Does Focal Kyphotic Deformity at Non-responsible Levels Affect the Outcomes of Anterior Cervical Decompression and Fusion?

OBJECTIVE: Focal cervical kyphotic deformity (FCK) without neurologic compression is not uncommon in patients with cervical spondylotic myelopathy (CSM) who underwent anterior cervical decompression and fusion (ACDF) surgery. It remains unclear whether FCK at non-responsible levels needs to be treated simultaneously. This study aims to investigate whether FCK at non-responsible levels is the prognostic factor for CSM and elucidate the surgical indication for FCK. METHODS: Patients with CSM who underwent ACDF between January 2016 and April 2021 were included. Patients were divided into two groups according to the presence of FCK and two classifications according to global cervical sagittal alignment. Clinical outcomes were compared using Japanese Orthopaedic Association (JOA) scores and recovery rate (RR) of neurologic function. Univariate and multivariate analysis based on RR assessed the relationship between various possible prognostic factors and clinical outcomes. The receiver operating characteristic curve (ROC) was used to determine the optimal cutoff value of the focal Cobb angle to predict poor clinical outcomes. RESULTS: A total of 94 patients were included, 41 with FCK and 53 without. Overall, the RR of neurologic function was significantly lower in the FCK than in the non-FCK group. Further analysis showed that the RR difference between the two groups was only observed in hypo-lordosis classification (kyphotic and sigmoid alignment), but not in the lordosis classification. Multivariate analysis showed that the preoperative focal Cobb angle in the FCK level (OR = 0.42; 95% CI = 0.18-0.97) was independently associated with clinical outcomes in the hypo-lordosis classification. The optimal cutoff point of the preoperative focal kyphotic Cobb angle was calculated at 4.05°. CONCLUSION: For CSM with hypo-lordosis, FCK was a risk factor for poor postoperative outcomes. Surgeons may consider treating the FCK simultaneously if the focal kyphotic Cobb angle of FCK is greater than 4.05° and is accompanied by cervical global kyphotic or sigmoid deformity.

Transcription factor OsSHR2 regulates rice architecture and yield per plant in response to nitrogen.

MAIN CONCLUSION: Mutation of OsSHR2 adversely impacted root and shoot growth and impaired plant response to N conditions, further reducing the yield per plant. Nitrogen (N) is a crucial factor that regulates the plant architecture. There is still a lack of research on it. In our study, it was observed that the knockout of the SHORTROOT 2 (OsSHR2) which was induced by N deficiency, can significantly affect the regulation of plant architecture response to N in rice. Under N deficiency, the mutation of OsSHR2 significantly reduced root growth, and impaired the sensitivity of the root meristem length to N deficiency. The mutants were found to have approximately a 15% reduction in plant height compared to wild type. But mutants showed a significant increase in tillering at post-heading stage, approximately 26% more than the wild type, particularly in high N conditions. In addition, due to reduced seed setting rate and 1000-grain weight, mutant yield was significantly decreased by approximately 33% under low N fertilizer supply. The mutation also changed the distribution of N between the vegetative and reproductive organs. Our findings suggest that the transcription factor OsSHR2 plays a regulatory role in the response of plant architecture and yield per plant to N in rice.

Studying protein stability in crowded environments by NMR.

Most proteins perform their functions in crowded and complex cellular environments where weak interactions are ubiquitous between biomolecules. These complex environments can modulate the protein folding energy landscape and hence affect protein stability. NMR is a nondestructive and effective method to quantify the kinetics and equilibrium thermodynamic stability of proteins at an atomic level within crowded environments and living cells. Here, we review NMR methods that can be used to measure protein stability, as well as findings of studies on protein stability in crowded environments mimicked by polymer and protein crowders and in living cells. The important effects of chemical interactions on protein stability are highlighted and compared to spatial excluded volume effects.

Beneficial rhizobacterium Bacillus velezensis SQR9 regulates plant nitrogen uptake via endogenous signaling pathway.

Nitrogen fertilizer is widely used in agriculture to boost crop yields, plant growth-promoting rhizobacteria (PGPRs) can increase plant nitrogen use efficiency through nitrogen fixation and organic nitrogen mineralization. However, it is not known if they can activate the plant uptake of nitrogen. In this study, we investigated the effects of a PGPR strain Bacillus velezensis SQR9-emitted volatile compounds (VCs) on plant nitrogen uptake. Strain SQR9 VCs promoted nitrogen accumulation in both rice and Arabidopsis. In addition, isotope labeling experiments showed that strain SQR9 VCs promoted the absorption of nitrate and ammonium. Several key nitrogen uptake genes were up-regulated by strain SQR9 VCs, such as AtNRT2.1 in Arabidopsis and OsNAR2.1, OsNRT2.3a and OsAMT1 family members in rice, and the deletion of these genes compromised the promoting effect of SQR9 VCs on plant nitrogen absorption. Furthermore, the calcium (Ca2+) and transcription factor NIN-LIKE PROTEIN 7 play an important role in strain SQR9 VCs-promoted nitrate uptake. Taken together, our results suggest that PGPRs can promote nitrogen uptake through regulating the plant's endogenous signaling and nitrogen transport pathways.

Interaction between Aß and tau on reversion and conversion in mild cognitive impairment patients: After 2-year follow-up.

Background: The role of amyloid-ß (Aß) and tau in reversion and conversion in patients with mild cognitive impairment (MCI) remains unclear. This study aimed to investigate the influence of cerebrospinal fluid (CSF) Aß and tau on reversion and conversion and the temporal sequence of their pathogenicity in MCI patients. Methods: 179 MCI patients were recruited from the Alzheimer's Disease Neuroimaging Initiative database and classified into two groups based on cognitive changes after follow-up: reversal group (MCI to cognitively normal) and conversion group (MCI to Alzheimer's disease). CSF biomarkers and cognitive function were measured at baseline and 2-year follow-up. Partial correlation was used to analyze the association between CSF biomarkers and cognitive function, and multivariable logistic regression to identify independent risk factors for cognitive changes at baseline and 2-year follow-up. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive ability of these risk factors for cognitive changes. Results: The differences in cognitive function and CSF biomarkers between the two groups remained consistent with baseline after 2-year follow-up. After controlling for confounding variables, there was still a correlation between CSF biomarkers and cognitive function at baseline and 2-year follow-up. Multivariable regression analysis found that at baseline, only Aß level was independently associated with cognitive changes, while Aß and tau were both predictive factors after 2-year follow-up. ROC curve analysis revealed that the combination of Aß and tau [area under the curve (AUC) 0.91, sensitivity 84%, specificity 86%] in predicting cognitive changes after 2-year follow-up had better efficacy than baseline Aß alone (AUC 0.81). Conclusion: Aß may precede Tau in causing cognitive changes, and the interaction between the two mediates cognitive changes in patients. This study provides new clinical evidence to support the view that Aß pathology precedes tau pathology, which together contribute to the changes in cognitive function.

Multifunctional biomimetic hydrogel dressing provides anti-infection treatment and improves immunotherapy by reprogramming the infection-related wound microenvironment.

The advancement of biomaterials with antimicrobial and wound healing properties continues to present challenges. Macrophages are recognized for their significant role in the repair of infection-related wounds. However, the interaction between biomaterials and macrophages remains complex and requires further investigation. In this research, we propose a new sequential immunomodulation method to enhance and expedite wound healing by leveraging the immune properties of bacteria-related wounds, utilizing a novel mixed hydrogel dressing. The hydrogel matrix is derived from porcine acellular dermal matrix (PADM) and is loaded with a new type of bioactive glass nanoparticles (MBG) doped with magnesium (Mg-MBG) and loaded with Curcumin (Cur). This hybrid hydrogel demonstrates controlled release of Cur, effectively eradicating bacterial infection in the early stage of wound infection, and the subsequent release of Mg ions (Mg2+) synergistically inhibits the activation of inflammation-related pathways (such as MAPK pathway, NF-κB pathway, TNF-α pathway, etc.), suppressing the inflammatory response caused by infection. Therefore, this innovative hydrogel can safely and effectively expedite wound healing during infection. Our design strategy explores novel immunomodulatory biomaterials, offering a fresh approach to tackle current clinical challenges associated with wound infection treatment.

19F Nuclear Magnetic Resonance Fingerprinting Technique for Identifying and Quantifying G-Quadruplex Topology in Human Telomeric Overhangs.

G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures with diverse topological features and biological roles. Human telomeric (Htelo) overhangs consisting of TTAGGG repeats can fold into G4s that adopt different topologies under physiological conditions. These G4s are potential targets for anticancer drugs. Despite intensive research, the existence and topology of G4s at Htelo overhangs in vivo are still unclear because there is no method to distinguish and quantify the topology of Htelo overhangs with native lengths that can form more than three tandem G4s in living cells. Herein, we present a novel 19F chemical shift fingerprinting technique to identify and quantify the topology of the Htelo overhangs up to five G-quadruplexes (G4s) and 120 nucleotides long both in vitro and in living cells. Our results show that longer overhang sequences tend to form stable G4s at the 5'- and 3'-ends, while the interior G4s are dynamic and "sliding" along the sequence, with TTA or 1-3 TTAGGG repeats as a linker. Each G4 in the longer overhang is conformationally heterogeneous, but the predominant ones are hybrid-2, two- or three-tetrad antiparallel, and hybrid-1 at the 5'-terminal, interior, and 3'-terminal, respectively. Additionally, we observed a distinct behavior of different lengths of telomeric sequences in living cells, suggesting that the overhang length and protein accessibility are related to its function. This technique provides a powerful tool for quickly identifying the folding topology and relative population of long Htelo overhangs, which may provide valuable insights into telomere functionality and be beneficial for structure-based anticancer drug development targeting G4s.

Genome-wide DNA methylation and transcriptomic patterns of precancerous gastric cardia lesions.

BACKGROUND: Intestinal metaplasia (IM) and intraepithelial neoplasia (IEN) are considered precursors of gastric cardia cancer (GCC). Here, we investigated the histopathologic and molecular profiles of precancerous gastric cardia lesions (PGCLs) and biomarkers for risk stratification of gastric cardia IM. METHODS: We conducted a hospital-based evaluation (n = 4578) for PGCL profiles in high-incidence and non-high-incidence regions for GCC in China. We next performed 850K methylation arrays (n = 42) and RNA-seq (n = 44) in tissues with PGCLs. We then examined the protein expression of candidate biomarker using immunohistochemistry. RESULTS: Of the 4578 participants, 791 were diagnosed with PGCLs (600 IM, 62 IM with IEN, and 129 IEN). We found that individuals from high-incidence regions (26.7%) were more likely to develop PGCLs than those from non-high-incidence areas (13.5%). DNA methylation and gene expression alterations, indicated by differentially methylated probes (DMPs) and differentially expressed genes (DEGs), exhibited a progressive increase from type I IM (DMP = 210, DEG = 24), type II IM (DMP = 3402, DEG = 129), to type III IM (DMP = 3735, DEG = 328), peaking in IEN (DMP = 47 373, DEG = 2278). Three DEGs with aberrant promoter methylation were identified, shared exclusively by type III IM and IEN. Of these DEGs, we found that OLFM4 expression appears in IMs and increases remarkably in IENs (P < .001). CONCLUSIONS: We highlight that type III IM and IEN share similar epigenetic and transcriptional features in gastric cardia and propose biomarkers with potential utility in risk prediction.

Root architecture and rhizosphere-microbe interactions.

Plant roots fulfil crucial tasks during a plant's life. As roots encounter very diverse conditions while exploring the soil for resources, their growth and development must be responsive to changes in the rhizosphere, resulting in root architectures that are tailor-made for all prevailing circumstances. Using multi-disciplinary approaches, we are gaining more intricate insights into the regulatory mechanisms directing root system architecture. This Special Issue provides insights into our advancement of knowledge on different aspects of root development and identifies opportunities for future research.

Auxin receptor OsTIR1 mediates auxin signaling during seed filling in rice.

Cereal endosperm represents the most important source of the world's food. Nevertheless, the molecular mechanisms behind sugar import into rice (Oryza sativa) endosperm and their relationship with auxin signaling are poorly understood. Here, we report that auxin transport inhibitor response 1 (TIR1) plays an essential role in rice grain yield and quality via modulating sugar transport into endosperm. The fluctuations of OsTIR1 transcripts parallel to the early stage of grain expansion among those of the 5 TIR1/AFB (auxin-signaling F-box) auxin co-receptor proteins. OsTIR1 is abundantly expressed in ovular vascular trace, nucellar projection, nucellar epidermis, aleurone layer cells, and endosperm, providing a potential path for sugar into the endosperm. Compared to wild-type (WT) plants, starch accumulation is repressed by mutation of OsTIR1 and improved by overexpression of the gene, ultimately leading to reduced grain yield and quality in tir1 mutants but improvement in overexpression lines. Of the rice AUXIN RESPONSE FACTOR (ARF) genes, only the OsARF25 transcript is repressed in tir1 mutants and enhanced by overexpression of OsTIR1; its highest transcript is recorded at 10 d after fertilization, consistent with OsTIR1 expression. Also, OsARF25 can bind the promoter of the sugar transporter OsSWEET11 (SWEET, sugars will eventually be exported transporter) in vivo and in vitro. arf25 and arf25/sweet11 mutants exhibit reduced starch content and seed size (relative to the WTs), similar to tir1 mutants. Our data reveal that OsTIR1 mediates sugar import into endosperm via the auxin signaling component OsARF25 interacting with sugar transporter OsSWEET11. The results of this study are of great significance to further clarify the regulatory mechanism of auxin signaling on grain development in rice.

The transcription factor MYB110 regulates plant height, lodging resistance, and grain yield in rice.

The high-yielding Green Revolution varieties of cereal crops are characterized by a semidwarf architecture and lodging resistance. Plant height is tightly regulated by the availability of phosphate (Pi), yet the underlying mechanism remains obscure. Here, we report that rice (Oryza sativa) R2R3-type Myeloblastosis (MYB) transcription factor MYB110 is a Pi-dependent negative regulator of plant height. MYB110 is a direct target of PHOSPHATE STARVATION RESPONSE 2 (OsPHR2) and regulates OsPHR2-mediated inhibition of rice height. Inactivation of MYB110 increased culm diameter and bending resistance, leading to enhanced lodging resistance despite increased plant height. Strikingly, the grain yield of myb110 mutants was elevated under both high- and low-Pi regimes. Two divergent haplotypes based on single nucleotide polymorphisms in the putative promoter of MYB110 corresponded with its transcript levels and plant height in response to Pi availability. Thus, fine-tuning MYB110 expression may be a potent strategy for further increasing the yield of Green Revolution cereal crop varieties.

Signal communication during microbial modulation of root system architecture.

Every living organism on Earth depends on its interactions with other organisms. In the rhizosphere, plants and microorganisms constantly exchange signals and influence each other's behavior. Recent studies have shown that many beneficial rhizosphere microbes can produce specific signaling molecules that affect plant root architecture and therefore could have substantial effects on above-ground growth. This review examines these chemical signals and summarizes their mechanisms of action, with the aim of enhancing our understanding of plant-microbe interactions and providing references for the comprehensive development and utilization of these active components in agricultural production. In addition, we highlight future research directions and challenges, such as searching for microbial signals to induce primary root development.

Copper-Zinc-Doped Bilayer Bioactive Glasses Loaded Hydrogel with Spatiotemporal Immunomodulation Supports MRSA-Infected Wound Healing.

Developing biomaterials with antimicrobial and wound-healing activities for the treatment of wound infections remains challenging. Macrophages play non-negligible roles in healing infection-related wounds. In this study, a new sequential immunomodulatory approach is proposed to promote effective and rapid wound healing using a novel hybrid hydrogel dressing based on the immune characteristics of bacteria-associated wounds. The hydrogel dressing substrate is derived from a porcine dermal extracellular matrix (PADM) and loaded with a new class of bioactive glass nanoparticles (BGns) doped with copper (Cu) and zinc (Zn) ions (Cu-Zn BGns). This hybrid hydrogel demonstrates a controlled release of Cu2+ and Zn2+ and sequentially regulates the phenotypic transition of macrophages from M1 to M2 by alternately activating nucleotide-binding oligomerization domain (NOD) and inhibiting mitogen-activated protein kinases (MAPK) signaling pathways. Additionally, its dual-temporal bidirectional immunomodulatory function facilitates enhanced antibacterial activity and wound healing. Hence, this novel hydrogel is capable of safely and efficiently accelerating wound healing during infections. As such, the design strategy provides a new direction for exploring novel immunomodulatory biomaterials to address current clinical challenges related to the treatment of wound infections.

TMEM135 maintains the equilibrium of osteogenesis and adipogenesis by regulating mitochondrial dynamics.

BACKGROUND: Disturbance in the differentiation process of bone marrow mesenchymal stem cells (BMSCs) leads to osteoporosis. Mitochondrial dynamics plays a pivotal role in the metabolism and differentiation of BMSCs. However, the mechanisms underlying mitochondrial dynamics and their impact on the differentiation equilibrium of BMSCs remain unclear. METHODS: We investigated the mitochondrial morphology and markers related to mitochondrial dynamics during BMSCs osteogenic and adipogenic differentiation. Bioinformatics was used to screen potential genes regulating BMSCs differentiation through mitochondrial dynamics. Subsequently, we evaluated the impact of Transmembrane protein 135 (TMEM135) deficiency on bone homeostasis by comparing Tmem135 knockout mice with their littermates. The mechanism of TMEM135 in mitochondrial dynamics and BMSCs differentiation was also investigated in vivo and in vitro. RESULTS: Distinct changes in mitochondrial morphology were observed between osteogenic and adipogenic differentiation of BMSCs, manifesting as fission in the late stage of osteogenesis and fusion in adipogenesis. Additionally, we revealed that TMEM135, a modulator of mitochondrial dynamics, played a functional role in regulating the equilibrium between adipogenesis and osteogenesis. The TMEM135 deficiency impaired mitochondrial fission and disrupted crucial mitochondrial energy metabolism during osteogenesis. Tmem135 knockout mice showed osteoporotic phenotype, characterized by reduced osteogenesis and increased adipogenesis. Mechanistically, TMEM135 maintained intracellular calcium ion homeostasis and facilitated the dephosphorylation of dynamic-related protein 1 at Serine 637 in BMSCs. CONCLUSIONS: Our findings underscore the significant role of TMEM135 as a modulator in orchestrating the differentiation trajectory of BMSCs and promoting a shift in mitochondrial dynamics toward fission. This ultimately contributes to the osteogenesis process. This work has provided promising biological targets for the treatment of osteoporosis.

Overexpressing Ugp1 promotes phosphate uptake and accumulation in rice (Oryza sativa).

Plant responses to phosphate (Pi) starvation stress involve an array of adaptive strategies including enhanced accumulation and shoot-to-root transport of carbohydrates required for activating the plant Pi starvation signaling. However, the contribution of carbohydrate biosynthesis genes to maintaining phosphorus (P) homeostasis remains unknown, and the functional characterization of sugar metabolism genes is often impeded or compromised due to the loss of fertility of the null mutants. Here, a highly expressed gene encoding UDP-glucose pyrophosphorylase in rice (Oryza sativa), Ugp1, was functionally characterized. Ugp1 was transcriptionally induced in leaf blades by Pi starvation. As a link between sucrose (Suc) and P, we assumed that overexpression of Upg1 would alter the Suc concentration. Given that Suc is a signaling molecule, such concentration changes would affect the P deficiency signal transduction, thereby altering the homeostasis of endogenous P. The results showed that, overexpression of Ugp1 decreased plant biomass, increased sucrose content, and promoted Pi accumulation. The elevated Pi accumulation in Ugp1-OX plants was accompanied by the up-regulation of Pi-starvation-induced genes. Taken together, these results demonstrate that Ugp1 is a positive regulator of sucrose accumulation, and is required for maintaining P homeostasis in rice. Ugp1 thus represents a novel entry point to dissect the mechanisms underlying the carbon-P crosstalk. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01368-8.

Phosphate Transporter OsPT4, Ubiquitinated by E3 Ligase OsAIRP2, Plays a Crucial Role in Phosphorus and Nitrogen Translocation and Consumption in Germinating Seed.

Phosphorus (P) and nitrogen (N) are essential macronutrients necessary for plant growth and development. OsPT4 is a high-affinity phosphate (Pi) transporter that has a positive impact on nutrient uptake and seed development. In this study, the expression patterns of different Pi transporter genes in germinating seeds were determined, and the relative expression of OsPT4 was induced in Pi-deficient seeds and gradually increased with the passage of germination time. The analysis of P, N, Pi, and amino acid concentrations in germinating seeds of OsPT4 mutants showed that the OsPT4 mutation caused P and N retention and a continuous reduction in multiple amino acid concentrations in germinating seeds. Transcriptome analysis and qRT-PCR results also indicated that the OsPT4 mutation inhibits the expression of genes related to P and N transportation and amino acid synthesis in germinating seeds. In addition, the paraffin section and TUNEL assay of OsPT4 mutant germinating seeds suggests that OsPT4 mutation causes programmed cell death (PCD) delayed in the aleurone layer and inhibition of leaf outgrowth. Moreover, we also found that OsPT4 was ubiquitinated by OsAIRP2, which is a C3HC4-type RING E3 Ub ligase. Our studies illustrate that OsPT4 plays a crucial role in P and N collaborative translocation and consumption in germinating seeds. It also provides a theoretical basis for the molecules and physiological mechanisms of P and N cross-talk under suppressed Pi uptake conditions.

Nanofiber Composite Microchannel-Containing Injectable Hydrogels for Cartilage Tissue Regeneration.

Articular cartilage tissue is incapable of self-repair and therapies for cartilage defects are still lacking. Injectable hydrogels have drawn much attention in the field of cartilage regeneration. Herein, the novel design of nanofiber composite microchannel-containing hydrogels inspired by the tunnel-piled structure of subway tunnels is proposed. Based on the aldehydized polyethylene glycol/carboxymethyl chitosan (APA/CMCS) hydrogels, thermosensitive gelatin microrods (GMs) are used as a pore-forming agent, and coaxial electrospinning polylactic acid/gelatin fibers (PGFs) loaded with kartogenin (KGN) are used as a reinforcing agent and a drug delivery system to construct the nanofiber composite microchannel-containing injectable hydrogels (APA/CMCS/KGN@PGF/GM hydrogels). The in situ formation, micromorphology and porosity, swelling and degradation, mechanical properties, self-healing behavior, as well as drug release of the nanofiber composite microchannel-containing hydrogels are investigated. The hydrogel exhibits good self-healing ability, and the introduction of PGF nanofibers can significantly improve the mechanical properties. The drug delivery system can realize sustained release of KGN to match the process of cartilage repair. The microchannel structure effectively promotes bone marrow mesenchymal stem cell (BMSC) proliferation and ingrowth within the hydrogels. In vitro and animal experiments indicate that the APA/CMCS/KGN@PGF/GM hydrogels can enhance the chondrogenesis of BMSCs and promote neocartilage formation in the rabbit cartilage defect model.

Potassium transporter OsHAK18 mediates potassium and sodium circulation and sugar translocation in rice.

High-affinity potassium (K+) transporter (HAK)/K+ uptake permease (KUP)/K+ transporter (KT) have been identified in all genome-sequenced terrestrial plants. They play an important role in K+ acquisition and translocation and in enhancing salt tolerance. Here, we report that plasma membrane-located OsHAK18 functions in K+ and sodium (Na+) circulation and sugar translocation in rice (Oryza sativa). OsHAK18 was expressed mainly, though not exclusively, in vascular tissues and particularly in the phloem. Knockout (KO) of OsHAK18 reduced K+ concentration in phloem sap and roots but increased K+ accumulation in the shoot of both 'Nipponbare' and 'Zhonghua11' cultivars, while overexpression (OX) of OsHAK18 driven by its endogenous promoter increased K+ concentration in phloem sap and roots and promoted Na+ retrieval from the shoot to the root under salt stress. Split-root experimental analysis of rubidium (Rb+) uptake and circulation indicated that OsHAK18-OX promoted Rb+ translocation from the shoot to the root. In addition, OsHAK18-KO increased while OsHAK18-OX reduced soluble sugar content in the shoot and oppositely affected the sugar concentration in the phloem and its content in the root. Moreover, OsHAK18-OX dramatically increased grain yield and physiological K+ utilization efficiency. Our results suggest that-unlike other OsHAKs analyzed heretofore-OsHAK18 is critical for K+ and Na+ recirculation from the shoot to the root and enhances the source-to-sink translocation of photo-assimilates.