral nerve melanotic schwannoma and review of the literature.

Melanotic schwannoma is a rare tumor with indeterminate biologic behavior and varying treatment recommendations. Just about 200 cases have been reported worldwide, in which occurred in peripheral nerves has even less reported. Due to the lack of cognition of melanotic schwannoma, it is easy to be misdiagnosed and mistreatment in primary hospitals. Herein, we presented a case of massive melanotic schwannoma growing in the brachial plexus of an elderly male patient. First, the patient underwent a left forearm tumor resection in the local primary hospital because a painless lump was found there in 2017, of which details remain unclear. After this operation, the patient developed the symptoms of left median nerve injury. Thus, he came to our hospital and underwent a second operation. During this operation, we found that a part of the median nerve was absent at the left forearm, and the remanent median nerve, from the broken end to the elbow, was totally turned black, which was accompanied by petroleum-like exudate. Losing the opportunity for nerve repair, the black nerve was removed extensively and thoroughly. Postoperative pathological diagnosis revealed that the tumor was melanotic schwannoma. Then 4 years later, the tumor recurrence again, which led to the paralysis of the whole left arm and severe nerve pain, and the pulmonary metastasis of the tumor was detected at the same time. The black nerve was resected again in our hospital, and the nerve pain was partially relieved after the operation. To the best of our knowledge, it is the first time to report a melanotic schwannoma case that happened in the peripheral nerve trunk and then spread to the whole brachial plexus. There were many questions that worthy of discussion could be invited from this case, and we analyzed and discussed them based on the relevant literature. In conclusion, we reported a rare case of melanotic schwannoma that happened in the brachial plexus and illustrated the problems of the diagnosis and treatment of it based on the analysis of the relevant literature, which is helpful for the cognition of this rare nerve tumor.

PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products.

Osteoblast apoptosis plays an important role in age-related bone loss and osteoporosis. Our previous study revealed that advanced oxidation protein products (AOPPs) could induce nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) production, cause mitochondrial membrane potential (ΔΨm) depolarization, trigger the mitochondria-dependent intrinsic apoptosis pathway, and lead to osteoblast apoptosis and ultimately osteopenia and bone microstructural destruction. In this study, we found that AOPPs also induced mitochondrial ROS (mtROS) generation in osteoblastic MC3T3-E1 cells, which was closely related to NOX-derived ROS, and aggravated the oxidative stress condition, thereby further promoting apoptosis. Removing excessive ROS and damaged mitochondria is the key factor in reversing AOPP-induced apoptosis. Here, by in vitro studies, we showed that rapamycin further activated PINK1/Parkin-mediated mitophagy in AOPP-stimulated MC3T3-E1 cells and significantly alleviated AOPP-induced cell apoptosis by eliminating ROS and damaged mitochondria. Our in vivo studies revealed that PINK1/Parkin-mediated mitophagy could decrease the plasma AOPP concentration and inhibit AOPP-induced osteoblast apoptosis, thus ameliorating AOPP accumulation-related bone loss, bone microstructural destruction and bone mineral density (BMD) loss. Together, our study indicated that therapeutic strategies aimed at upregulating osteoblast mitophagy and preserving mitochondrial function might have potential for treating age-related osteoporosis.

Clinical outcomes of a novel porcine small intestinal submucosa patch for full-thickness hand skin defects: a retrospective investigation.

OBJECTIVE: To investigate the clinical outcomes of a novel soft tissue repair patch (porcine small intestinal submucosa patch, SIS patch) in the treatment of full-thickness hand skin defects. METHODS: From January 2017 to July 2019, 80 patients with hand soft tissue defects, who met the inclusion criteria, were retrospectively reviewed and divided into two groups. After debridement, patients in group A were treated with the novel SIS patch to cover the wound, and patients in group B were treated with autologous skin graft. The dimensions of skin defect area and healing outcome were evaluated and recorded. Scar assessment was carried out using Scar Cosmesis Assessment and Rating Scale (SCAR scale) at the last follow-up postoperation, and the recovery of wound sensation was assessed at the same time using British Medical Research Council (BMRC) grading of sensorimotor recovery. All the data were collected and statistically analyzed. RESULTS: A total of 80 patients were enrolled in the study with 40 patients in each group. Four patients in group A and 5 patients in group B were excluded due to wound infection and lost to follow-up. There were 36 patients in group A and 35 patients in group B finally got follow-up postoperation with mean interval of 12.75 ± 5.61 months in group A and 14.11 ± 5.42 months in group B. The dimensions of skin defect area in group A ranged from 7.5 to 87.5 cm2 (mean 25.97 ± 18.66 cm2) and in group B ranged from 7.5 to 86.25 cm2 (mean 33.61 ± 19.27 cm2) which have no significant difference (P > 0.05). SCAR scale results of group A and group B were 10.98 ± 0.33 and 9.49 ± 0.35, respectively, and the difference was statistically significant (P < 0.05). BMRC grading results showed 6 cases of S4, 11 cases of S3+, 5 cases of S3, 6 cases of S2, 6 cases of S1 and 2 cases of S0 in group A, and 8 cases of S4, 10 cases of S3+, 7 cases of S3, 4 cases of S2, 5 cases of S1, and 1 case of S0 in group B, which had no significant difference between them (P > 0.05). CONCLUSIONS: The novel SIS patch is an applicable biological material in the treatment of hand skin defect, which could achieve a better cosmetic appearance of the newborn skin tissue.

Evolutionary trends in human mandibles and dentition from Neolithic to current Chinese.

OBJECTIVES: This study aimed to systematically compare Neolithic mandibles and dentition with modern Chinese, and thereby discern human evolutionary trends. MATERIALS AND METHODS: Neolithic remains of 45 adults unearthed at the Zhangqiu Jiaojia site, were compared with clinical records of 48 patients at Shandong University. All samples were scanned by cone beam computed tomography (CBCT) using identical parameters. Digital imaging and communications in medicine images were collected, three-dimensional models reconstructed, and morphology measurements obtained using Mimics software. RESULTS: Neolithic mandibles were significantly larger in their vertical and sagittal dimensions (P < .05), but similar in horizontal width to modern humans. Their condyles had fewer bird beak and crooked finger shaped morphologies than modern mandibles (P < .05). Neolithic third molars were more often erupted than in modern mandibles, and their Position A, class I and II, and vertical impactions were more common (P < .05). Neolithic teeth were generally smaller in crown lengths and in cross-sectional areas, than their modern counterparts (P < .05). CONCLUSIONS: Neolithic mandibles were larger than modern humans, who have refined diets and mandibular atrophy. They had fewer abnormally shaped condylar morphologies, and much fewer third molar impactions than in modern humans. However, modern dentition particularly their crowns are larger, likely through genetic influx from migrations.

Prediction Model of Sound Signal in High-Speed Milling of Wood-Plastic Composites.

The accuracy of the acoustic signal prediction model for wood-plastic composites milling has an important influence on the condition monitoring of the cutting process and the improvement of the machining environment. To establish a high-precision prediction model of sound signal in the high-speed milling of wood-plastic composites, high-speed milling experiments on self-developed wood-plastic composites were carried out with cemented carbide tools. A mathematical model of the relationship of the four milling parameters, including axial cutting depth, radial cutting depth, feed rate and cutting speed, and the sound signal of wood-plastic composites milling, was established by using the full-factor test method. The experimental data obtained by the orthogonal test method were used as the test samples in the mathematical model. Test results show that the prediction accuracy of the mathematical model of the sound signal in the milling of wood-plastic composites exceeds 95.4%. To further improve the prediction accuracy of the sound signal in the milling of wood-plastic composites, a prediction model was established using back propagation (BP) neural network. Then, the particle swarm optimization (PSO) algorithm was used to optimize the BP neural network, obtaining the PSO-BP neural network prediction model. The test results show that the prediction accuracy of the PSO-BP prediction model for the sound signal in the high-speed milling of wood-plastic composites exceeds 97.5%. The PSO-BP model has a better global approximation ability and higher prediction accuracy than the BP model. The research results can provide a reference basis for sound signal prediction in the high-speed milling of wood-plastic composites.

Research Progress of Noise in High-Speed Cutting Machining.

High-speed cutting technology has become a development trend in the material processing industry. However, high-intensity noise generated during high-speed cutting exerts a potential effect on the processing efficiency, processing accuracy, and product quality of the workpiece; it may even cause hidden safety hazards. To conduct an in-depth study of noise in high-speed cutting machining, this work reviews noise sources, noise collection and numerical recognition, noise control, and condition monitoring based on acoustic signals. First, this article introduces noise sources, noise signal acquisition equipment, and analysis software. It is pointed out that how to accurately classify and recognize the target signal in the complex high-speed machining environment is one of the focuses of scholars' research. Then, it points out that a computer achieves high accuracy and practicability in signal analysis, processing, and result display. Second, in the aspect of noise signal processing, the characteristics of noise signals are analyzed. It is pointed out that accurately analyzing the characteristics of different noise source signals and adopting appropriate methods for identification and processing are the necessary conditions for effectively controlling and reducing the noise in the process of high-speed cutting. The advantages and applicable fields of artificial intelligence algorithms in processing mixed noise source signals with different frequency characteristics are compared, providing ideas for studying the mechanism of noise generation and the identification of noise sources. Third, in terms of noise control, a detailed overview is provided from the aspects of the treatment of the noise source that contributes the most to the overall noise, the improvement of the tool structure, the optimization of cutting parameters, and the analysis of contact factors between the tool and the workpiece. It provides an effective way for noise control in the process of high-speed cutting. In addition, the application of acoustic signals to condition monitoring is also thoroughly analyzed. The practical application value of condition monitoring based on acoustic signals in high-speed machining is highlighted. Finally, this paper summarizes the positive significance of noise research in high-speed machining and identifies key problems and possible research methods that require further study in the future.

Oreocharisqianyuensis, a new species of Gesneriaceae from Southwest, China based on morphological and molecular evidence.

Oreocharisqianyuensis, a new species of Gesneriaceae from Southwest, China, is described and illustrated based on morphological comparisons and molecular phylogenetic analyses. Phylotranscriptomic analyses of the new species in the context of a comprehensive phylogeny with dense sampling of 88% (111/126) of all species of the genus indicated that the new species was most closely-related to O.fargesii. The new species is morphologically similar to O.fargesii and O.nanchuanica in the shape, color and structure of flowers and the number of stamens, but differs in the leaf blade shape, margin and the indumentum characters of the inflorescence. Its morphological relationship with similar species is discussed, the detailed descriptions, colour photographs, distribution, as well as the IUCN threatened status based on the IUCN Red List Categories and Criteria are also provided.

Petrocosmeaduyunensis (Gesneriaceae), a new species from Guizhou, China.

Plants belonging to the genus Petrocosmea are rare and small herbs difficult to find in the wild. In the present study, a new species, Petrocosmeaduyunensis, from Guizhou, China, is described. The species is most similar to P.leiandra and differs from it by a distinctly recurved abaxial corolla lip, free anthers and included pistil. Detailed morphological comparisons are given. One population with about 100 mature individuals was found at the type locality. This new taxon was assessed as "Data Deficient" (DD) according to the IUCN standards.

STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis.

Lactate dehydrogenase A (LDHA), a critical component of the glycolytic pathway, relates to the development of various cancers, including thyroid cancer. However, the regulatory mechanism of LDHA inhibition and the physiological significance of the LDHA inhibitors in papillary thyroid cancer (PTC) are unknown. Long non-coding RNA (lncRNA) plays a vital role in tumor growth and progression. Here, we identified a novel lncRNA LINC00671 negatively correlated with LDHA, downregulating LDHA expression and predicting good clinical outcome in thyroid cancer. Moreover, hypoxia inhibits LINC00671 expression and activates LDHA expression largely through transcriptional factor STAT3. STAT3/LINC00671/LDHA axis regulates thyroid cancer glycolysis, growth, and lung metastasis both in vitro and in vivo. In thyroid cancer patients, LINC00671 expression is negatively correlated with LDHA and STAT3 expression. Our work established STAT3/LINC00671/LDHA as a critical axis to regulate PTC growth and progression. Inhibition of LDHA or STAT3 or supplement of LINC00671 could be potential therapeutic strategies in thyroid cancer.

LSD1-Demethylated LINC01134 Confers Oxaliplatin Resistance Through SP1-Induced p62 Transcription in HCC.

BACKGROUND AND AIMS: Oxaliplatin (OXA) is one of the most common chemotherapeutics in advanced hepatocellular carcinoma (HCC), the resistance of which poses a big challenge. Long noncoding RNAs (lncRNAs) play vital roles in chemoresistance. Therefore, elucidating the underlying mechanisms and identifying predictive lncRNAs for OXA resistance is needed urgently. METHODS: RNA sequencing (RNA-seq) and fluorescence in situ hybridization (FISH) were used to investigate the OXA-resistant (OXA-R) lncRNAs. Survival analysis was performed to determine the clinical significance of homo sapiens long intergenic non-protein-coding RNA 1134 (LINC01134) and p62 expression. Luciferase, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and chromatin isolation by RNA purification (ChIRP) assays were used to explore the mechanisms by which LINC01134 regulates p62 expression. The effects of LINC01134/SP1/p62 axis on OXA resistance were evaluated using cell viability, apoptosis, and mitochondrial function and morphology analysis. Xenografts were used to estimate the in vivo regulation of OXA resistance by LINC01134/SP1/p62 axis. ChIP, cell viability, and xenograft assays were used to identify the demethylase for LINC01134 up-regulation in OXA resistance. RESULTS: LINC01134 was identified as one of the most up-regulated lncRNAs in OXA-R cells. Higher LINC01134 expression predicted poorer OXA therapeutic efficacy. LINC01134 activates anti-oxidative pathway through p62 by recruiting transcription factor SP1 to the p62 promoter. The LINC01134/SP1/p62 axis regulates OXA resistance by altering cell viability, apoptosis, and mitochondrial homeostasis both in vitro and in vivo. Furthermore, the demethylase, lysine specific demethylase 1 (LSD1) was responsible for LINC01134 up-regulation in OXA-R cells. In patients with HCC, LINC01134 expression was positively correlated with p62 and LSD1 expressions, whereas SP1 expression positively correlated with p62 expression. CONCLUSIONS: LSD1/LINC01134/SP1/p62 axis is critical for OXA resistance in HCC. Evaluating LINC01134 expression in HCC will be effective in predicting OXA efficacy. In treatment-naive patients, targeting the LINC01134/SP1/p62 axis may be a promising strategy to overcome OXA chemoresistance.

Effects of preoperative serum vitamin D levels on early clinical function outcomes and the moderate-to-severe pain prevalence in postmenopausal women after primary total knee arthroplasty.

OBJECTIVE: To investigate the impact of vitamin D levels on early clinical function outcomes and the potential risk factors of moderate-to-severe pain prevalence in postmenopausal women after primary total knee arthroplasty (TKA). METHODS: From April 2017 to December 2019, 226 women were retrospectively recruited. The women were divided into two groups based on their preoperative serum 25-hydroxyvitamin D levels: (1) vitamin D-sufficient group (≥30 ng/mL); (2) vitamin D-deficient group (<30 ng/mL). The visual analog scale, Western Ontario and McMaster Arthritis Index score, and Knee Society Score were used to evaluate clinical outcomes. Risk factors for developing postoperative moderate-to-severe knee pain were studied using multivariate binary logistic regression analyses. RESULTS: There was no significant difference in preoperative clinical function assessment between the two groups. The difference in postoperative Western Ontario and McMaster Arthritis Index score between the two groups was statistically significant (15.3 ±â€Š0.7 vs 15.6 ±â€Š0.7: P = 0.02). However, the differences in postoperative visual analog scale and Knee Society Score scores between the two groups were not significant (P > 0.05). The incidence of postoperative moderate-to-severe pain was 16.4% (95% CI 11.8%-21.9%). Multivariate logistic regression analysis revealed that vitamin D deficiency, smoking, and high body mass index were potential risk factors for moderate-to-severe knee pain in postmenopausal women early after TKA (P < 0.05). CONCLUSION: Preoperative vitamin D deficiency may adversely affect early functional outcomes in postmenopausal women after TKA. In addition, vitamin D deficiency, smoking, and high body mass index were independent risk factors for moderate-to-severe knee pain after surgery.

FOXO3A-induced LINC00926 suppresses breast tumor growth and metastasis through inhibition of PGK1-mediated Warburg effect.

Phosphoglycerate kinase 1 (PGK1), a critical component of the glycolytic pathway, relates to the development of various cancers. However, the mechanisms of PGK1 inhibition and physiological significance of PGK1 inhibitors in cancer cells are unclear. Long non-coding RNAs (lncRNAs) play a vital role in tumor growth and progression. Here, we identify a lncRNA LINC00926 that negatively regulates PGK1 expression and predicts good clinical outcome of breast cancer. LINC00926 downregulates PGK1 expression through the enhancement of PGK1 ubiquitination mediated by E3 ligase STUB1. Moreover, hypoxia inhibits LINC00926 expression and activates PGK1 expression largely through FOXO3A. FOXO3A/LINC00926/PGK1 axis regulates breast cancer glycolysis, tumor growth, and lung metastasis both in vitro and in vivo. In breast cancer patients, LINC00926 expression is negatively correlated with PGK1 and positively correlated with FOXO3A expression. Our work established FOXO3A/LINC00926/PGK1 as a critical axis to regulate breast cancer growth and progression. Targeting PGK1 or supplement of LINC00926 or FOXO3A could be potential therapeutic strategies in breast cancer.

Drug-Coated Balloon versus Bare Nitinol Stent in Femoropopliteal Artery: 12 Months Outcome from a Single Center in China.

OBJECT: The study sought to compare the safety and effectiveness of drug-coated balloon (DCB) with bare nitinol stent in patients with complex femoropopliteal(FP) lesions in real-world practice. METHODS: Patients with symptomatic (Rutherford stage 2 to 5) femoropopliteal lesions who underwent DCB or bare nitinol stent implantation at the Department of Cardiovascular Surgery of China-Japan Friendship Hospital from June 2016 to September 2017 were included. Demographics, angiographic and procedural variables were included. Freedom from target lesion revascularization (TLR), primary patency and major adverse events were obtained from follow-up results at 3,6 and12 months. Descriptive analysis was performed on all variables. RESULTS: A total of 90 eligible patients were enrolled, which included 51 DCB subjects (mean age, 63.1 ± 13.2 years; 76.5% male) with 55 lesions and 39 nitinol stent subjects (mean age, 66.5 ± 10.5 years; 61.5% male) with 42 lesions. Significant higher primary patency was observed in the DCB group compared with the stent group (74.5% vs. 52.4%; log-rank test P = 0.018; HR 0.335, 95%CI 0.124-0.903, P = 0.031). The rates of freedom from TLR (f-TLR) were 78.2% and 59.5% (log-rank test P = 0.032) for the DCB group and the stent group, respectively, at 12 months. CD-TLR rates were 18.2% vs. 38.1% with a P-value of 0.023. Female sex (HR 6.122, 95%CI 1.880-19.934, P = 0.003), lesion length over 20 cm (HR 5.514, 95%CI 2.312-13.148, P < 0.001) and renal insufficiency (HR 2.609, 95%CI 1.087-6.260, P = 0.032) were suggested as independent risk factors of reducing primary patency. There were no significant differences in major adverse events between the 2 groups. CONCLUSION: The result above demonstrates that DCB treatment has higher primary patency and lower TLR at 12 months than nitinol stent. These data confirm the safety and effectiveness of the DCB for patients with complex femoropopliteal lesions.