An improved CRISPR and CRISPR interference (CRISPRi) toolkit for engineering the model methanogenic archaeon Methanococcus maripaludis.

BACKGROUND: The type II based CRISPR-Cas system remains restrictedly utilized in archaea, a featured domain of life that ranks parallelly with Bacteria and Eukaryotes. Methanococcus maripaludis, known for rapid growth and genetic tractability, serves as an exemplary model for studying archaeal biology and exploring CO2-based biotechnological applications. However, tools for controlled gene regulation remain deficient and CRISPR-Cas tools still need improved in this archaeon, limiting its application as an archaeal model cellular factory. RESULTS: This study not only improved the CRISPR-Cas9 system for optimizing multiplex genome editing and CRISPR plasmid construction efficiencies but also pioneered an effective CRISPR interference (CRISPRi) system for controlled gene regulation in M. maripaludis. We developed two novel strategies for balanced expression of multiple sgRNAs, facilitating efficient multiplex genome editing. We also engineered a strain expressing Cas9 genomically, which simplified the CRISPR plasmid construction and facilitated more efficient genome modifications, including markerless and scarless gene knock-in. Importantly, we established a CRISPRi system using catalytic inactive dCas9, achieving up to 100-fold repression on target gene. Here, sgRNAs targeting near and downstream regions of the transcription start site and the 5'end ORF achieved the highest repression efficacy. Furthermore, we developed an inducible CRISPRi-dCas9 system based on TetR/tetO platform. This facilitated the inducible gene repression, especially for essential genes. CONCLUSIONS: Therefore, these advancements not only expand the toolkit for genetic manipulation but also bridge methodological gaps for controlled gene regulation, especially for essential genes, in M. maripaludis. The robust toolkit developed here paves the way for applying M. maripaludis as a vital model archaeal cell factory, facilitating fundamental biological studies and applied biotechnology development of archaea.

In-situ nanoplatform with synergistic neutrophil intervention and chemotherapy to prevent postoperative tumor recurrence and metastasis.

In addition to residual tumor cells, surgery-induced inflammation significantly contributes to tumor recurrence and metastasis by recruiting polymorphonuclear neutrophils (PMNs) and promoting their involvement in tumor cell proliferation, invasion and immune evasion. Efficiently eliminating residual tumor cells while concurrently intervening in PMN function represents a promising approach for enhanced postoperative cancer treatment. Here, a chitosan/polyethylene oxide electrospun fibrous scaffold co-delivering celecoxib (CEL) and doxorubicin-loaded tumor cell-derived microparticles (DOX-MPs) is developed for postoperative in-situ treatment in breast cancer. This implant (CEL/DOX-MPs@CP) ensures prolonged drug retention and sustained release within the surgical tumor cavity. The released DOX-MPs effectively eliminate residual tumor cells, while the released CEL inhibits the function of inflammatory PMNs, suppressing their promotion of residual tumor cell proliferation, migration and invasion, as well as remodeling the tumor immune microenvironment. Importantly, the strategy is closely associated with interference in neutrophil extracellular trap (NET) released from inflammatory PMNs, leading to a substantial reduction in postoperative tumor recurrence and metastasis. Our results demonstrate that CEL/DOX-MPs@CP holds great promise as an implant to enhance the prognosis of breast cancer patients following surgery.

Ice Nucleation Mechanisms on Platinum Surfaces in PEM Fuel Cells: Effects of Surface Morphology and Wettability.

Understanding the ice nucleation mechanism in the catalyst layers (CLs) of proton exchange membrane (PEM) fuel cells and inhibiting icing by designing the CLs can optimize the cold start strategies, which can enhance the performance of PEM fuel cells. Herein, mitigating the structural matching and templating effects by adjusting the surface morphology and wettability can inhibit icing on the platinum (Pt) catalyst surface effectively. The Pt(211) surface can inhibit icing because the atomic spacing of (211) crystalline surface is much larger than the characteristic distance of ice crystal, thereby mitigating the structural matching effects. A water overlayer on the Pt surface induced by the strong attraction of Pt can act as a template for ice layers and plays an important role in the icing process. Buckling of water overlayer due to the larger atomic spacing of (211) crystalline surface mitigates the templating effect and inhibits icing. Moreover, the water overlayer on the hydrophobic Pt(211) surface with fewer water molecules also mitigates the templating effect, which makes ice nucleation more difficult than homogeneous nucleation. These findings reveal the ice nucleation mechanisms on the Pt catalyst surface from the molecular level and are valuable for catalyst designs to inhibit icing in CL.

Continuous polyamorphic transition in high-entropy metallic glass.

Polyamorphic transition (PT) is a compelling and pivotal physical phenomenon in the field of glass and materials science. Understanding this transition is of scientific and technological significance, as it offers an important pathway for effectively tuning the structure and property of glasses. In contrast to the PT observed in conventional metallic glasses (MGs), which typically exhibit a pronounced first-order nature, herein we report a continuous PT (CPT) without first-order characteristics in high-entropy MGs (HEMGs) upon heating. This CPT behavior is featured by the continuous structural evolution at the atomic level and an increasing chemical concentration gradient with temperature, but no abrupt reduction in volume and energy. The continuous transformation is associated with the absence of local favorable structures and chemical heterogeneity caused by the high configurational entropy, which limits the distance and frequency of atomic diffusion. As a result of the CPT, numerous glass states can be generated, which provides an opportunity to understand the nature, atomic packing, formability, and properties of MGs. Moreover, this discovery highlights the implication of configurational entropy in exploring polyamorphic glasses with an identical composition but highly tunable structures and properties.

The ß-d-manno-heptoses are immune agonists across kingdoms.

Bacterial small molecule metabolites such as adenosine-diphosphate-d-glycero-ß-d-manno-heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We show that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea, eukaryotes, and viruses. We identified a conserved STTR5 motif as a hallmark of heptose nucleotidyltransferases that can synthesize not only ADP-heptose but also cytidine-diphosphate (CDP)- and uridine-diphosphate (UDP)-heptose. Both CDP- and UDP-heptoses are agonists that trigger stronger alpha-protein kinase 1 (ALPK1)-dependent immune responses than ADP-heptose in human and mouse cells and mice. We also produced ADP-heptose in archaea and verified its innate immune agonist functions. Hence, the ß-d-manno-heptoses are cross-kingdom, small-molecule, pathogen-associated molecular patterns that activate the ALPK1-dependent innate immune signaling cascade.

Contribution to energy conservation and quality improvement of frozen pork via contact/contactless immersion freezing in NaCl solution.

High energy consumption and quality deterioration are major challenges in the meat freezing process. In this study, the energy consumption and qualities of frozen pork were investigated using three freezing methods: nonpackaged pork air freezing (NAF), contactless immersion freezing (PIF) and contact immersion freezing (NIF) with NaCl solution as a refrigerant. The results indicated that NIF could improve the energy conservation and freezing efficiency in >4 freezing treatment-times by increasing the unfrozen water content, decreasing the frozen heat load, shortening the freezing time and reducing evaporation loss. NIF could also increase the a* value of the pork and improve the water-holding capacity by facilitating the conversion of free water to immobilized-water. The two immersion freezing methods could reduce freezing-thawing loss and protein loss by alleviating muscle tissue freezing damage. These results provide a suitable application of immersion freezing with energy conservation, high efficiency and good quality of frozen-pork.

[Identification of novel genetic loci associated with major depressive disorder and the hippocampus in a European population using the condFDR method].

OBJECTIVE: To identify additional loci associated with depression and the hippocampus (HIP) through genome-wide association study. METHODS: The depression-related genome-wide association study (GWAS) meta summary data was downloaded from the official website of the Psychiatric Genomics Consortium, which had involved 170 756 cases and 329 443 controls. The left and right hippocampal volume GWAS data sets were downloaded from the UK Biobank, which involved 33 224 participants. The conditional false discovery rate (condFDR) was used to identify novel genetic loci for depression and left and right hippocampal volumes, and a conjunctional false discovery rate (conjFDR) was used to evaluate the enrichment of pleiotropic loci between depression and left and right hippocampal volumes. RESULTS: Respectively, 7, 13, and 12 new loci have been associated with depression, left hippocampal volume and right hippocampal volume, with a significant threshold of condFDR < 0.01. A site of rs1267073 locus was found to be shared by the depression and right hippocampal volume with a threshold of conjFDR < 0.01. CONCLUSION: Above findings have provided more insights into the genetic mechanisms underlying the volume of hippocampus and the risk for depression. The results may also provide evidence for future clinical trials for treating depression.

An in-situ biochar-enhanced anaerobic membrane bioreactor for swine wastewater treatment under various organic loading rates.

A biochar-assisted anaerobic membrane bioreactor (BC-AnMBR) was conducted to evaluate the performance in treating swine wastewater with different organic loading rates (OLR) ranging from 0.38 to 1.13 kg-COD/(m3.d). Results indicated that adding spent coffee grounds biochar (SCG-BC) improved the organic removal efficiency compared to the conventional AnMBR, with an overall COD removal rate of > 95.01%. Meanwhile, methane production of up to 0.22 LCH4/gCOD with an improvement of 45.45% was achieved under a high OLR of 1.13 kg-COD/(m3.d). Furthermore, the transmembrane pressure (TMP) in the BC-AnMBR system was stable at 4.5 kPa, and no irreversible membrane fouling occurred within 125 days. Microbial community analysis revealed that the addition of SCG-BC increased the relative abundance of autotrophic methanogenic archaea, particularly Methanosarcina (from 0.11% to 11.16%) and Methanothrix (from 16.34% to 24.05%). More importantly, Desulfobacterota and Firmicutes phylum with direct interspecific electron transfer (DIET) capabilities were also enriched with autotrophic methanogens. Analysis of the electron transfer pathway showed that the concentration of c-type cytochromes increased by 38.60% in the presence of SCG-BC, and thus facilitated the establishment of DIET and maintained high activity of the electron transfer system even at high OLR. In short, the BC-AnMBR system performs well under various OLR conditions and is stable in the recovery energy system for swine wastewater.

Isocucurbitacin B inhibits glioma growth through PI3K/AKT pathways and increases glioma sensitivity to TMZ by inhibiting hsa-mir-1286a.

Aim: Glioma accounts for 81% of all cancers of the nervous system cancers and presents one of the most drug-resistant malignancies, resulting in a relatively high mortality rate. Despite extensive efforts, the complete treatment options for glioma remain elusive. The effect of isocucurbitacin B (isocuB), a natural compound extracted from melon pedicels, on glioma has not been investigated. This study aims to investigate the inhibitory effect of isocuB on glioma and elucidate its underlying mechanisms, with the objective of developing it as a potential therapeutic agent for glioma. Methods: We used network pharmacology and bioinformatics analysis to predict potential targets and associated pathways of isocuB in glioma. Subsequently, the inhibitory effect of isocuB on glioma and its related mechanisms were assessed through Counting Kit-8 (CCK-8), wound healing, transwell, Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and other in vitro experiments, alongside tumor formation experiments in nude mice. Results: Based on this investigation, it suggested that isocuB might inhibit the growth of gliomas through the PI3K-AKT and MAPK pathways. Additionally, we proposed that isocuB may enhance glioma drug sensitivity to temozolomide (TMZ) via modulation of hsa-mir-1286a. The CCK-8 assay revealed that isocuB exhibited inhibitory effects on U251 and U87 proliferation and outperformed TMZ. Wound healing and transwell experiments showed that isocuB inhibited the invasion and migration of U251 cells by suppressing the activity of MMP-2/9, N-cadherin, and Vimentin. The TdT-mediated dUTP-biotin nick end labeling (TUNEL) and flow cytometry (FCM) assays revealed that isocuB induced cell apoptosis through inhibition of BCL-2. Subsequently, we conducted RT-qPCR and WB experiments, which revealed that PI3K/AKT and MAPK pathways might be involved in the mechanism of the inhibition isocuB on glioma. Additionally, isocuB promoted the sensitivity of glioma U251 to TMZ by inhibiting hsa-mir-1286a. Furthermore, we constructed TMZ-resistant U251 strains and demonstrated effective inhibition by isocuB against these resistant strains. Finally, we confirmed that isocuB can inhibit tumor growth in vivo through experiments on tumors in nude mice. Conclusion: IsocuB may protect against glioma by acting on the PI3K/AKT and MAPK pathways and promote the sensitivity of glioma U251 to TMZ by inhibiting hsa-mir-1286a.

Advancing presurgical non-invasive molecular subgroup prediction in medulloblastoma using artificial intelligence and MRI signatures.

Global investigation of medulloblastoma has been hindered by the widespread inaccessibility of molecular subgroup testing and paucity of data. To bridge this gap, we established an international molecularly characterized database encompassing 934 medulloblastoma patients from thirteen centers across China and the United States. We demonstrate how image-based machine learning strategies have the potential to create an alternative pathway for non-invasive, presurgical, and low-cost molecular subgroup prediction in the clinical management of medulloblastoma. Our robust validation strategies-including cross-validation, external validation, and consecutive validation-demonstrate the model's efficacy as a generalizable molecular diagnosis classifier. The detailed analysis of MRI characteristics replenishes the understanding of medulloblastoma through a nuanced radiographic lens. Additionally, comparisons between East Asia and North America subsets highlight critical management implications. We made this comprehensive dataset, which includes MRI signatures, clinicopathological features, treatment variables, and survival data, publicly available to advance global medulloblastoma research.

The chromosome level whole genome sequence and the seconary matabolism gene cluster prediction of Fusarium meridionale, the pathogen causing maize ear rot.

Fusarium meridionale is one of the pathogens causing maize ear rot, it produce bioactive secondary metabolites may threaten humans food safty, however, the production mechanism of the secondary metabolites and their interaction with maize ear remains poorly understood. To facilitate related studies, we sequenced and assembled the genome of F. meridionale strain JX18-4. The size of F. meridionale JX18-4 genome is 37.11 Mbp, include four nuclear chromosome contigs that consists of 11920 coding genes and one mitochondrial contig. 95.64% gene synteny collinearity was found between the assembly and the reference genomes F. graminearum strain PH-1. Compared to the sequences of seconary matabolism gene clusters sequences reported previously, the stain JX18-4 was predicted potential producing 8 clusters, including nivalenol, zearalenone, aurofusarin, fusarielin, fusaristatin A, fusarin, fusarubin and butenolide. This study aims to reveal the molecular mechanism of secondary metabolites producing, and the genomic information of JX18-4 will provide resources for the study of biological control mechanisms and plant-microbe interactions.

Effects of aerobic exercise on myocardial injury, NF-B expression, glucolipid metabolism and inflammatory factors in rats with coronary heart disease.

OBJECTIVE: To investigate the influence of aerobic exercise on myocardial injury, NF-B expression, glucolipid metabolism and inflammatory factors in rats with Coronary Heart Disease (CHD) and explore the possible causative role. METHODS: 45 Sprague Dawley® rats were randomized into model, control and experimental groups. A high-fat diet was adopted for generating a rat CHD model, and the experimental group was given a 4-week aerobic exercise intervention. ECG was utilized to evaluate the cardiac function of the rats; HE staining to evaluate the damage of myocardial tissue; TUNEL staining to evaluate cardiomyocyte apoptosis level; ELISA to assay the contents of inflammatory factors and glucolipid metabolism in cardiomyocytes; qPCR to assay IB- and NF-B mRNA expression; Western-blot to assay the apoptosis-related proteins and NF-B signaling pathway-related proteins expressions in myocardial tissue. RESULTS: In contrast to the model group, aerobic exercise strongly improved the rat's cardiac function and glucolipid metabolism (p < 0.01), enhanced IL-10 content, Bcl-2/Bax level as well as IB- protein and mRNA expression (p < 0.01), and reduced myocardial injury and cardiomyocyte apoptosis, the contents of IL-6, IL-1 and TNF-, Caspase 3 level, NF-B mRNA and protein expression and p-p38 and p-STAT3 expressions (p < 0.01). CONCLUSION: Aerobic exercise can not only effectively reduce myocardial injury, the release of inflammatory factors and NF-B expression in CHD rats, but also improve cardiac function and glucolipid metabolism. Its mechanism is likely to be related to the inhibition of the NF-B signaling pathway.

Bu zhong Yiqi Decoction ameliorates mild cognitive impairment by improving mitochondrial oxidative stress damage via the SIRT3/MnSOD/OGG1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-Zhong-Yi-Qi Decoction(BZYQD) is a traditional formula commonly used in China, known for its effects in tonifying Qi and raising Yang. It can relieve symptoms of cognitive impairment such as forgetfulness and lack of concentration caused by qi deficiency, which is common in aging and debilitating. However, much of the current research on BZYQD has been focused on its impact on the digestive system, leaving its molecular mechanisms in improving cognitive function largely unexplored. AIM OF THE STUDY: Cognitive decline in the aging central nervous system is intrinsically linked to oxidative damage. This study aims to investigate the therapeutic mechanism of BZYQD in treating mild cognitive impairment caused by qi deficiency, particularly through repair of mitochondrial oxidative damage. MATERIALS AND METHODS: A rat model of mild cognitive impairment (MCI) was established by administering reserpine subcutaneously for two weeks, followed by a two-week treatment with BZYQD/GBE. In vitro experiments were conducted to assess the effects of BZYQD on neuronal cells using a H2O2-induced oxidative damage model in PC12 cells. The open field test and the Morris water maze test evaluated the cognitive and learning memory abilities of the rats. HE staining and TEM were employed to observe morphological changes in the hippocampus and its mitochondria. Mitochondrial activity, ATP levels, and cellular viability were measured using assay kits. Protein expression in the SIRT3/MnSOD/OGG1 pathway was analyzed in tissues and cells through western blotting. Levels of 8-OH-dG in mitochondria extracted from tissues and cells were quantified using ELISA. Mitochondrial morphology in PC12 cells was visualized using Mito Red, and mitochondrial membrane potential was assessed using the JC-1 kit. RESULTS: BZYQD treatment significantly improved cognitive decline caused by reserpine in rats, as well as enhanced mitochondrial morphology and function in the hippocampus. Our findings indicate that BZYQD mitigates mtDNA oxidative damage in rats by modulating the SIRT3/MnSOD/OGG1 pathway. In PC12 cells, BZYQD reduced oxidative damage to mitochondria and mtDNA in H2O2-induced conditions and was associated with changes in the SIRT3/MnSOD/OGG1 pathway. CONCLUSION: BZYQD effectively counteracts reserpine-induced mild cognitive impairment and ameliorates mitochondrial oxidative stress damage through the SIRT3/MnSOD/OGG1 pathway.

SCB-YOLOv5: a lightweight intelligent detection model for athletes' normative movements.

Intelligent detection of athlete behavior is beneficial for guiding sports instruction. Existing mature target detection algorithms provide significant support for this task. However, large-scale target detection algorithms often encounter more challenges in practical application scenarios. We propose SCB-YOLOv5, to detect standardized movements of gymnasts. First, the movements of aerobics athletes were captured, labeled using the labelImg software, and utilized to establish the athlete normative behavior dataset, which was then enhanced by the dataset augmentation using Mosaic9. Then, we improved the YOLOv5 by (1) incorporating the structures of ShuffleNet V2 and convolutional block attention module to reconstruct the Backbone, effectively reducing the parameter size while maintaining network feature extraction capability; (2) adding a weighted bidirectional feature pyramid network into the multiscale feature fusion, to acquire precise channel and positional information through the global receptive field of feature maps. Finally, SCB-YOLOv5 was lighter by 56.9% than YOLOv5. The detection precision is 93.7%, with a recall of 99% and mAP value of 94.23%. This represents a 3.53% improvement compared to the original algorithm. Extensive experiments have verified that our method. SCB-YOLOv5 can meet the requirements for on-site athlete action detection. Our code and models are available at https://github.com/qingDu1/SCB-YOLOv5 .

Discovery, biosynthesis, organic synthesis, and bioactivities of meroterpenoids from Rhododendron species.

Meroterpenoids discovered in Rhododendrons species possess unique chemical structures and biological activities and are expected to become new drug targets for Alzheimer's disease, metabolic disorders, and chronic kidney disease, and these compounds have attracted increasing attention in recent years. In this study, Rhododendron meroterpenoids and their structures, classifications, racemate distribution, biosynthetic pathways, chemical synthesis, and bioactivities are reviewed prior to 2023.

Characteristics and Differences in Mpox Patients with and without HIV Infection: A Retrospective Cross-Sectional Study in Chengdu, China.

Purpose: To date, there are few reports about mpox case series in China, and scarce information is available about the in-vivo kinetics of T-cell responses in the early stage of mpox infection. This study aims to investigate the clinical difference among mpox patients with and without human immunodeficiency virus (HIV) infection. Patients and Methods: A total of 56 patients diagnosed with mpox by Chengdu Center for Disease Control and Prevention (CDC) and hospitalized in Public Health Clinical Center of Chengdu were retrospectively included and divided into an HIV-infected group (n=23) and a non-HIV-infected group (n=33). Clinical characteristics and serum chemistry findings of mpox patients were collected in order to analyze the differences between the HIV-infected group and the non-HIV-infected group. Results: Multiple laboratory abnormalities, including elevated C-reactive protein (69.1%), hypocalcemia (50.9%), elevated CD3+CD8+T counts (47.0%) and inverted ratio of CD3+CD4+T to CD3+CD8+T (64.7%) were common in mpox cases. There were statistically significant differences (all P < 0.05) in age, serum calcium levels, CD3+CD4+T counts, the ratio of CD3+CD4+T to CD3+CD8+T, proportion with >10 rashes, incidence of proctitis anus and time from rash growth to rash scab shedding between HIV-infected group and non-HIV-infected group. In the early stage of mpox infection, the median of CD3+CD8+T counts in the non-HIV-infected group was significantly higher than that in healthy donors (P<0.001), and the median of CD3+CD4+T/CD3+CD8+T ratio was significantly lower (P<0.001). The median of CD3+CD4+T counts in mpox patients co-infected with HIV significantly decreased compared to the pre-infection level (p =0.033). Conclusion: Our study indicates that mpox co-infected with HIV patients have longer lasting rash lesions and a higher incidence of proctitis anus. T-cell responses may be different between HIV-infected and non-HIV-infected individuals in the early stage of mpox infection.

Regioselectivity Switch of α-Amino Acid-Derived Esters and MBH Carbonates for the Synthesis of Allyl-Substituted Azlactones.

Allylic azlactones are greatly significant in terms of potential bioactivities and synthetic applications. Owing to the burgeoning interest of the pharmaceutical industry in α-amino acid derivatives, discovering strategies for the synthesis of allylic azlactones is important. Herein, we establish a transition-metal-free regioselectivity switch of α-amino acid-derived esters and MBH carbonates, which exhibits broad reaction scope and good reaction yields. Control reactions indicate that both base and solvent are important for regioselectivity.

Virtual Reality Therapy for the Management of Chronic Spinal Pain: Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness of virtual reality (VR) therapy in adults with chronic spinal pain (CSP) is unclear. OBJECTIVE: This study was conducted to compare the effectiveness of VR therapy and other therapies in adults with CSP, especially patients with inflammation-related pain. METHODS: PubMed, Web of Science, Cochrane Library, Embase, and CINAHL databases were searched up to November 11, 2023. Randomized controlled trials (RCTs) comparing adults with CSP receiving VR therapy with those receiving other therapies were included. The trial registration platform as well as the reference lists of included studies and previous systematic reviews and meta-analyses were manually searched. Two independent reviewers performed study selection, data extraction, risk-of-bias assessment, and evaluation of the quality of the evidence. The weighted mean difference (WMD) was used as the effect size used to synthesize the outcome measure. RESULTS: In total, 16 RCTs involving 800 participants were included in this meta-analysis. The pooled data from 15 (94%) RCTs including 776 (97%) participants showed that VR therapy was superior in improving pain intensity (WMD=-1.63, 95% CI -2.11 to -1.16, P<.001, I2=90%) and reducing inflammatory markers, including C-reactive protein (WMD=-0.89, 95% CI -1.07 to -0.70, P<.001, I2=0%), tumor necrosis factor-alpha (WMD=-6.60, 95% CI -8.56 to -4.64, P<.001, I2=98%), and interleukin-6 (WMD=-2.76, 95% CI -2.98 to -2.53, P<.001, I2=0%). However, no significant differences were found in terms of the spinal range of motion (ROM), disability level, or fear of movement. In addition, 10 (63%) of the included RCTs had a high risk of bias. CONCLUSIONS: VR therapy may be an effective and safe intervention for reducing symptoms in patients with CSP, as it is shown to exert significant analgesic effects and beneficial improvements in inflammatory factor levels. However, this approach may not have significant effects on the spinal ROM, disability level, or fear of movement. Notably, the quality of the evidence from the RCTs included in this study ranged from moderate to low. Therefore, we recommend that readers interpret the results of this study with caution. TRIAL REGISTRATION: PROSPERO CRD42022382331; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=382331.