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Despite the recent development of improved methods of treating melanoma such as targeted therapy, immunotherapy or combined treatment, the number of new cases worldwide is increasing. It is well known that active metabolites of vitamin D3 and lumisterol (L3) exert photoprotective and antiproliferative effects on the skin, while UV radiation is a major environmental risk factor for melanoma. Thus, many natural metabolites and synthetic analogs of steroidal and secosteroidal molecules have been tested on various cancer cells and in animal models. In this study, we tested the anti-melanoma properties of several natural derivatives of vitamin D3 and L3 in comparison to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). A significant decrease in melanoma cell proliferation and cell mobility was observed for selected derivatives, with (25R)-27-hydroxyL3 showing the highest potency (lowest IC50) in A375 cells but lower potency in SK-MEL-28 cells, whereas the parent L3 failed to inhibit proliferation. The efficacy (% inhibition) by 1,24,25(OH)3D3 and 1,25(OH)2D3 were similar in both cell types. 1,25(OH)2D3 showed higher potency than 1,24,25(OH)3D3 in SK-MEL-28 cells, but lower potency in A375 cells for the inhibition of proliferation. As for 1,25(OH)2D3, but not the other derivatives tested, treatment of melanoma cells with 1,24,25(OH)3D3 markedly increased the expression of CYP24A1, enhanced translocation of the vitamin D receptor (VDR) from the cytoplasm to the nucleus and also decreased the expression of the proliferation marker Ki67. The effects of the other compounds tested were weaker and occurred only under certain conditions. Our data indicate that 1,24,25(OH)3D3, which has undergone the first step in 1,25(OH)2D3 inactivation by being hydroxylated at C24, still shows anti-melanoma properties, displaying higher potency than 1,25(OH)2D3 in SK-MEL-28 cells. Furthermore, hydroxylation increases the potency of some of the lumisterol hydroxy-derivatives, as in contrast to L3, (25R)-27(OH)L3 effectively inhibits proliferation and migration of the human malignant melanoma cell line A375. [ABSTRACT FROM AUTHOR]

Introduction: Despite the long-term use of intramuscular and intraosseous lidocaine trigger point injections (LTPI) in the treatment of patients with low back pain, there have been no studies examining their efficiency in treatment of residual pain after degenerative lumbar spinal stenosis (DLSS) decompression surgery. The purpose of our research is to examine the LTPI efficiency in the treatment of residual lumbar pain after DLSS decompression surgery and to compare the analgesic and recovery effects of intramuscular and intraosseous LTPI administered in the L4–S1 region and in the posterior superior iliac spine (PSIS) after treatment and during four months of follow-up. Materials and Methods: We observed 99 patients (F:50, M:49) aged 42 to 59 years with residual neurological disorders after DLSS decompression surgery. In all patients, the pain syndrome exceeded 6 points on the VAS and averaged 7.2 ± 0.11 points. The control group (n = 21) underwent only pharmacotherapy. In addition to pharmacotherapy, the LTPI group underwent intramuscular LTPI in L4–S1 (n = 20), intramuscular LTPI in the PSIS (n = 19), intraosseous LTPI in L5, S1 (n = 20), and intraosseous LTPI in the PSIS (n = 19). A neurological examination was carried out before treatment, 7 days after completion of treatment, and at the end of the second and fourth months of the follow-up period. Results: In the control group, intramuscular LTPI in L4–S1 subgroup, intramuscular LTPI in PSIS subgroup, intraosseous LTPI in L5, S1 subgroup, and intraosseous LTPI in PSIS subgroup, the severity of pain decreased after treatment by 27.1% (p ≤ 0.05), 41.7% (p ≤ 0.01), 50.7% (p ≤ 0.01), 69% (p ≤ 0.01), and 84.7% (p ≤ 0.01), respectively, and at the end of the second month of follow-up, by 14.3% (p > 1), 29.2% (p ≤ 0.05), 38% (p ≤ 0.01), 53.5% (p ≤ 0.01), and 72.2% (p ≤ 0.01), respectively. Reduction of neurogenic claudication, regression of sensory deficit, increase of daily step activity, and improvement of quality of life after treatment were noted in intramuscular LTPI subgroups by 19.6% (p ≤ 0.05), 36.4 (p ≤ 0.05), 40.3% (p ≤ 0.01), and 21.0% (p ≤ 0.05), respectively, and in interosseous LTPI subgroups by 48.6% (p ≤ 0.01), 67.4% (p ≤ 0.01), 68.3% (p ≤ 0.01), and 46% (p ≤ 0.01), respectively. Conclusions: LTPI is highly effective in the treatment of patients with residual pain after DLSS decompression surgery. High analgesic effect, significant regression of sensory deficits and gait disorders, and remarkable improvement of daily step activity and quality of life are noted not only after the end of LTPI treatment but also continue for at least 2 months after treatment. Intraosseous LTPI is more effective than intramuscular LTPI by 92%, and LTPI in PSIS is more effective than LTPI in L4–S1 by 28.6%. [ABSTRACT FROM AUTHOR]

In 2023, the World Obesity Atlas Federation concluded that more than 50% of the world's population would be overweight or obese within the next 12 years. At the heart of this epidemic lies the gut microbiota, a complex ecosystem that profoundly influences obesity-related metabolic health. Its multifaced role encompasses energy harvesting, inflammation, satiety signaling, gut barrier function, gut-brain communication, and adipose tissue homeostasis. Recognizing the complexities of the cross-talk between host physiology and gut microbiota is crucial for developing cutting-edge, microbiome-targeted therapies to address the global obesity crisis and its alarming health and economic repercussions. This narrative review analyzed the current state of knowledge, illuminating emerging research areas and their implications for leveraging gut microbial manipulations as therapeutic strategies to prevent and treat obesity and related disorders in humans. By elucidating the complex relationship between gut microflora and obesity, we aim to contribute to the growing body of knowledge underpinning this critical field, potentially paving the way for novel interventions to combat the worldwide obesity epidemic., Competing Interests: Compliance and ethics. The authors declare that they have no conflict of Interest., (© 2024. Science China Press.)

To better regulate the speed of diesel engines and optimize the speed overshoot and fast response, a speed control method combining the improved salp swarm algorithm (ISSA) with the proportional integral and differential (PID) controller was proposed. A real-time simulation model for a high-pressure common rail diesel engine was established. Addressing the challenges of the salp swarm algorithm (SSA), such as uneven population distribution and its tendency to become trapped in local optima, logistic-tent chaotic mapping, adaptive parameters was introduced, as well as adaptive dynamic inertia weights, elite strategy, and a dynamic inverse strategy. These enhancements bolstered the algorithm's precision and efficiency in both global and local searches. Using the enhanced SSA, the parameters of the PID controller for the diesel engine model was optimized. The results indicated that the ISSA offers superior parameter identification precision, strengthening speed control stability. During sudden changes in speed and load, the overshoot decreased by an average of more than 30.3% and more than 8.6%, respectively. Moreover, the settling time decreased by an average of more than 0.76 s and 1.52 s, respectively, significantly enhancing the quality of diesel engine speed control. [ABSTRACT FROM AUTHOR]

The maintenance of electrical grids is crucial for improving their reliability, performance, and cost-effectiveness. It involves employing various strategies to ensure smooth operation and address potential issues. With the advancement of digital technologies, utilizing time-series prediction has emerged as a valuable approach to enhance maintenance practices in electrical systems. The utilization of various recorded data from electrical grid components plays a crucial role in digitally enabled maintenance. However, the comprehensive exploration of time-series data prediction for maintenance is still lacking. This review paper extensively explores different time series that can be utilized to support maintenance efforts in electrical grids with regard to different maintenance strategies and grid components. The digitization of the electrical grids has enabled the collection of diverse time-series data from various network components. In this context, the paper provides an overview of how these time-series and historical-fault data can be utilized for maintenance purposes in electrical grids. Various maintenance levels and time series used for maintenance purposes in different components of the electrical grid are presented. [ABSTRACT FROM AUTHOR]

Malnutrition is a common problem in patients with metastatic colorectal cancer (mCRC) receiving targeted therapy plus chemotherapy, resulting in severe toxicity and decreased survival rates. This retrospective study employing propensity score matching (PSM) examined the efficacy and safety of a supplemental home parenteral nutrition (HPN) program for patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy. This retrospective nationwide registry study included data from 14 medical centers/hospitals across Taiwan, and the data period ranged from November 2016 to December 2020. Patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy as their first-line therapy were included and divided into HPN and non-HPN program groups. HPN was initiated based on patient-specific factors, such as baseline nutritional status, treatment-related toxicities, and comorbidities. Clinical outcomes were evaluated using response to therapy, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). This study recruited 758 patients, of whom 110 and 648 were included in the HPN and non-HPN program groups, respectively. After 1:3 PSM, the data of 109 and 327 patients from the HPN and non-HPN program groups were analyzed, respectively. The HPN program group had a higher metastasectomy rate (33.9% vs. 20.2%, p = 0.005), and longer duration of treatment and DoR than the non-HPN program group (13.6 vs. 10.3 and 13.6 vs. 9.9 months, p = 0.001 and < 0.001, respectively). The HPN program group tended to have a longer median PFS (18.2 vs. 13.9 months, p = 0.102). Moreover, we noted a significant improvement in the median OS in the same group (53.4 vs. 34.6 months, p = 0.002). Supplemental HPN programs may be recommended for select patients with mCRC receiving targeted therapy plus chemotherapy to improve oncological outcomes. [ABSTRACT FROM AUTHOR]

Respiratory viral infections are a leading global cause of disease with multiple viruses detected in 20–30% of cases, and several viruses simultaneously circulating. Some infections with unique viral copathogens result in reduced pathogenicity, while other viral pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic. To better understand viral–viral coinfections and predict potential mechanisms that result in distinct disease outcomes, we first systematically fit mathematical models to viral load data from ferrets infected with respiratory syncytial virus (RSV), followed by influenza A virus (IAV) after 3 days. The results suggest that IAV reduced the rate of RSV production, while RSV reduced the rate of IAV infected cell clearance. We then explored the realm of possible dynamics for scenarios that had not been examined experimentally, including a different infection order, coinfection timing, interaction mechanisms, and viral pairings. IAV coinfection with rhinovirus (RV) or SARS-CoV-2 (CoV2) was examined by using human viral load data from single infections together with murine weight-loss data from IAV-RV, RV-IAV, and IAV-CoV2 coinfections to guide the interpretation of the model results. Similar to the results with RSV-IAV coinfection, this analysis shows that the increased disease severity observed during murine IAV-RV or IAV-CoV2 coinfection was likely due to the slower clearance of IAV-infected cells by the other viruses. The improved outcome when IAV followed RV, on the other hand, could be replicated when the rate of RV infected cell clearance was reduced by IAV. Simulating viral–viral coinfections in this way provides new insights about how viral–viral interactions can regulate disease severity during coinfection and yields testable hypotheses ripe for experimental evaluation. [ABSTRACT FROM AUTHOR]

Room-temperature vulcanized rubber is an excellent polymer material with excellent electrical insulation and mechanical properties, which can be used for field insulation of high-voltage bare wire. In this paper, a room-temperature cured coating material was prepared from α,ω-dihydroxy polydimethylsiloxane (PDMS), polyurethane-modified silicone material (PU-Si), and Methyltris(methylethylketoxime) silane (MOS). The study showed that the coating made by adding PDMS (70 g), PU-Si (30 g), CaCO3 (90 g), MOS (7 g), KH792 (5 g), and Mg(OH)2 (30 g) had a surface drying time of 19.1 min, tensile strength of 3.2 Mpa, volume resistivity greater than 4 × 1014 Ω·cm, breakdown voltage greater than 20 kV/mm, and flame retardant performance of the FV-1 level. The comprehensive performance of the insulation material meets the national standard of "Aerial insulated cables for rated voltage of 10 kV" (GB/T14049-2008), while the insulation material has been successfully applied to the overhead line renovation project of the State Grid Hubei Electric Power Company (Wuhan, China). [ABSTRACT FROM AUTHOR]

Unsuccessful wound closure in chronic wounds can be linked to altered keratinocyte activation and their inability to re-epithelize. Suggested mechanisms driving this impairment involve unbalanced cytokine signaling. However, the molecular events leading to these aberrant responses are poorly understood. Among cytokines affecting keratinocyte responses, Transforming Growth Factor-β (TFG-β) is thought to have a great impact. In this study, we have used a previously characterized skin epidermal in vitro model, HaCaT cells continuously exposed to TGF-β1, to study the wound recovery capabilities of chronified/senescent keratinocytes. In this setting, chronified keratinocytes show decreased migration and reduced activation in response to injury. Amniotic membrane (AM) has been used successfully to manage unresponsive complicated wounds. In our in vitro setting, AM treatment of chronified keratinocytes re-enabled migration in the early stages of wound healing, also promoting proliferation at later stages. Interestingly, when checking the gene expression of markers known to be altered in TGF-β chronified cells and involved in cell cycle regulation, early migratory responses, senescence, and chronic inflammation, we discovered that AM treatment seemed to reset back to keratinocyte status. The analysis of the evolution of both the levels of keratinocyte activation marker cytokeratin 17 and the spatial-temporal expression pattern of the proliferation marker Ki-67 in human in vivo biopsy samples suggests that responses to AM recorded in TGF-β chronified HaCaT cells would be homologous to those of resident keratinocytes in chronic wounds. All these results provide further evidence that sustained TGF-β might play a key role in wound chronification and postulate the validity of our TGF-β chronified HaCaT in vitro model for the study of chronic wound physiology. [ABSTRACT FROM AUTHOR]

Water can be an irritant to a power transformer, as it is recognized as a major hazard to the operation of transformers. The water content of a transformer insulation system comprises the water in the transformer insulation oil and in the cellulose paper. The increase in the water content in the insulation system leads to reduced breakdown voltage, accelerated aging of the oil–paper insulation system, and the possibility of producing bubbles at high temperatures. Therefore, various techniques have been applied to measure the water content in both oil and paper insulation. This article comprehensively reviews and analyzes the methods (technically or nontechnically) that have been used to monitor the water content in transformer insulation systems. Apart from discussing the advantages and major drawbacks of these methods, the accuracy, measurement time, and cost of each technique are also elucidated in this review. This review can be extremely useful to the utility in monitoring and maintaining the good condition of transformers. Based on the reviewed methods and their challenges, a few future research directions and prospects for determining the water content in transformer insulation systems are outlined, such as utilizing artificial intelligence and enhancing current techniques. [ABSTRACT FROM AUTHOR]

Rising greenhouse gas emissions stemming from fossil fuel-driven vehicles are causing damage to the environment. To counteract this, one solution is the adoption of electric vehicles (EV) for transportation requirements. In this regard, one category of EVs that requires special attention is light electric vehicle (LEV), mainly because of their wide potential in public transportation—especially in developing countries. To realise widespread adoption of LEVs for this purpose, it is imperative to make their charging systems more robust. Consequently, the subject of LEV charging has gained considerable traction, and numerous research works have been reported on this subject in recent years. Hence, this paper aims to chronicle recent research developments on LEV charging techniques, by placing special attention on DC-DC converter topologies used in both on-board and off-board chargers. This review explores recent LEV charger DC-DC converters in literature by segregating them into isolated and non-isolated topologies. Lastly, this work explores challenges and emerging trends in LEV charging, which can potentially be explored by researchers in the future. [ABSTRACT FROM AUTHOR]

In nature, viral coinfection is as widespread as viral infection alone. Viral coinfections often cause altered viral pathogenicity, disrupted host defense, and mixed-up clinical symptoms, all of which result in more difficult diagnosis and treatment of a disease. There are three major virus–virus interactions in coinfection cases: viral interference, viral synergy, and viral noninterference. We analyzed virus–virus interactions in both aspects of viruses and hosts and elucidated their possible mechanisms. Finally, we summarized the protocol of viral coinfection studies and key points in the process of virus separation and purification. [ABSTRACT FROM AUTHOR]

A new route to single‐step and non‐covalent immobilization of proteins on graphene is exemplified with the first biosensor for nitriles based on a graphene field‐effect transistor (GFET). The biological recognition element is a fusion protein consisting of nitrile reductase QueF from Escherichia coli with an N‐terminal self‐assembling and graphene‐binding dodecapeptide. Atomic force microscopy and analysis using a quartz crystal microbalance show that both the oligopeptide and the fusion protein incorporating it form a single adlayer of monomeric enzyme on graphene. The fusion protein has a 6.3‐fold increase in binding affinity for benzyl cyanide (BnCN) versus wild‐type QueF and a 1.4‐fold increase for affinity for the enzyme's natural substrate preQ0. Density functional theory analysis of QueF's catalytic cycle with BnCN shows similar transition‐state barriers to preQ0, but differences in the formation of the initial thioimidate covalent bonding (∆G‡ = 19.0 kcal mol−1 for preQ0 vs 27.7 kcal mol−1 for BnCN) and final disassociation step (∆G = −24.3 kcal mol−1 for preQ0 vs ∆G = +4.6 kcal mol−1 for BnCN). Not only do these results offer a single‐step route to GFET modification, but they also present new opportunities in the biocatalytic synthesis of primary amines from nitriles. [ABSTRACT FROM AUTHOR]

Caligus rogercresseyi is the main ectoparasite that affects the salmon industry in Chile. The mechanisms used by the parasite to support its life strategy are of great interest for developing control strategies. Due to the critical role of insect peritrophins in host–parasite interactions and response to pest control drugs, this study aimed to identify and characterize the peritrophin-like genes present in C. rogercresseyi. Moreover, the expression of peritrophin-like genes was evaluated on parasites exposed to delousing drugs such as pyrethroids and azamethiphos. Peritrophin genes were identified by homology analysis among the sea louse transcriptome database and arthropods peritrophin-protein database obtained from GenBank and UniProt. Moreover, the gene loci in the parasite genome were located. Furthermore, peritrophin gene expression levels were evaluated by RNA-Seq analysis in sea louse developmental stages and sea lice exposed to delousing drugs deltamethrin, cypermethrin, and azamethiphos. Seven putative peritrophin-like genes were identified in C. rogercresseyi with high homology with other crustacean peritrophins. Differences in the presence of signal peptides, the number of chitin-binding domains, and the position of conserved cysteines were found. In addition, seven peritrophin-like gene sequences were identified in the C. rogercresseyi genome. Gene expression analysis revealed a stage-dependent expression profile. Notably, differential regulation of peritrophin genes in resistant and susceptible populations to delousing drugs was found. These data are the first report and characterization of peritrophin genes in the sea louse C. rogercresseyi, representing valuable knowledge to understand sea louse biology. Moreover, this study provides evidence for a deeper understanding of the molecular basis of C. rogercresseyi response to delousing drugs. [ABSTRACT FROM AUTHOR]

Global Navigation Satellite System (GNSS) radio occultation (RO) technology has been widely used in Earth atmospheric detection and has a significant impact on numerical weather prediction (NWP), climate detection, and other fields. Cosmic-2 LEO-1 (C2E1) is a well-known RO data provider; however, its observations are confined to 45°S and 45°N. Recently, the Binhu meteorological observation test satellite (BH) has provided global coverage of RO data, including refractivity, specific humidity, and temperature data. In this study, RO data from BH and C2E1 are analyzed and compared from 8 February 2022 to 17 February 2022. Employing the European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis (ERA-5) data as a reference, both BH and C2E1 RO data agree with the ERA data, with the refractivity, temperature, and specific humidity profiles reflecting the real conditions of the natural atmosphere. In addition, BH data are comparable to C2E1 data at low and middle latitudes (0–45°), and BH data at middle and high latitudes (45–90°) are of better quality than those at low and middle latitudes (0–45°). For example, without considering the errors introduced by the interpolation of the ERA-5 data for comparative analysis, the BH refractivity profiles show a mean absolute bias of 0.73 N at low and middle latitudes and only 0.23 N at middle and high latitudes, and that for BH specific humidity profiles at middle and high latitudes is 0.015 g/kg, which is only half of that at low and middle latitudes. The BH temperature and specific humidity data show promising data accuracy. Therefore, BH RO data may provide important supplementary data at higher latitudes and may improve future NWPs through assimilation. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this retrospective observational study was to evaluate perioperative and short-term oncological outcomes of robotic-assisted rectal surgery (RRS) in hospitals with a high-volume of robotic-assisted surgeries. This study enrolled patients with rectal adenocarcinoma undergoing RRS from three high-volume institutions from December 2011 to June 2020. Compared with other studies, our results revealed the equivalent or superior perioperative and short-term oncological outcomes. Hence, RRS is an effective, safe, and feasible technique for patients with rectal cancers in high-volume hospitals. The perioperative and short-term oncological outcomes of robotic-assisted rectal surgery (RRS) are unclear. This retrospective observational study enrolled patients with rectal adenocarcinoma undergoing RRS from three high-volume institutions in Taiwan. Of the 605 enrolled patients, 301 (49.75%), 176 (29.09%), and 116 (19.17%) had lower, middle, and upper rectal cancers, respectively. Low anterior resection (377, 62.31%) was the most frequent surgical procedure. Intraoperative blood transfusion was performed in 10 patients (2%). The surgery was converted to an open one for one patient (0.2%), and ten (1.7%) patients underwent reoperation. The overall complication rate was 14.5%, including 3% from anastomosis leakage. No deaths occurred during surgery and within 30 days postoperatively. The positive rates of distal resection margin and circumferential resection margin were observed in 21 (3.5%) and 30 (5.0%) patients, respectively. The 5-year overall and disease-free survival rates for patients with stage I–III rectal cancer were 91.1% and 86.3%, respectively. This is the first multi-institutional study in Taiwan with 605 patients from three high-volume hospitals. The overall surgical and oncological outcomes were equivalent or superior to those estimated in other studies. Hence, RRS is an effective and safe technique for rectal resection in high-volume hospitals. [ABSTRACT FROM AUTHOR]

Mitochondria play a central role in energy metabolism and cell survival. They often undergo structural and dynamic changes under various types of stress and impaired energy homeostasis. In addition to the intracellular movement of mitochondria, their intercellular transport is of great importance. Intercellular transfer occurs in both physiological conditions and various pathologies. It is accompanied by elimination of damage in stressed cells and the restoration of structural and functional tissue disorders caused by mitochondrial dysfunction. This review summarizes the latest data accumulated in this area and provides a general idea on the molecular mechanisms of mitochondrial intercellular transport and its role in maintaining energy homeostasis in tissues. Promising ways of studying mitochondrial transfer for targeted therapy of many diseases are discussed separately. [ABSTRACT FROM AUTHOR]

There is a good body of literature about digital-game-based language learning (DGBL), but research has mainly focused on students as game players rather than as future educators. This paper reports on a research conducted among 154 teacher candidates at a higher-education institution in Spain regarding the adoption of digital games in education. It analyzes the participants' knowledge of and attitudes toward digital games in foreign language learning. Quantitative and qualitative data were gathered through a pre/post-test, digital game presentations, and student blog posts. The research comprised five stages associated with critical thinking skills (definition, selection, demonstration, discussion, and reflection), including a game learning module. In the first two stages, preservice teachers completed the module activities and selected different games aimed at teaching English to children in preschool and elementary education. In the last two, they illustrated, discussed, and evaluated the digital games in class following a rubric and reflected on their perception in blog posts. In this four-week research based on a mixed method and convenience sampling, quantitative and qualitative data were gathered through a pre- and post-test survey about student perceptions toward the use of video game in the classroom, class discussion, and blog posts. Statistical data analysis unveiled gender-based differences related to gameplay frequency and genre preferences. The Wilcoxon signed-rank test was used as a nonparametric statistical hypothesis test to compare the two sets of scores resulting from the same participants, and it showed a significant difference (p ≤ 0.05) after the treatment in two of the five dimensions in the survey about teacher candidates' attitudes toward game usage in education, namely, usefulness (U) and preference for video games (PVG). Research findings revealed preservice teachers' positive attitudes but lack of practical knowledge about the use of digital games in foreign-language learning. [ABSTRACT FROM AUTHOR]

Intervertebral disc (IVD) degeneration is a common cause of low back pain and most spinal disorders. As IVD degeneration is a major obstacle to the healthy life of so many individuals, it is a major issue that needs to be overcome. Currently, there is no clinical treatment for the regeneration of degenerated IVDs. However, recent advances in regenerative medicine and tissue engineering suggest the potential of cell-based and/or biomaterial-based IVD regeneration therapies. These treatments may be indicated for patients with IVDs in the intermediate degenerative stage, a point where the number of viable cells decreases, and the structural integrity of the disc begins to collapse. However, there are many biological, biomechanical, and clinical challenges that must be overcome before the clinical application of these IVD regeneration therapies can be realized. This review summarizes the basic research and clinical trials literature on cell-based and biomaterial-based IVD regenerative therapies and outlines the important role of these strategies in regenerative treatment for IVD degenerative diseases, especially disc herniation. [ABSTRACT FROM AUTHOR]

SALL4, a member of the SALL family, is an embryonic stem cell regulator involved in self-renewal and pluripotency. Recently, SALL4 overexpression was found in malignant cancers, including lung cancer, hepatocellular carcinoma, breast cancer, gastric cancer, colorectal cancer, osteosarcoma, acute myeloid leukemia, ovarian cancer, and glioma. This review updates recent advances of our knowledge of the biology of SALL4 with a focus on its mechanisms and regulatory functions in tumors and human hematopoiesis. SALL4 overexpression promotes proliferation, development, invasion, and migration in cancers through activation of the Wnt/β-catenin, PI3K/AKT, and Notch signaling pathways; expression of mitochondrial oxidative phosphorylation genes; and inhibition of the expression of the Bcl-2 family, caspase-related proteins, and death receptors. Additionally, SALL4 regulates tumor progression correlated with the immune microenvironment involved in the TNF family and gene expression through epigenetic mechanisms, consequently affecting hematopoiesis. Therefore, SALL4 plays a critical oncogenic role in gene transcription and tumor growth. However, there are still some scientific hypotheses to be tested regarding whether SALL4 is a therapeutic target, such as different tumor microenvironments and drug resistance. Thus, an in-depth understanding and study of the functions and mechanisms of SALL4 in cancer may help develop novel strategies for cancer therapy. [ABSTRACT FROM AUTHOR]