Risk factors for poor neurological recovery after anterior cervical discectomy and fusion: imaging characteristics.

BACKGROUND: Poor neurological recovery in patients after anterior cervical discectomy and fusion has been frequently reported; however, no study has analyzed the preoperative imaging characteristics of patients to investigate the factors affecting surgical prognosis. The purpose of this study was to investigate the factors that affect the preoperative imaging characteristics of patients and their influence on poor neurologic recovery after anterior cervical discectomy and fusion. METHODS: We retrospectively analyzed the clinical data of 89 patients who met the criteria for anterior cervical discectomy and fusion for the treatment of single-level cervical spondylotic myelopathy and evaluated the patients' neurological recovery based on the recovery rate of the Japanese Orthopaedic Association (JOA) scores at the time of the final follow-up visit. Patients were categorized into the "good" and "poor" groups based on the JOA recovery rates of ≥ 50% and < 50%, respectively. Clinical information (age, gender, body mass index, duration of symptoms, preoperative JOA score, and JOA score at the final follow-up) and imaging characteristics (cervical kyphosis, cervical instability, ossification of the posterior longitudinal ligament (OPLL), calcification of herniated intervertebral discs, increased signal intensity (ISI) of the spinal cord on T2-weighted imaging (T2WI), and degree of degeneration of the discs adjacent to the fused levels (cranial and caudal) were collected from the patients. Univariate and binary logistic regression analyses were performed to identify risk factors for poor neurologic recovery. RESULTS: The mean age of the patients was 52.56 ± 11.18 years, and the mean follow-up was 26.89 ± 11.14 months. Twenty patients (22.5%) had poor neurological recovery. Univariate analysis showed that significant predictors of poor neurological recovery were age (p = 0.019), concomitant OPLL (p = 0.019), concomitant calcification of herniated intervertebral discs (p = 0.019), ISI of the spinal cord on T2WI (p <0.05), a high grade of degeneration of the discs of the cranial neighboring levels (p <0.05), and a high grade of discs of the caudal neighboring levels (p <0.05). Binary logistic regression analysis showed that ISI of the spinal cord on T2WI (p = 0.001 OR = 24.947) and high degree of degeneration of adjacent discs on the cranial side (p = 0.040 OR = 6.260) were independent risk factors for poor neurological prognosis. CONCLUSION: ISI of the spinal cord on T2WI and high degree of cranial adjacent disc degeneration are independent risk factors for poor neurological recovery after anterior cervical discectomy and fusion. A comprehensive analysis of the patients' preoperative imaging characteristics can help in the development of surgical protocols and the management of patients' surgical expectations.

microRNA-181a-5p promotes fibroblast differentiation of mesenchymal stem cells in rats with pelvic floor dysfunction.

The use of stem cells capable of multilineage differentiation in treating Pelvic Floor Dysfunction (PFD) holds great promise since they are susceptible to entering connective tissue of various cell types and repairing damaged tissues. This research investigated the effect of microRNA-181a-5p (miR-181a-5p) on Bone Marrow Mesenchymal Stem Cells (BMSCs) in rats with PFD. BMSCs were transfected and analyzed for their fibroblast differentiation ability. miR-181a-5p, MFN1, and fibroblast-related genes were quantitatively analyzed. Whether MFN1 is a target gene of miR-181a-5p was predicted and confirmed. The efficacy of BMSCs in vivo rats with PFD was evaluated by measuring Leak Point Pressure (LPP), Conscious Cystometry (CMG), hematoxylin and eosin staining, and Masson staining. The present results discovered that miR-181a-5p was up-regulated and MFN1 was down-regulated during the differentiation of BMSCs into fibroblasts. Fibroblast differentiation of BMSCs was promoted after miR-181a-5p was induced or MFN1 was suppressed, but it was suppressed after miR-181a-5p was silenced. miR-181a-5p improved LPP and conscious CMG outcomes in PDF rats by targeting MFN1 expression, thereby accelerating fibroblast differentiation of BMSCs. In brief, miR-181a-5p induces fibroblast differentiation of BMSCs in PDF rats by MFN1, potentially targeting PDF therapeutics.

Tumor microenvironment as niche constructed by cancer stem cells: Breaking the ecosystem to combat cancer.

BACKGROUND: Cancer stem cells (CSCs) are a distinct subpopulation of cancer cells with the capacity to constantly self-renew and differentiate, and they are the main driver in the progression of cancer resistance and relapse. The tumor microenvironment (TME) constructed by CSCs is the "soil" adapted to tumor growth, helping CSCs evade immune killing, enhance their chemical resistance, and promote cancer progression. AIM OF REVIEW: We aim to elaborate the tight connection between CSCs and immunosuppressive components of the TME. We attempt to summarize and provide a therapeutic strategy to eradicate CSCs based on the destruction of the tumor ecological niche. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review is focused on three main key concepts. First, we highlight that CSCs recruit and transform normal cells to construct the TME, which further provides ecological niche support for CSCs. Second, we describe the main characteristics of the immunosuppressive components of the TME, targeting strategies and summarize the progress of corresponding drugs in clinical trials. Third, we explore the multilevel insights of the TME to serve as an ecological niche for CSCs.

Molecular characterization, expression and immune functional analysis of cystatin 10 in turbot.

BACKGROUND: Cystatin is a protease inhibitor that also regulates genes expression linked to inflammation and plays a role in defense and regulation. METHODS AND RESULTS: Cystatin 10 (Smcys10) was cloned from Scophthalmus maximus and encodes a 145 amino acid polypeptide. The results of qRT-PCR showed that Smcys10 exhibited tissue-specific expression patterns, and its expression was significantly higher in the skin than in other tissues. The expression level of Smcys10 was significantly different in the skin, gill, head kidney, spleen and macrophages after Vibrio anguillarum infection, indicating that Smcys10 may play an important role in resistance to V. anguillarum infection. The recombinant Smcys10 protein showed binding and agglutinating activity in a Ca2+-dependent manner against bacteria. rSmcys10 treatment upregulated the expression of IL-10, TNF-α and TGF-ß in macrophages of turbot and hindered the release of lactate dehydrogenase (LDH) from macrophages after V. anguillarum infection, which confirmed that rSmcys10 reduced the damage to macrophages by V. anguillarum. The NF-κB pathway was suppressed by Smcys10, as demonstrated by dual-luciferase analysis. CONCLUSIONS: These results indicated that Smcys10 is involved in the host antibacterial immune response.

Combined analysis of the effects of hypoxia and oxidative stress on DNA methylation and the transcriptome in HTR-8/SVneo trophoblast cells.

The alterations in DNA methylation and transcriptome in trophoblast cells under conditions of low oxygen and oxidative stress have major implications for pregnancy-related disorders. However, the exact mechanism is still not fully understood. In this study, we established models of hypoxia (H group) and oxidative stress (HR group) using HTR-8/SVneo trophoblast cells and performed combined analysis of genome-wide DNA methylation changes using reduced representation bisulphite sequencing and transcriptome expression changes using RNA sequencing. Our findings revealed that the H group exhibited a higher number of differentially methylated genes and differentially expressed genes than the HR group. In the H group, only 0.90% of all differentially expressed genes displayed simultaneous changes in DNA methylation and transcriptome expression. After the threshold was expanded, this number increased to 6.29% in the HR group. Notably, both the H group and HR group exhibited concurrent alterations in DNA methylation and transcriptome expression within Axon guidance and MAPK signalling pathway. Among the top 25 differentially methylated KEGG pathways in the promoter region, 11 pathways were commonly enriched in H group and HR group, accounting for 44.00%. Among the top 25 KEGG pathways in transcriptome with significant differences between the H group and HR group, 10 pathways were consistent, accounting for 40.00%. By integrating our previous data on DNA methylation from preeclamptic placental tissues, we identified that the ANKRD37 and PFKFB3 genes may contribute to the pathogenesis of preeclampsia through DNA methylation-mediated transcriptome expression under hypoxic conditions.

The role of NCAPH in cancer treatment.

Many solid tumors frequently overexpress Non-SMC Condensin I Complex Subunit H (NCAPH), and new studies suggest that NCAPH may be a target gene for clinical cancer therapy. Numerous investigations have shown that a variety of transcription factors, including as MYBL2, FOXP3, GATA3, and OTC1, can stimulate the transcription of NCAPH. Additionally, NCAPH stimulates many oncogenic signaling pathways, such as ß-Catenin/PD-L1, PI3K/AKT/SGK3, MEK/ERK, AURKB/AKT/mTOR, PI3K/PDK1/AKT, and Chk1/Chk2. Tumor immune microenvironment modification and tumor growth, apoptosis, metastasis, stemness, and treatment resistance all depend on these signals. NCAPH has the ability to form complexes with other proteins that are involved in glycolysis, DNA damage repair, and chromatin remodeling. This review indicates that NCAPH expression in most malignant tumors is associated with poor prognosis and low recurrence-free survival.

Natural products with anti-tumorigenesis potential targeting macrophage.

BACKGROUND: Inflammation is a risk factor for tumorigenesis. Macrophage, a subset of immune cells with high plasticity, plays a multifaceted role in this process. Natural products, which are bioactive compounds derived from traditional herbs or foods, have exhibited diverse effects on macrophages and tumorigenesis making them a valuable resource of drug discovery or optimization in tumor prevention. PURPOSE: Provide a comprehensive overview of the various roles of macrophages in tumorigenesis, as well as the effects of natural products on tumorigenesis by modulating macrophage function. METHODS: A thorough literature search spanning the past two decades was carried out using PubMed, Web of Science, Elsevier, and CNKI following the PRISMA guidelines. The search terms employed included "macrophage and tumorigenesis", "natural products, macrophages and tumorigenesis", "traditional Chinese medicine and tumorigenesis", "natural products and macrophage polarization", "macrophage and tumor related microenvironment", "macrophage and tumor signal pathway", "toxicity of natural products" and combinations thereof. Furthermore, certain articles are identified through the tracking of citations from other publications or by accessing the websites of relevant journals. Studies that meet the following criteria are excluded: (1) Articles not written in English or Chinese; (2) Full texts were not available; (3) Duplicate articles and irrelevant studies. The data collected was organized and summarized based on molecular mechanisms or compound structure. RESULTS: This review elucidates the multifaceted effect of macrophages on tumorigenesis, encompassing process such as inflammation, angiogenesis, and tumor cell invasion by regulating metabolism, non-coding RNA, signal transduction and intercellular crosstalk. Natural products, including vitexin, ovatodiolide, ligustilide, and emodin, as well as herbal remedies, have demonstrated efficacy in modulating macrophage function, thereby attenuating tumorigenesis. These interventions mainly focus on mitigating the initial inflammatory response or modifying the inflammatory environment within the precancerous niche. CONCLUSIONS: These mechanistic insights of macrophages in tumorigenesis offer valuable ideas for researchers. The identified natural products facilitate the selection of promising candidates for future cancer drug development.

Genome-wide identification, characterization, molecular evolution and expression profiling analysis of scavenger receptors in black rockfish (Sebastes schlegelii).

The scavenger receptors (SRs) gene family is considered as the membrane-associated pattern recognition receptors that plays important roles in the immune responses of organisms. However, there is currently limited research on the systematic identification of the SRs gene family in teleost and their role in the innate immunity of S. schegelii. In this study, we identified and annotated 15 SRs genes in S. schegelii. Through phylogenetic analysis, analysis of conserved domains, gene structure, and motif composition, we found that SRs gene family within different classes were relatively conserved. Additionally, we used qRT-PCR to analyze the expression patterns of SRs genes in immune-related tissues from healthy and Acinetobacter johnsonii-infected S. schegelii. The results showed that SRs genes exhibited different tissue expression patterns and the expression of SRs genes significantly changed after A. johnsonii infection. These results provided a valuable basis for further understanding of the functions of SRs in the innate immune response of S. schegelii.

C-type lectin 12B/4E of black rockfish (Sebastes schlegelii) macrophages as pattern recognition receptors in the antibacterial mechanism of exploration.

As lower vertebrates, fish have both innate and adaptive immune systems, but the role of the adaptive immune system is limited, and the innate immune system plays an important role in the resistance to pathogen infection. C-type lectins (CLRs) are one of the major pattern recognition receptors (PRRs) of the innate immune system. CLRs can combine with pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) to trigger NF-κB signaling pathway and exert immune efficacy. In this study, Ssclec12b and Ssclec4e of the C-type lectins, were found to be significantly up-regulated in the transcripts of Sebastes schlegelii macrophages stimulated by bacteria. The identification, expression and function of these lectins were studied. In addition, the recombinant proteins of the above two CLRs were obtained by prokaryotic expression. We found that rSsCLEC12B and rSsCLEC4E could bind to a variety of bacteria in a Ca2+-dependent manner, and promoted the agglutination of bacteria and blood cells. rSsCLEC12B and rSsCLEC4E assisted macrophages to recognize PAMPs and activate the NF-κB signaling pathway, thereby promoting the expression of inflammatory factors (TNF-α, IL-1ß, IL-6, IL-8) and regulating the early immune inflammation of macrophages. These results suggested that SsCLEC12B and SsCLEC4E could serve as PRRs in S. schlegelii macrophages to recognize pathogens and participate in the host antimicrobial immune process, and provided a valuable reference for the study of CLRs involved in fish innate immunity.

Transforming growth factor-ß (TGF-ß): A master signal pathway in teleost sex determination.

Sex determination and differentiation in fish has always been a hot topic in genetic breeding of aquatic animals. With the advances in next-generation sequencing (NGS) in recent years, sex chromosomes and sex determining genes can be efficiently identified in teleosts. To date, master sex determination genes have been elucidated in 114 species, of which 72 species have sex determination genes belonging to TGF-ß superfamily. TGF-ß is the only signaling pathway that the largest proportion of components, which including ligands (amhy, gsdfy, gdf6), receptors (amhr, bmpr), and regulator (id2bby), have opportunity recognized as a sex determination gene. In this review, we focus on the recent studies about teleost sex-determination genes within TGF-ß superfamily and propose several hypotheses on how these genes regulate sex determination process. Differing from other reviews, our review specifically devotes significant attention to all members of the TGF-ß signal pathway, not solely the sex determination genes within the TGF-ß superfamily. However, the functions of the paralogous genes of TGF superfamily are still needed ongoing research. Further studies are required to more accurately interpret the molecular mechanism of TGF-ß superfamily sex determination genes.

NosZ I carrying microorganisms determine N2O emissions from the subtropical paddy field under elevated CO2 and strongly CO2-responsive cultivar.

Elevated CO2 (eCO2) decreases N2O emissions from subtropical paddy fields, but the underlying mechanisms remain to be investigated. Herein, the response of key microbial nitrogen cycling genes to eCO2 (ambient air +200 µmol CO2 mol-1) in four rice cultivars, including two weakly CO2-responsive (W27, H5) and two strongly CO2-responsive cultivars (Y1540, L1988), was investigated. Except for nosZ I, eCO2 did not significantly alter the abundance of the other genes. NosZ I was a crucial factor governing N2O emissions, especially under eCO2 and a strongly responsive cultivar. eCO2 affected the nosZ I gene abundance (p < 0.05), for instance, the nosZ I gene abundance of cultivar W27 increased from 1.53 × 107 to 2.86 × 107 copies g-1 dw soil (p < 0.05). In the nosZ I microbial community, the known taxa were mainly Pseudomonadota (phylum) (19.74-31.72 %) and Alphaproteobacteria (class) (0.56-13.12 %). In the nosZ I community assembly process, eCO2 enhanced the role of stochasticity, increasing from 35 % to 85 % (p < 0.05), thereby inducing diffusion limitations of weakly responsive cultivars to dominate (67 %). Taken together, the increase in nosZ I gene abundance is a potential reason for the alleviation of N2O emissions from subtropical paddy fields under eCO2.

Strigolactones shape the assembly of root-associated microbiota in response to phosphorus availability.

Plants rely on strigolactones (SLs) to regulate their development and form symbiotic relationships with microbes as part of the adaptive phosphorus (P) efficiency strategies. However, the impact of SLs on root-associated microbial communities in response to P availability remains unknown. Here, root microbiota of SL biosynthesis (max3-11) and perception (d14-1) were compared to wild-type Col-0 plants under different P concentrations. Using high-throughput sequencing, the relationship between SLs, P concentrations, and the root-associated microbiota was investigated to reveal the variation in microbial diversity, composition, and interaction. Plant genotypes and P availability played important but different roles in shaping the root-associated microbial community. Importantly, SLs were found to attract Acinetobacter in low P conditions, which included an isolated CP-2 (Acinetobacter soli) that could promote plant growth in cocultivation experiments. Moreover, SLs could change the topologic structure within co-occurrence networks and increase the number of keystone taxa (e.g., Rhizobiaceae and Acidobacteriaceae) to enhance microbial community stability. This study reveals the key role of SLs in mediating root-associated microbiota interactions.IMPORTANCEStrigolactones (SLs) play a crucial role in plant development and their symbiotic relationships with microbes, particularly in adapting to phosphorus levels. Using high-throughput sequencing, we compared the root microbiota of plants with SL biosynthesis and perception mutants to wild-type plants under different phosphorus concentrations. These results found that SLs can attract beneficial microbes in low phosphorus conditions to enhance plant growth. Additionally, SLs affect microbial network structures, increasing the stability of microbial communities. This study highlights the key role of SLs in shaping root-associated microbial interactions, especially in response to phosphorus availability.

[Analysis of imaging characteristics and effectiveness of cervical spondylotic myelopathy with cervical kyphosis].

Objective: To investigate the imaging characteristics of cervical kyphosis and spinal cord compression in cervical spondylotic myelopathy (CSM) with cervical kyphosis and the influence on effectiveness. Methods: The clinical data of 36 patients with single-segment CSM with cervical kyphosis who were admitted between January 2020 and December 2022 and met the selection criteria were retrospectively analyzed. The patients were divided into 3 groups according to the positional relationship between the kyphosis focal on cervical spine X-ray film and the spinal cord compression point on MRI: the same group (group A, 20 cases, both points were in the same position), the adjacent group (group B, 10 cases, both points were located adjacent to each other), and the separated group (group C, 6 cases, both points were located >1 vertebra away from each other). There was no significant difference between groups ( P>0.05) in baseline data such as gender, age, body mass index, lesion segment, disease duration, and preoperative C 2-7 angle, C 2-7 sagittal vertical axis (C 2-7 SVA), C 7 slope (C 7S), kyphotic Cobb angle, fusion segment height, and Japanese Orthopedic Association (JOA) score. The patients underwent single-segment anterior cervical discectomy with fusion (ACDF). The occurrence of postoperative complications was recorded; preoperatively and at last follow-up, the patients' neurological function was evaluated using the JOA score, and the sagittal parameters (C 2-7 angle, C 2-7 SVA, C 7S, kyphotic Cobb angle, and height of the fused segments) were measured on cervical spine X-ray films and MRI and the correction rate of the cervical kyphosis was calculated; the correlation between changes in cervical sagittal parameters before and after operation and the JOA score improvement rate was analyzed using Pearson correlation analysis. Results: In 36 patients, only 1 case of dysphagia occurred in group A, and the dysphagia symptoms disappeared at 3 days after operation, and the remaining patients had no surgery-related complications during the hospitalization. All patients were followed up 12-42 months, with a mean of 20.1 months; the difference in follow-up time between the groups was not significant ( P>0.05). At last follow-up, all the imaging indicators and JOA scores of patients in the 3 groups were significantly improved when compared with preoperative ones ( P<0.05). The correction rate of cervical kyphosis in group A was significantly better than that in group C, and the improvement rate of JOA score was significantly better than that in groups B and C, all showing significant differences ( P<0.05), and there was no significant difference between the other groups ( P>0.05). The correlation analysis showed that the improvement rate of JOA score was negatively correlated with C 2-7 angle and kyphotic Cobb angle at last follow-up ( r=-0.424, P=0.010; r=-0.573, P<0.001), and positively correlated with the C 7S and correction rate of cervical kyphosis at last follow-up ( r=0.336, P=0.045; r=0.587, P<0.001), and no correlation with the remaining indicators ( P>0.05). Conclusion: There are three main positional relationships between the cervical kyphosis focal and the spinal cord compression point on imaging, and they have different impacts on the effectiveness and sagittal parameters after ACDF, and those with the same position cervical kyphosis focal and spinal cord compression point have the best improvement in effectiveness and sagittal parameters.

Accuracy of the novel digital non-cross-arch surgical guides with integration of tooth undercut retention and screw-bone support for implant placement in mandibular free-end.

BACKGROUND: Large cross-arch free-end surgical guides can obscure the visual field, compromising surgical accuracy due to insufficient stability at the free-end. This in vitro study aims to evaluate the accuracy of novel digital non-cross-arch surgical guides designed for implant placement at the mandibular free-end, incorporating tooth undercut retention and screw-bone support. MATERIALS AND METHODS: A mandibular dental model lacking left molars was utilized to fabricate unilateral (cross-arch) tooth-supported surgical guides (GT I, n = 20). Subsequently, two additional types of surgical guides were fabricated: GT II (covering two teeth, n = 20) and GT III (covering three teeth, n = 20). These novel surgical guides were designed to utilize the undercut of the supporting teeth for retention and enhance stability with screw-bone support at the guide's free-end. Furthermore, 60 identical guiding blocks were assembled on the three types of surgical guides to facilitate the implants' insertion. On a phantom head, 120 implant replicas were placed at the Federal Dentaire Internationale (FDI) teeth positions #36 and #37 on the dental model, employing a combination of surgical guides and guiding blocks. To assess accuracy, planned and placed implant positions were compared using intraoral optical scanning. Discrepancies in angulation and linear deviations, including the coronal/apical 3D deviations, lateral deviation as well as depth deviation, were measured. Statistical analysis was performed using two-way ANOVA and Bonferroni test (α = 0.05). RESULTS: GT I exhibited significantly largest discrepancies, including angular and linear deviations at the crest and apex at every implant site. Especially in depth, at implant site #36, the mean deviation value of GT I (0.27 ± 0.13 mm) was twice as large as GT III (0.13 ± 0.07 mm), and almost twice as large as GT II (0.14 ± 0.08 mm). However, at implant site #37, this deviation increased to almost a five-fold relationship between GT I (0.63 ± 0.12 mm) and II (0.14 ± 0.09 mm), as well as between GT I and III (0.13 ± 0.09 mm). No significant discrepancies existed between the novel surgical guides at either implant site #36 or #37. CONCLUSION: This study provides a practical protocol for enhancing accuracy of implant placement and reducing the size of free-end surgical guides used at mandibular molar sites.

A polyetheretherketone framework removable partial denture for a 6-year-old child with nonsyndromic oligodontia made using glass-ceramic hemispheres to enhance retention: A clinical report.

A 6-year-old child with nonsyndromic oligodontia in the mixed dentition received a removable dental prosthesis with a polyetheretherketone framework and artificial gingiva, restoring esthetics and function. Computer-aided design and computer-aided manufacturing hemispherical glass-ceramic attachments were added to the teeth under the guidance of acid-etching and bonding guides to obtain an undercut area. The bonding and cementation of the attachments and the prosthesis delivery were completed in a single visit. This method offers a suitable prosthodontic treatment option for treating children with oligodontia in the mixed dentition.

Effect of Polymer and Crosslinker Concentration on Static and Dynamic Gelation Behavior of Phenolic Resin Hydrogel.

The application results of profile control and water plugging technology are highly related to the gelation time and strength of phenolic resin hydrogel. In this work, a hydrogel solution was prepared by fully mixing the prepared polymer solution with a crosslinker. The static gelation process of PFR hydrogel in ampoule bottles and porous media was analyzed by changes in the viscosity and residual resistance coefficient. Then, the dynamic gelation of the PFR hydrogel in porous media was tested using a circulating flow device, and the changes in viscosity and injection pressure were analyzed during the dynamic gelation process. Finally, the effects of the polymer concentration and crosslinker concentration on dynamic gelation were analyzed. The initial gelation time and final gelation time in porous media were 1-1.5 times and 1.5-2 times those in ampoule bottles under static conditions, respectively. The initial dynamic gelation time in porous media was 2-2.5 times and 1.5-2 times the initial static gelation times in ampoule bottles and porous media, respectively. The final dynamic gelation time was four times and two times the initial static gelation times in ampoule bottles and porous media, respectively. The production after dynamic gelation in porous media comprised hydrogel aggregates and water fluid, leading to a high injection pressure and low viscosity of the produced liquid. As the concentration of polymer and crosslinker increased, the dynamic gelation time was shortened and the gel strength was increased. In the dynamic gelation process in porous media, the phenol resin hydrogel could migrate deeply, but it was limited by the concentrations of the polymer and crosslinker. The results of subsequent water flooding showed that the polymer hydrogel had a good plugging ability after dynamic gelation. The deep reservoir could only be blocked off in the subsequent water flooding process when the migration of hydrogel happened in the dynamic gelation process.

Hydrogen Embrittlement as a Conspicuous Material Challenge─Comprehensive Review and Future Directions.

Hydrogen is considered a clean and efficient energy carrier crucial for shaping the net-zero future. Large-scale production, transportation, storage, and use of green hydrogen are expected to be undertaken in the coming decades. As the smallest element in the universe, however, hydrogen can adsorb on, diffuse into, and interact with many metallic materials, degrading their mechanical properties. This multifaceted phenomenon is generically categorized as hydrogen embrittlement (HE). HE is one of the most complex material problems that arises as an outcome of the intricate interplay across specific spatial and temporal scales between the mechanical driving force and the material resistance fingerprinted by the microstructures and subsequently weakened by the presence of hydrogen. Based on recent developments in the field as well as our collective understanding, this Review is devoted to treating HE as a whole and providing a constructive and systematic discussion on hydrogen entry, diffusion, trapping, hydrogen-microstructure interaction mechanisms, and consequences of HE in steels, nickel alloys, and aluminum alloys used for energy transport and storage. HE in emerging material systems, such as high entropy alloys and additively manufactured materials, is also discussed. Priority has been particularly given to these less understood aspects. Combining perspectives of materials chemistry, materials science, mechanics, and artificial intelligence, this Review aspires to present a comprehensive and impartial viewpoint on the existing knowledge and conclude with our forecasts of various paths forward meant to fuel the exploration of future research regarding hydrogen-induced material challenges.

Co-delivery of Plinabulin and Tirapazamine boosts anti-tumor efficacy by simultaneously destroying tumor blood vessels and killing tumor cells.

It is imperative to optimize chemotherapy for heightened anti-tumor therapeutic efficacy. Unrestrained tumor cell proliferation and sustained angiogenesis are pivotal for cancer progression. Plinabulin, a vascular disrupting agent, selectively destroys tumor blood vessels. Tirapazamine (TPZ), a hypoxia-activated prodrug, intensifies cytotoxicity in diminishing oxygen levels within tumor cells. Despite completing Phase III clinical trials, both agents exhibited modest treatment efficiency due to dose-limiting toxicity. In this study, we employed methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-b-PDLLA) to co-deliver Plinabulin and TPZ to the tumor site, concurrently disrupting blood vessels and eliminating tumor cells, addressing both symptoms and the root cause of tumor progression. Plinabulin was converted into a prodrug with esterase response (PSM), and TPZ was synthesized into a hexyl chain-containing derivative (TPZHex) for effective co-delivery. PSM and TPZHex were co-encapsulated with mPEG-b-PDLLA, forming nanodrugs (PT-NPs). At the tumor site, PT-NPs responded to esterase overexpression, releasing Plinabulin, disrupting blood vessels, and causing nutritional and oxygen deficiency. TPZHex was activated in response to increased hypoxia, killing tumor cells. In treating 4T1 tumors, PT-NPs demonstrated enhanced therapeutic efficacy, achieving a 92.9 % tumor suppression rate and a 20 % cure rate. This research presented an innovative strategy to enhance synergistic efficacy and reduce toxicity in combination chemotherapy.

Immunometabolism in cancer: basic mechanisms and new targeting strategy.

Maturing immunometabolic research empowers immune regulation novel approaches. Progressive metabolic adaptation of tumor cells permits a thriving tumor microenvironment (TME) in which immune cells always lose the initial killing capacity, which remains an unsolved dilemma even with the development of immune checkpoint therapies. In recent years, many studies on tumor immunometabolism have been reported. The development of immunometabolism may facilitate anti-tumor immunotherapy from the recurrent crosstalk between metabolism and immunity. Here, we discuss clinical studies of the core signaling pathways of immunometabolism and their inhibitors or agonists, as well as the specific functions of these pathways in regulating immunity and metabolism, and discuss some of the identified immunometabolic checkpoints. Understanding the comprehensive advances in immunometabolism helps to revise the status quo of cancer treatment. An overview of the new landscape of immunometabolism. The PI3K pathway promotes anabolism and inhibits catabolism. The LKB1 pathway inhibits anabolism and promotes catabolism. Overactivation of PI3K/AKT/mTOR pathway and IDO, IL4I1, ACAT, Sirt2, and MTHFD2 promote immunosuppression of TME formation, as evidenced by increased Treg and decreased T-cell proliferation. The LKBI-AMPK pathway promotes the differentiation of naive T cells to effector T cells and memory T cells and promotes anti-tumor immunity in DCs.

Three dimensionally printed template with an interproximal isolation design guide consecutive closure of multiple diastema with injectable resin composite.

OBJECTIVE: This article describes a novel 3D-printed template armed with interproximal matrices to isolate interproximal contact areas and guide injectable resin composite for consecutive closure of multiple diastema. CLINICAL CONSIDERATIONS: Among several treatment options proposed for diastema closure, direct resin composite is noninvasive and easy to repair. The "composite injection technique" has been introduced to improve time efficiency and reduce technique sensitivity for clinicians. However, in the case of multiple diastema, the overflow of excess resin materials onto the adjacent teeth during injection poses challenges for recontouring the interproximal anatomy. A 3D-printed template with special-designed gaps at interproximal areas was designed and fabricated based on a virtual diagnostic wax-up. Flowable resin composite was then consecutively injected through the template to close diastemata at multiple adjacent teeth. CONCLUSION: This technique using a 3D-printed template with interproximal isolation design contributed to an efficient and accurate operation for multiple anterior diastema closure. CLINICAL SIGNIFICANCE: Efficient and accurate freehand buildups of composite restoration for multiple diastema are challenging in operative dentistry. The described noninvasive full digital workflow provides a predictable method to accurately recontour the multiple target restorations and reduce the chair-side time and technical sensitivity.