Synergistic interactions of nanoparticles and plant growth promoting rhizobacteria enhancing soil-plant systems: a multigenerational perspective.

Sustainable food security and safety are major concerns on a global scale, especially in developed nations. Adverse agroclimatic conditions affect the largest agricultural-producing areas, which reduces the production of crops. Achieving sustainable food safety is challenging because of several factors, such as soil flooding/waterlogging, ultraviolet (UV) rays, acidic/sodic soil, hazardous ions, low and high temperatures, and nutritional imbalances. Plant growth-promoting rhizobacteria (PGPR) are widely employed in in-vitro conditions because they are widely recognized as a more environmentally and sustainably friendly approach to increasing crop yield in contaminated and fertile soil. Conversely, the use of nanoparticles (NPs) as an amendment in the soil has recently been proposed as an economical way to enhance the texture of the soil and improving agricultural yields. Nowadays, various research experiments have combined or individually applied with the PGPR and NPs for balancing soil elements and crop yield in response to control and adverse situations, with the expectation that both additives might perform well together. According to several research findings, interactive applications significantly increase sustainable crop yields more than PGPR or NPs alone. The present review summarized the functional and mechanistic basis of the interactive role of PGPR and NPs. However, this article focused on the potential of the research direction to realize the possible interaction of PGPR and NPs at a large scale in the upcoming years.

Comprehensive analysis of metal(loid)s and associated metal(loid) resistance genes in atmospheric particulate matter.

Despite global concerns about metal(loid)s in atmospheric particulate matter (PM), the presence of metal(loid) resistance genes (MRGs) in PM remains unknown. Therefore, we conducted a comprehensive investigation of the metal(loid)s and associated MRGs in PMs in two seasons (summer and winter) in Xiamen, China. According to the geoaccumulation index (Igeo), most metal(loid)s, except for V and Mn, exhibited enrichment in PM, suggesting potential anthropogenic sources. By employing Positive Matrix Factorization (PMF) model, utilizing a dataset encompassing both total and bioaccessible metal(loid)s, along with backward trajectory simulations, traffic emissions were determined to be the primary potential contributor of metal(loid)s in summer, whereas coal combustion was observed to have a dominant contribution in winter. The major contributor to the carcinogenic risk of metal(loid)s in both summer and winter was predominantly attributed to coal combustion, which serves as the main source of bioaccessible Cr. Bacterial communities within PMs showed lower diversity and network complexity in summer than in winter, with Pseudomonadales being the dominant order. Abundant MRGs, including the As(III) S-adenosylmethionine methyltransferase gene (arsM), Cu(I)-translocating P-type ATPase gene (copA), Zn(II)/Cd(II)/Pb(II)-translocating P-type ATPase gene (zntA), and Zn(II)-translocating P-type ATPase gene (ziaA), were detected within the PMs. Seasonal variations were observed for the metal(loid) concentration, bacterial community structure, and MRG abundance. The bacterial community composition and MRG abundance within PMs were primarily influenced by temperature, rather than metal(loid)s. This research offers novel perspectives on the occurrence of metal(loid)s and MRGs in PMs, thereby contributing to the control of air pollution.

Bioinspired Flexible Hydrogelation with Programmable Properties for Tactile Sensing.

Tactile sensing requires integrated detection platforms with distributed and highly sensitive haptic sensing capabilities along with biocompatibility, aiming to replicate the physiological functions of the human skin and empower industrial robotic and prosthetic wearers to detect tactile information. In this regard, short peptide-based self-assembled hydrogels show promising potential to act as bioinspired supramolecular substrates for developing tactile sensors showing biocompatibility and biodegradability. However, the intrinsic difficulty to modulate the mechanical properties severely restricts their extensive employment. Herein, by controlling the self-assembly of 9-fluorenylmethoxycarbonyl-modifid diphenylalanine (Fmoc-FF) through introduction of polyethylene glycol diacrylate (PEGDA), wider nanoribbons are achieved by untwisting from well-established thinner nanofibers, and the mechanical properties of the supramolecular hydrogels can be enhanced 10-fold, supplying bioinspired supramolecular encapsulating substrate for tactile sensing. Furthermore, by doping with poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) and 9-fluorenylmethoxycarbonyl-modifid 3,4-dihydroxy-l-phenylalanine (Fmoc-DOPA), the Fmoc-FF self-assembled hydrogels can be engineered to be conductive and adhesive, providing bioinspired sensing units and adhesive layer for tactile sensing applications. Therefore, the integration of these modules results in peptide hydrogelation-based tactile sensors, showing high sensitivity and sustainable responses with intrinsic biocompatibility and biodegradability. The findings establish the feasibility of developing programmable peptide self-assembly with adjustable features for tactile sensing applications.

Nanoscale detection of carbon dots-induced changes in actin skeleton of neural cells.

Understanding the cytotoxicity of fluorescent carbon dots (CDs) is crucial for their applications, and various biochemical assays have been used to study the effects of CDs on cells. Knowledge on the effects of CDs from a biophysical perspective is integral to the recognition of their cytotoxicity, however the related information is very limited. Here, we report that atomic force microscopy (AFM) can be used as an effective tool for studying the effects of CDs on cells from the biophysical perspective. We achieve this by integrating AFM-based nanomechanics with AFM-based imaging. We demonstrate the performance of this method by measuring the influence of CDs on living human neuroblastoma (SH-SY5Y) cells at the single-cell level. We find that high-dose CDs can mechanically induce elevated normalized hysteresis (energy dissipation during the cell deformation) and structurally impair actin skeleton. The nanomechanical change highly correlates with the alteration of actin filaments, indicating that CDs-induced changes in SH-SY5Y cells are revealed in-depth from the AFM-based biophysical aspect. We validate the reliability of the biophysical observations using conventional biological methods including cell viability test, fluorescent microscopy, and western blot assay. Our work contributes new and significant information on the cytotoxicity of CDs from the biophysical perspective.

Comparative Analysis of Sucrose-Regulatory Genes in High- and Low-Sucrose Sister Clones of Sugarcane.

Sugarcane is a significant primitive source of sugar and energy worldwide. The progress in enhancing the sugar content in sugarcane cultivars remains limited due to an insufficient understanding of specific genes related to sucrose production. The present investigation examined the enzyme activities, levels of reducing and non-reducing sugars, and transcript expression using RT-qPCR to assess the gene expression associated with sucrose metabolism in a high-sucrose sugarcane clone (GXB9) in comparison to a low-sucrose sister clone (B9). Sucrose phosphate synthase (SPS), sucrose phosphate phosphatase (SPP), sucrose synthase (SuSy), cell wall invertase (CWI), soluble acid invertase (SAI), and neutral invertase (NI) are essential enzymes involved in sucrose metabolism in sugarcane. The activities of these enzymes were comparatively quantified and analyzed in immature and maturing internodes of the high- and low-sucrose clones. The results showed that the higher-sucrose-accumulating clone had greater sucrose concentrations than the low-sucrose-accumulating clone; however, maturing internodes had higher sucrose levels than immature internodes in both clones. Hexose concentrations were higher in immature internodes than in maturing internodes for both clones. The SPS and SPP enzymes activities were higher in the high-sucrose-storing clone than in the low-sucrose clone. SuSy activity was higher in the low-sucrose clone than in the high-sucrose clone; further, the degree of SuSy activity was higher in immature internodes than in maturing internodes for both clones. The SPS gene expression was considerably higher in mature internodes of the high-sucrose clones than the low-sucrose clone. Conversely, the SuSy gene exhibited up-regulated expression in the low-sucrose clone. The enhanced expression of SPS in the high-sucrose clone compared to the low-sucrose clone suggests that SPS plays a major role in the increased accumulation of sucrose. These findings provide the opportunity to improve sugarcane cultivars by regulating the activity of genes related to sucrose metabolism using transgenic techniques.

Screening of Sugarcane Proteins Associated with Defense against Leifsonia xyli subsp. xyli, Agent of Ratoon Stunting Disease.

Sugarcane is the most important sugar crop and one of the leading energy-producing crops in the world. Ratoon stunting disease (RSD), caused by the bacterium Leifsonia xyli subsp. xyli, poses a huge threat to ratoon crops, causing a significant yield loss in sugarcane. Breeding resistant varieties is considered the most effective and fundamental approach to control RSD in sugarcane. The exploration of resistance genes forms the foundation for breeding resistant varieties through molecular technology. The pglA gene is a pathogenicity gene in L. xyli subsp. xyli, encoding an endopolygalacturonase. In this study, the pglA gene from L. xyli subsp. xyli and related microorganisms was analyzed. Then, a non-toxic, non-autoactivating pglA bait was successfully expressed in yeast cells. Simultaneously the yeast two-hybrid library was generated using RNA from the L. xyli subsp. xyli-infected sugarcane. Screening the library with the pglA bait uncovered proteins that interacted with pglA, primarily associated with ABA pathways and the plant immune system, suggesting that sugarcane employs these pathways to respond to L. xyli subsp. xyli, triggering pathogenicity or resistance. The expression of genes encoding these proteins was also investigated in L. xyli subsp. xyli-infected sugarcane, suggesting multiple layers of regulatory mechanisms in the interaction between sugarcane and L. xyli subsp. xyli. This work promotes the understanding of plant-pathogen interaction and provides target proteins/genes for molecular breeding to improve sugarcane resistance to L. xyli subsp. xyli.

Recent Advances in Nanotechnology-Based Strategies for Bone Tuberculosis Management.

Bone tuberculosis, an extrapulmonary manifestation of tuberculosis, presents unique treatment challenges, including its insidious onset and complex pathology. While advancements in anti-tubercular therapy have been made, the efficacy is often limited by difficulties in achieving targeted drug concentrations and avoiding systemic toxicity. The intricate bone structure and presence of granulomas further impede effective drug delivery. Nano-drug delivery systems have emerged as a promising alternative, offering the enhanced targeting of anti-tubercular drugs. These systems, characterized by their minute size and adaptable surface properties, can be tailored to improve drug solubility, stability, and bioavailability, while also responding to specific stimuli within the bone TB microenvironment for controlled drug release. Nano-drug delivery systems can encapsulate drugs for precise delivery to the infection site. A significant innovation is their integration with prosthetics or biomaterials, which aids in both drug delivery and bone reconstruction, addressing the infection and its osteological consequences. This review provides a comprehensive overview of the pathophysiology of bone tuberculosis and its current treatments, emphasizing their limitations. It then delves into the advancements in nano-drug delivery systems, discussing their design, functionality, and role in bone TB therapy. The review assesses their potential in preclinical research, particularly in targeted drug delivery, treatment efficacy, and a reduction of side effects. Finally, it highlights the transformative promise of nanotechnology in bone TB treatments and suggests future research directions in this evolving field.

Efficient biological carbon export to the mesopelagic ocean induced by submesoscale fronts.

Oceanic submesoscale processes are ubiquitous in the North Pacific Subtropical Gyre (NPSG), where the biological carbon pump is generally ineffective. Due to difficulties in collecting continuous observations, however, it remains uncertain whether episodic submesoscale processes can drive significant changes in particulate organic carbon (POC) export into the mesopelagic ocean. Here we present observations from high-frequency Biogeochemical-Argo floats in the NPSG, which captured the enhanced POC export fluxes during the intensifying stages of a submesoscale front and a cyclonic eddy compared to their other life stages. A higher percentage of POC export flux was found to be transferred to the base of mesopelagic layer at the front compared to that at the intensifying eddy and the mean of previous studies (37% vs. ~10%), suggesting that the POC export efficiency was significantly strengthened by submesoscale dynamics. Such findings highlight the importance of submesoscale fronts for carbon export and sequestration in subtropical gyres.

The Comparison of Posterior Intervertebral Release Combined with Posterior Column Osteotomy and Posterior Column Osteotomy Alone for the Treatment of Moderate-to-Severe Rigid Scoliosis: A Prospective Controlled Study.

OBJECTIVES: There is no consensus on the treatment of moderate-to-severe rigid scoliosis. Anterior release and three-column osteotomy are excessively traumatic, whereas posterior column osteotomy (PCO) alone results in poor outcomes. An emerging surgical technique, posterior intervertebral release (PR), can release the rigid spine from the posterior approach. This study was performed to compare the multi-segment apical convex PR combined with PCO and PCO alone in patients with moderate-to-severe rigid scoliosis. METHODS: From June 2021 to June 2022, this prospective study of moderate-to-severe (Cobb: 70-90°) rigid scoliosis (flexibility of main curve <25%) involved two groups defined by surgical procedure: the PR group, the patients undergoing PR combined with PCO; and the PCO group, the patients undergoing PCO alone. Follow-up was at least 12 months. Radiographic results mainly included main curve Cobb, correction of per PR/PCO segment, apical vertebra rotation (AVR) and apical vertebra translation (AVT). Demographics, surgical data, complications were also recorded. Student's independent samples t test and Pearson's chi-square test were used to compare the differences between groups. RESULTS: Forty patients with an average age of 16.65 years were included (PR group, n = 20; PCO group, n = 20). The main curves averaged 77.56° ± 5.86° versus 78.02° ± 5.72° preoperatively and 20.07° ± 6.73° versus 33.58° ± 5.76° (p < 0.001) at the last follow-up in the PR and PCO groups, respectively. The mean correction rates were 74.30% and 56.84%, respectively (p < 0.001). The average coronal curve correction was 13.49° per release segment, which was significantly higher than the PCO correction of 6.20° (p < 0.001). The correction of apical vertebra rotation and translation in the main thoracic curve was significantly better in the PR group than in the PCO group (p < 0.05). Several minor complications in the two groups improved after conservative treatment. CONCLUSION: The multi-segment apical convex PR combined with PCO offers more advantages than PCO alone in the treatment of patients with moderate-to-severe rigid scoliosis. Owing to its excellent corrective effect and few complications, this is a high benefit-risk ratio surgical strategy for rigid scoliosis.

Nano-microplastic and agro-ecosystems: a mini-review.

Plastics' unavoidable and rampant usage causes their trash to be extensively dispersed in the atmosphere and land due to its numerous characteristics. Because of extensive plastic usage and increased manufacturing, there is insufficient recycling and a large accumulation of microplastics (MPs) in the environment. In addition to their wide availability in the soil and atmosphere, micro- and nanoplastics are becoming contaminants worldwide. Agro-ecosystem functioning and plant development are being negatively impacted in several ways by the contamination of the environment and farmland soils with MPs (<5 mm) and nanoplastics (<1 µm). The contributions of some recyclable organic waste and plastic film mulching and plastic particle deposition in agroecosystems may be substantial; therefore, it is crucial to understand any potentially hazardous or undesirable impacts of these pollutants on agroecosystems. The dissolution of bioplastics into micro- and nano-particles (MBPs and NBPs) has not been considered in recent studies, which focus primarily on agro-ecosystems. It is essential to properly understand the distribution, concentration, fate, and main source of MPs, NPS, MBPs, and NBPs in agroecosystems. Based on the limited findings, understanding the knowledge gap of environmental impact from micro and nanoplastic in farming systems does not equate to the absence of such evidence. It reveals the considerations for addressing the gaps to effectively protect global food safety and security in the near future.

Comparative evaluation of multi-fold rib and structural iliac bone grafts in single-segment thoracic and thoracolumbar spinal tuberculosis: clinical and radiological outcomes.

OBJECTIVE: To compare clinical and radiological outcomes of multi-fold rib and structural iliac bone grafts, the primary autologous graft techniques in anterolateral-only surgery for single-segment thoracic and thoracolumbar spinal tuberculosis. METHODS: This retrospective study included 99 patients treated from January 2014 to March 2022, categorized into 64 with multi-fold rib grafts (group A) and 35 with structural iliac bone grafts (group B). Outcomes assessed included hospital stay, operation time, intraoperative blood loss, postoperative drainage, complications, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the Visual Analog Scale (VAS) for pain, the Oswestry Disability Index (ODI), bone fusion time, and the American Spinal Injury Association (ASIA) impairment scale grade. Segmental kyphotic angle and intervertebral height were measured radiologically before surgery and follow-up. RESULTS: The mean follow-up was 63.50 ± 26.05 months for group A and 64.97 ± 26.43 months for group B (P > 0.05). All patients had achieved a clinical cure. Group A had a shorter operation time (P = 0.004). Within one week post-surgery, group B reported higher VAS scores (P < 0.0001). Neurological performance and quality of life significantly improved in both groups. No significant differences were observed in segmental kyphotic angle and intervertebral height between the groups pre- and postoperatively (P > 0.05). However, group A showed a greater segmental kyphotic angle at the final follow-up, while group B had better maintenance of kyphotic angle correction and intervertebral height (P < 0.05). Bone fusion was achieved in all patients without differences in fusion time (P > 0.05). CONCLUSIONS: Multi-fold rib grafts resulted in shorter operation times and less postoperative pain, while structural iliac bone grafts provided better long-term maintenance of spinal alignment and stability, suggesting their use in cases where long-term outcomes are critical.

Postoperative Sclerotic Modic Changes after Transforaminal Lumbar Interbody Fusion: The Prevalence, Risk Factors, and Impact on Fusion.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: This study aimed to assess postoperative sclerotic Modic changes (MCs) following transforaminal lumbar interbody fusion (TLIF) for lumbar degenerative disc disease (LDD), investigating their prevalence, risk factors and association with clinical outcomes. SUMMARY OF BACKGROUND DATA: Sclerotic MCs may occur in patients with LDD after lumbar interbody fusion. The incidence and characteristics of postoperative sclerotic MCs, as well as their clinical impact, are unknown. METHODS: The study included 467 patients (510 levels) who underwent single or two-level TLIF surgery, divided into a postoperative sclerotic MC group (60 patients, 66 levels) and non-MC group (407 patients, 444 levels). The time of development and location of postoperative sclerotic MCs, fusion rate, cage subsidence, bilateral process decompression, and cross-link usage were recorded. Preoperative, postoperative, and follow-up VAS and ODI scores were collected. Multivaraible logistic regression was used to evaluate factors associated with the development of postoperative sclerotic MCs. RESULTS: The prevalence of postoperative sclerotic MCs was 12.8%. The postoperative sclerotic MC group had higher BMI. The postoperative sclerotic MC group demonstrated a fusion rate of 47%, significantly lower than that of the non-MC group (71%) at 6 months post-operation. At final follow-up, the fusion rate in the postoperative sclerotic MC group was 62%, significantly lower than that of the non-MC group (86%). Post-operative VAS and ODI scores were significantly higher in the group with postoperative sclerotic MCs. BMI and osteoporosis were significantly associated with the development of postoperative sclerotic MCs. CONCLUSION: Postoperative sclerotic MCs generally appear within the first year after surgery, with a prevalence of 12.8%. The presence of postoperative sclerotic MCs can adversely impact post-operative outcomes. To prevent postoperative sclerotic MCs, we postulate extending the immobilization period with external bracing and improving the management of BMI and osteoporosis in the peri-operative time window.

Mathematical modeling of climate and fluoride effects on sugarcane photosynthesis with silicon nanoparticles.

Fluoride (F-) stress is one of the major environmental pollutant, affecting plant growth, development and production, globally. Acquisition of eco-friendly F- stress reliever seems to be the major concern these days. Consequently, application of engineered nanomaterials (ENMs) has been increasing to improve agri-economy. However, the impact of silicon nanoparticles (Si NPs) on mitigation of F- stress has not been investigated yet. Thus, the present study was conducted to compare their protective roles against F- stress by improving diurnal photosynthetic efficiency of sugarcane plant leaves. An ability of sugarcane (Saccharum officinarum cv. GT44) plants to ameliorate F- toxicity assessed through soil culture medium. After an adaptive growth phase, 45 days old plants select to examine F- mitigative efficacy of silicon nanoparticles (SiNPs: 0, 100, 300 and 500 ppm) on sugarcane plants, irrigated by F- contaminated water (0, 100, 200 and 500 ppm). Our results strongly favour that SiNPs enhanced diurnally leaf photosynthetic gas exchange viz., photosynthesis (∼1.0-29%), stomatal conductance (∼3.0-90%), and transpiration rate (∼0.5-43%), significantly, as revealed by increments in photochemical chlorophyll fluorescence efficiency of PS II linked with performance index and photosynthetic pigments during F- stress. To the best of our knowledge, this is the first investigation to explore the impact of SiNPs improving and/or maintaining the diurnal photosynthetic responses in sugarcane plants in response to F- stress. It may also precisely unlayer action of molecular mechanism(s) mediated by SiNPs, found essential for mitigation of F--toxicity to explore nano-phytoremediation approach for crop improvement and agri-economy as well.

Genome analysis of a halophilic Virgibacillus halodenitrificans ASH15 revealed salt adaptation, plant growth promotion, and isoprenoid biosynthetic machinery.

Globally, due to widespread dispersion, intraspecific diversity, and crucial ecological components of halophilic ecosystems, halophilic bacteria is considered one of the key models for ecological, adaptative, and biotechnological applications research in saline environments. With this aim, the present study was to enlighten the plant growth-promoting features and investigate the systematic genome of a halophilic bacteria, Virgibacillus halodenitrificans ASH15, through single-molecule real-time (SMRT) sequencing technology. Results showed that strain ASH15 could survive in high salinity up to 25% (w/v) NaCl concentration and express plant growth-promoting traits such as nitrogen fixation, plant growth hormones, and hydrolytic enzymes, which sustain salt stress. The results of pot experiment revealed that strain ASH15 significantly enhanced sugarcane plant growth (root shoot length and weight) under salt stress conditions. Moreover, the sequencing analysis of the strain ASH15 genome exhibited that this strain contained a circular chromosome of 3,832,903 bp with an average G+C content of 37.54%: 3721 predicted protein-coding sequences (CDSs), 24 rRNA genes, and 62 tRNA genes. Genome analysis revealed that the genes related to the synthesis and transport of compatible solutes (glycine, betaine, ectoine, hydroxyectoine, and glutamate) confirm salt stress as well as heavy metal resistance. Furthermore, functional annotation showed that the strain ASH15 encodes genes for root colonization, biofilm formation, phytohormone IAA production, nitrogen fixation, phosphate metabolism, and siderophore production, which are beneficial for plant growth promotion. Strain ASH15 also has a gene resistance to antibiotics and pathogens. In addition, analysis also revealed that the genome strain ASH15 has insertion sequences and CRISPRs, which suggest its ability to acquire new genes through horizontal gene transfer and acquire immunity to the attack of viruses. This work provides knowledge of the mechanism through which V. halodenitrificans ASH15 tolerates salt stress. Deep genome analysis, identified MVA pathway involved in biosynthesis of isoprenoids, more precisely "Squalene." Squalene has various applications, such as an antioxidant, anti-cancer agent, anti-aging agent, hemopreventive agent, anti-bacterial agent, adjuvant for vaccines and drug carriers, and detoxifier. Our findings indicated that strain ASH15 has enormous potential in industries such as in agriculture, pharmaceuticals, cosmetics, and food.

Corrigendum: Effect of endophytic diazotroph Enterobacter roggenkampii ED5 on nitrogen-metabolism-related microecology in the sugarcane rhizosphere at different nitrogen levels.

[This corrects the article DOI: 10.3389/fmicb.2023.1132016.].

Terahertz label-free detection of nicotine-induced neural cell changes and the underlying mechanisms.

Nicotine exposure can lead to neurological impairments and brain tumors, and a label-free and nondestructive detection technique is urgently required by the scientific community to assess the effects of nicotine on neural cells. Herein, a terahertz (THz) time-domain attenuated total reflection (TD-ATR) spectroscopy approach is reported, by which the effects of nicotine on normal and cancerous neural cells, i.e., HEB and U87 cells, are successfully investigated in a label/stain-free and nondestructive manner. The obtained THz absorption coefficients of HEB cells exposed to low-dose nicotine and high-dose nicotine are smaller and larger, respectively, than the untreated cells. In contrast, the THz absorption coefficients of U87 cells treated by nicotine are always smaller than the untreated cells. The THz absorption coefficients can be well related to the proliferation properties (cell number and compositional changes) and morphological changes of neural cells, by which different types of neural cells are differentiated and the viabilities of neural cells treated by nicotine are reliably assessed. Collectively, this work sheds new insights on the effects of nicotine on neural cells, and provides a useful tool (THz TD-ATR spectroscopy) for the study of chemical-cell interactions.

Comparison between Three-Dimensional Printed Titanium and PEEK Cages for Cervical and Lumbar Interbody Fusion: A Prospective Controlled Trial.

OBJECTIVES: The three-dimensional printing titanium (3DPT) cage with excellent biomechanical properties and osseointegration capabilities has been initially used in spinal fusion, while the polyetheretherketone (PEEK) cage, a bioinert material device, has been a widely used for decades with relatively excellent clinical outcomes. This study was performed to investigate the early radiographic and clinical outcomes of 3DPT cage versus PEEK cage in patients undergoing anterior cervical discectomy and fusion (ACDF) and transforaminal lumbar interbody fusion (TLIF). METHODS: This prospective controlled trial, from December 2019 to June 2022, included patients undergoing ACDF and TLIF with 3DPT cages and compared them to patients using PEEK cages for treating spinal degenerative disorders. The outcome measures included radiographic parameters (intervertebral height [IH], subsidence, fusion status, and bone-cage interface contact) and clinical outcomes (Japanese Orthopaedic Association [JOA], Neck Disability Index [NDI], Oswestry Disability Index [ODI], Short Form 12-Item Survey [SF-12], Visual Analog Scale [VAS], and Odom's criteria). Student's independent samples t test and Pearson's chi-square test were used to compare the outcome measures between the two groups before surgery and at 1 week, 3 and 6 months after surgery. RESULTS: For the patients undergoing ACDF, the 3DPT (18 patients/[26 segments]) and PEEK groups (18 patients/[26 segments]) had similar fusion rates at 3 months and 6 months follow-up (3 months: 96.2% vs. 83.3%, p = 0.182; 6 months: 100% vs. 91.7%, p = 0.225). The subsidence in the 3DPT group was significantly lower than that in the PEEK group (3 months: 0.4 ± 0.2 mm vs. 0.9 ± 0.7 mm p = 0.004; 6 months: 0.7 ± 0.3 mm vs. 1.5 ± 0.8 mm, p < 0.001). 3DPT and PEEK cage all achieved sufficient contact with the cervical endplates. For the patients undergoing TLIF, the 3DPT (20 patients/[26 segments]) and PEEK groups (20 patients/[24 segments]) had no statistical difference in fusion rate (3 months: 84.6% vs. 58.3%, p = 0.059; 6 months: 92.3% vs. 75%, p = 0.132). The subsidence was lower than that in the PEEK group without significantly difference (3 months: 0.9 ± 0.7 mm vs.1.2 ± 0.9 mm p = 0.136; 6 months: 1.6 ± 1.0 mm vs. 2.0 ± 1.0 mm, p = 0.200). At the 3-month follow-up, the bone-cage interface contact of the 3DPT cage was significantly better than that of the PEEK cage (poor contact: 15.4% vs. 75%, p < 0.001). The values of UAR were higher in the 3DPT group than in the PEEK group during the follow-up in cervical and lumbar fusion, there were more statistical differences in lumbar fusion. There were no significant differences in the clinical assessment between 3DPT or PEEK cage in spinal fusion. CONCLUSION: The 3DPT cage and PEEK cage can achieve excellent clinical outcomes in cervical and lumbar fusion. The 3DPT cage has advantage in fusion quality, subsidence severity, and bone-cage interface contact than PEEK cage.

The Effect of Halo-Pelvic Traction on Bone Mineral Density of Vertebrae and Corresponding Risk Factors.

OBJECTIVES: Decreased bone mineral density (BMD) is associated with complications in implantation surgery for severe spinal deformity. In this quantitative study, we aimed to investigate the impact of halo-pelvic traction on vertebral bone mineral density (BMD) and identify the risk factors for a decrease in BMD. METHODS: Patients who underwent halo-pelvic traction at our hospital between 2019 and 2022 were included in the study. Patients' data, including height, weight, and BMD pre- and post-traction, were collected and analyzed. Quantitative computed tomography (QCT) was used to determine the BMD. The paired rank sum test was used to evaluate the changes in each measurement parameter. Linear regression was used to identify risk factors for a decrease in BMD. RESULTS: Fifteen patients were included in the study, nine women and six men, with an average age of 21.2 ± 7.3 years. Eleven patients had severe rigid scoliosis, while four had tuberculotic kyphosis. One expert measured the BMD values of 345 vertebrae using QCT. The average traction time was 143.3 ± 44.4 days. The average pre-traction BMD was 183.1 ± 73.8 mg/cm3 , and the average post-traction BMD was 140.5 ± 61.3 mg/cm3 (p < 0.01) Patients' height increased from an average of 151.3 ± 12.8 cm pre-traction to 165.5 ± 13.7 cm post-traction (p < 0.01), with traction length averaging 14.3 ± 6.2 cm (p < 0.01). The Cobb angle of the main curve declined from an average of 112.5° ± 24.4° pre-traction to 67.7° ± 19.8° post-traction (p < 0.01). Linear regression revealed a positive correlation between BMD loss and traction length and a negative correlation between BMD loss and correction rate. CONCLUSIONS: Halo-pelvic traction can lead to a decrease in the BMD of the spinal vertebrae, with traction length positively correlated with BMD loss and correction rate negatively correlated with BMD loss. To prevent osteoporosis, physicians should ensure a limited traction length while utilizing better management techniques.

Safety, tolerability, and pharmacokinetics of an anti-LAG-3 antibody SHR-1802 in patients with advanced solid tumors: a phase I dose-escalation and dose-expansion study.

Background: Lymphocyte-activation gene 3 (LAG-3), a checkpoint molecule contributing to immune suppressive microenvironment, is regarded as a promising target in cancer treatment. SHR-1802 is a novel anti-LAG-3 monoclonal antibody. Objectives: To evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of SHR-1802. Design: A phase I dose-escalation and expansion trial of SHR-1802 in patients with advanced solid tumors. Methods: Patients with confirmed advanced solid tumors who failed previous standard-of-care or for whom no effective therapy was available were enrolled to receive SHR-1802 once every 21-day cycle. Dose escalation was performed in an accelerated titration design followed by a 3 + 3 scheme at escalating doses from 0.3 to 10 mg/kg. On the basis of results from dose-escalation phase, one or two dose levels were expanded to establish the recommended phase II dose (RP2D). The primary end points were dose-limiting toxicity (DLT) and RP2D. Results: Between 01 July 2020, and 07 September 2021, 28 patients were enrolled. No DLTs were observed, and all doses investigated were well tolerated. Treatment-related adverse events occurred in 20 patients (71.4%), all grade 1 or 2, with the most common ones being anemia (14.3%), asthenia (14.3%), electrocardiogram QT prolonged (14.3%), followed by increased blood fibrinogen (10.7%), infusion-related reaction (10.7%), and hypoalbuminemia (10.7%). No adverse event-related discontinuation occurred. Three patients died from adverse events, but none of the deaths were deemed related to study treatment. SHR-1802 exposure enhanced with the increasing doses in a greater than dose-proportional manner over the investigated dose range. The disease control rate was 32.0% (95% CI 14.9%-53.5%). The median progression-free survival was 2.0 months (95% CI 1.2-6.1). Conclusions: SHR-1802 demonstrated a tolerable safety profile and preliminary antitumor activity in patients with advanced solid tumors. Further studies with larger sample size and in combination forms are warranted for future clinical application. Registration ClinicalTrialsgov: NCT04414150.

circFAM134B is a key factor regulating reticulophagy-mediated ferroptosis in hepatocellular carcinoma.

Ferroptosis is an important mode of regulated cell death (RCD). Its inhibition is closely related to therapeutic resistance and poor prognosis in hepatocellular carcinoma (HCC). Previous reports have demonstrated ferroptosis as a biological process highly dependent on selective autophagy, such as ferritinophagy, lipophagy, and clockophagy. Our study also revealed a role for ER-phagy-mediated ferroptosis in HCC cells treated with multi-targeted tyrosine kinase inhibitors (TKIs). In the current study, we found that the homologous circular RNA (circRNA) of the family with sequence similarity 134, member B (FAM134B), hsa_circ_0128505 (was abbreviated as circFAM134B in the present study), was identified to specifically target ER-phagy to promote lenvatinib (LV)-induced ferroptosis using reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), and western blot (WB) assays in HCC cells. RNA pull-down and mass spectrometry analyses suggested that circFAM134B and FAM134B mRNA were enriched with several common interacting proteins. Among them, poly (A) binding protein cytoplasmic 4 (PABPC4) was identified as the most enriched binding partner. It was proven to be a novel antagonist against the nonsense-mediated mRNA decay (NMD) mechanism. We then applied RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter, and NMD reporter gene assays to further explore the exact role and underlying mechanism of circFAM134B-PABPC4-FAM134B axis in HCC cells. circFAM134B was confirmed as a sponge that competitively interacted with PABPC4, thereby influencing FAM134B mRNA nonsense decay. Our results provide novel evidences and strategies for the comprehensive treatment of HCC.