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Autophagy is a highly conserved catabolic process and participates in a variety of cellular biological activities. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, as a critical regulator of autophagy, is involved in the initiation and promotion of a series of pathological disorders including various tumors. Autophagy also participates in regulating the balance between the tumor and the tumor microenvironment. Natural products have been considered a treasure of new drug discoveries and are of great value to medicine. Mounting evidence has suggested that numerous natural products are targeting PI3K/AKT/mTOR-mediated autophagy, thereby suppressing tumor growth. Furthermore, autophagy plays a “double-edged sword” role in different tumors. Targeting PI3K/AKT/mTOR-mediated autophagy is an important therapeutic strategy for a variety of tumors, and plays important roles in enhancing the chemosensitivity of tumor cells and avoiding drug resistance. Therefore, we summarized the roles of PI3K/AKT/mTOR-mediated autophagy in tumorigenesis, progression, and drug resistance of tumors, which may be utilized to design preferably therapeutic strategies for various tumors.

Non-specific adsorption (NSA) is a persistent problem that negatively affects biosensors, decreasing sensitivity, specificity, and reproducibility. Passive and active removal methods exist to remedy this issue, by coating the surface or generating surface forces to shear away weakly adhered biomolecules, respectively. However, many surface coatings are not compatible or effective for sensing, and thus active removal methods have been developed to combat this phenomenon. This review aims to provide an overview of methods of NSA reduction in biosensing, focusing on the shift from passive methods to active methods in the past decade. Attention is focused on protein NSA, due to their common use in biosensing for biomarker diagnostics. To our knowledge, this is the first review to comprehensively discuss active NSA removal methods. Lastly, the challenges and future perspectives of NSA reduction in biosensing are discussed.

Background: Lumbar muscle dysfunction due to pain might be related to altered lumbar muscle structure. Macroscopically, muscle degeneration in low back pain (LBP) is characterized by a decrease in cross-sectional area and an increase in fat infiltration in the lumbar paraspinal muscles. In addition microscopic changes, such as changes in fiber distribution, might occur. Inconsistencies in results from different studies make it difficult to draw firm conclusions on which structural changes are present in the different types of non-specific LBP. Insights regarding structural muscle alterations in LBP are, however, important for prevention and treatment of non-specific LBP. Objective: The goal of this article is to review which macro- and/or microscopic structural alterations of the lumbar muscles occur in case of non-specific chronic low back pain (CLBP), recurrent low back pain (RLBP), and acute low back pain (ALBP). Study Design: Systematic review. Setting: All selected studies were case-control studies. Methods: A systematic literature search was conducted in the databases PubMed and Web of Science. Only full texts of original studies regarding structural alterations (atrophy, fat infiltration, and fiber type distribution) in lumbar muscles of patients with non-specific LBP compared to healthy controls were included. All included articles were scored on methodological quality. Results: Fifteen studies were found eligible after screening title, abstract, and full text for inclusion and exclusion criteria. In CLBP, moderate evidence of atrophy was found in the multifidus; whereas, results in the paraspinal and the erector spinae muscle remain inconclusive. Also moderate evidence occurred in RLBP and ALBP, where no atrophy was shown in any lumbar muscle. Conflicting results were seen in undefined LBP groups. Results concerning fat infiltration were inconsistent in CLBP. On the other hand, there is moderate evidence in RLBP that fat infiltration does not occur, although a larger muscle fat index was found in the erector spinae, multifidus, and paraspinal muscles, reflecting an increased relative amount of intramuscular lipids in RLBP. However, no studies were found investigating fat infiltration in ALBP. Restricted evidence indicates no abnormalities in fiber type in the paraspinal muscles in CLBP. No studies have examined fiber type in ALBP and RLBP. Limitations: Lack of clarity concerning patient definitions, exact LBP symptoms, and applied methods. Conclusions: The results indicate atrophy in CLBP in the multifidus and paraspinal muscles but not in the erector spinae. No atrophy was shown in RLBP and ALBP. Fat infiltration did not occur in RLBP, but results in CLBP were inconsistent. No abnormalities in fiber type in the paraspinal muscles were found in CLBP. Key words: Low back pain, non-specific, chronic, recurrent, acute, muscle structure, fat infiltration, cross-sectional area, fiber type, review

Extracellular nucleotides (e.g., ATP, ADP, UTP, UDP) released by inflammatory cells interact with specific purinergic P2 type receptors to modulate their recruitment and activation. The focus of this review is on stimuli and mechanisms of extracellular nucleotide release and its consequences during inflammation. Necrosis leads to non-specific release of nucleotides, whereas specific release mechanisms include vesicular exocytosis and channel-mediated release via connexin or pannexin hemichannels. These release mechanisms allow stimulated inflammatory cells such as macrophages, neutrophils, and endothelial cells to fine-tune autocrine/paracrine responses during acute and chronic inflammation. Key effector functions of inflammatory cells are therefore regulated by purinergic signaling in acute and chronic diseases, making extracellular nucleotide release a promising target for the development of new therapies.

The resistance of zwitterionic polymer coatings against the adsorption of proteins and the attachment of pathogenic bacteria is influenced by the precise molecular architecture of the polymers. Two until now rarely studied molecular variables in this context are side chain spacer groups separating the zwitterionic moieties from the polymer backbone and spacer groups separating the cationic and anionic groups within the zwitterionic moiety. Therefore, a set of six poly(sulfobetaine)s and poly(sulfabetaine)s is prepared, in which these spacer groups are systematically varied, incorporating ethylene, propylene, and undecylene side chain spacers, as well as ethylene, propylene, and butylene inter‐charge spacers, and their effects on the antifouling behavior are explored. Hence, the corresponding zwitterionic methacrylates are copolymerized with a photo‐reactive methacrylate bearing a benzophenone moiety. All zwitterionic coatings reveal hydrophilic properties when immersed in water and those with relatively short spacers show effective suppression of non‐specific protein adsorption. Polysulfobetaines outperform the polysulfabetaine ones in terms of resistance against adhesion of bacteria. The overall best fouling protection is observed for the polysulfobetaine bearing a propylene side chain spacer, which coincides with their relatively highest water solubility. The results corroborate previous findings that even apparently minor molecular changes of polyzwitterions can strongly affect their antifouling performance. Hydrophilic sulfobetaine‐based polymers with relatively short inter‐charges and side‐chain spacers outperform analogous sulfabetaines in terms of bacterial fouling resistance. An extended undecyl side‐chain spacer results in increased hydrophobicity in the air but retains rapid reorientation and hydrophilicity underwater, whereby the resistance to proteins and bacterial accumulation is partially compromised.

INTRODUCTION Accurate identification of individuals at risk for cognitive decline is critical for treatment planning and trial enrichment strategies. We evaluated the combined utility of plasma phosphorylated tau at threonine 217 (p‐tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in predicting domain‐specific cognitive decline. METHODS Participants (n = 523; 40.9% cognitively unimpaired [CU]; 59.1% mild cognitive impairment [MCI]) were from the Massachusetts Alzheimer's Disease Research Center. Cognition was assessed using the National Alzheimer's Coordinating Center Uniform Data Set. Participants were classified as high(+)/low(−) for each biomarker using Gaussian mixture models. RESULTS Among all participants, high p‐tau217 alone [p‐tau217(+)NfL(–)GFAP(–)] was associated with a steeper decline in episodic/semantic memory and processing speed compared to the all‐low group (p ≤ 0.02). With the addition of high GFAP [p‐tau217(+)NfL(–)GFAP(+)], steeper decline extended to most cognitive domains, including global cognition and executive function, compared to the all‐low group. In CU, faster decline in global cognition and executive function was seen when all biomarkers were elevated ([p‐tau217(+)NfL(+)GFAP(+)]; p ≤ 0.04). DISCUSSION Combined plasma biomarkers predict decline in cognitive domains vulnerable to early disease. Highlights High phosphorylated tau at threonine 217 (p‐tau217) alone was associated with declines in semantic/episodic memory, whereas its combination with elevated glial fibrillary acidic protein (GFAP) predicted declines in a wider range of cognitive domains. Elevated neurofilament light chain (NfL) amplifies the cognitive decline already driven by p‐tau217 and GFAP. In cognitively unimpaired individuals, subtle domain‐specific cognitive declines can be detected when both core and non‐core Alzheimer's disease biomarkers are used. Our finding highlights the importance of focusing on vulnerable cognitive domains during early disease where global cognition may appear stable but specific impairments can be masked within composite scores.

Purpose Inconsistent reporting of outcomes in clinical trials of patients with non-specific low back pain (NSLBP) hinders comparison of findings and the reliability of systematic reviews. A core outcome set (COS) can address this issue as it defines a minimum set of outcomes that should be reported in all clinical trials. In 1998, Deyo et al. recommended a standardized set of outcomes for LBP clinical research. The aim of this study was to update these recommendations by determining which outcome domains should be included in a COS for clinical trials in NSLBP. Methods An International Steering Committee established the methodology to develop this COS. The OMERACT Filter 2.0 framework was used to draw a list of potential core domains that were presented in a Delphi study. Researchers, care providers and patients were invited to participate in three Delphi rounds and were asked to judge which domains were core. A priori criteria for consensus were established before each round and were analysed together with arguments provided by panellists on importance, overlap, aggregation and/or addition of potential core domains. The Steering Committee discussed the final results and made final decisions. Results A set of 280 experts was invited to participate in the Delphi; response rates in the three rounds were 52, 50 and 45 %. Of 41 potential core domains presented in the first round, 13 had sufficient support to be presented for rating in the third round. Overall consensus was reached for the inclusion of three domains in this COS: ‘physical functioning’, ‘pain intensity’ and ‘health-related quality of life’. Consensus on ‘physical functioning’ and ‘pain intensity’ was consistent across all stakeholders, ‘health-related quality of life’ was not supported by the patients, and all the other domains were not supported by two or more groups of stakeholders. Weighting all possible argumentations, the Steering Committee decided to include in the COS the three domains that reached overall consensus and the domain ‘number of deaths’. Conclusions The following outcome domains were included in this updated COS: ‘physical functioning’, ‘pain intensity’, ‘health-related quality of life’ and ‘number of deaths’. The next step for the development of this COS will be to determine which measurement instruments best measure these domains.

Immunoassays (IAs) with fluorescence-based detection are already well-established commercialized biosensing methods, such as enzyme-linked immunosorbent assay (ELISA) and lateral flow immunoassay (LFIA). Immunoassays with surface-enhanced Raman spectroscopy (SERS) detection have received significant attention from the research community for at least two decades, but so far they still lack a wide clinical commercial application. This review, unlike any other review that we have seen, performs a three-dimensional performance comparison of SERS IAs vs. fluorescence IAs. First, we compared the limit of detection (LOD) as a key performance parameter for 30 fluorescence and 30 SERS-based immunoassays reported in the literature. We also compared the clinical performances of a smaller number of available reports for SERS vs. fluorescence immunoassays (FIAs). We found that the median and geometric average LODs are about 1.5–2 orders of magnitude lower for SERS-based immunoassays in comparison to fluorescence-based immunoassays. For instance, the median LOD for SERS IA is 4.3 × 10−13 M, whereas for FIA, it is 1.5 × 10−11 M. However, there is no significant difference in average relative standard deviation (RSD)—both are about 5–6%. The analysis of sensitivity, selectivity, and accuracy reported for a limited number of the published clinical studies with SERS IA and FIA demonstrates an advantage of SERS IA over FIA, at least in terms of the median value for all three of those parameters. We discussed common and specific challenges to the performances of both SERS IA and FIA, while proposing some solutions to mitigate those challenges for both techniques. These challenges include non-specific protein binding, non-specific interactions in the immunoassays, sometimes insufficient reproducibility, relatively long assay times, photobleaching, etc. Overall, this review may be useful for a large number of researchers who would like to use immunoassays, but particularly for those who would like to make improvements and move forward in both SERS-based IAs and fluorescence-based IAs.

Background Non-specific neck (NNP) and low back pain (NLBP) pose significant global health challenges. Current treatment options often result in insufficient outcomes, either due to limited efficacy or adverse side effects. This two-center, randomized, sham-controlled trial utilized functional near-infrared spectroscopy (fNIRS) to explore the immediate analgesic effects and underlying cortical mechanisms of repetitive peripheral magnetic stimulation (rPMS), a non-invasive physiotherapy technique, in patients with NNP and NLBP. Methods A total of 181 patients (75 NNP, 106 NLBP) were randomized to receive either a single session of active or sham rPMS (10 Hz, 100% RMT, 1200 pulses) targeted at the most painful neck or lower back area. The primary outcome measured was the change in pain intensity on the numerical rating scale (NRS), while secondary outcomes included the pressure pain threshold (PPT). Cortical hemodynamic activity was assessed using fNIRS over the dorsolateral prefrontal cortex (DLPFC) and other pre-defined pain-processing regions. Results Active rPMS resulted in significantly greater analgesia compared to sham stimulation, as indicated by a notable decrease in NRS scores and an increase in PPT (both P  < 0.001). fNIRS revealed differential neuromodulatory effects: active rPMS significantly reduced pain-evoked activation in the left DLPFC (L-DLPFC) in NNP patients and bilaterally in NLBP patients. Pooled analysis revealed robust bilateral prefrontal inhibition (L-DLPFC, P  = 0.003; R-DLPFC, P  = 0.033). There was a significant pre-to-post reduction in DLPFC activation only in the active rPMS group. Interestingly, in the NNP group, ΔNRS were correlated with ΔL-DLPFC ( r  = 0.313, P  = 0.006), and the NLBP group showed bilateral correlations, with ΔNRS associated with both ΔL-DLPFC ( r  = 0.226, P  = 0.020) and ΔR-DLPFC ( r  = 0.298, P  = 0.002). Furthermore, the pooled analysis of all subjects demonstrated a significant bilateral relationship between ΔNRS and ΔDLPFC (ΔL-DLPFC: r  = 0.257, P  < 0.001; ΔR-DLPFC: r  = 0.244, P  = 0.001). Conclusion A single session of rPMS offers rapid and effective analgesia for both NNP and NLBP by modulating DLPFC activity. Our findings underscore a central neuromodulatory mechanism and suggest that the DLPFC may serve as a promising target for non-invasive brain stimulation therapies in the management of NNP and NLBP. Trial registration The Ethics Review Committee of the Xijing Hospital Affiliated to Air Force Medical University, No. KY-20222009-F-1; www.chictr.org.cn , ChiCTR2200060844, Date of Registration: 12 June 2022.

Back pain is a major health issue in Western countries and 60%–80% of adults are likely to experience low back pain. This paper explores the impact of back pain on society and the role of physical activity for treatment of non-specific low back pain. A review of the literature was carried out using the databases SPORTDiscuss, Medline and Google Scholar. A general exercise programme that combines muscular strength, flexibility and aerobic fitness is beneficial for rehabilitation of non-specific chronic low back pain. Increasing core muscular strength can assist in supporting the lumbar spine. Improving the flexibility of the muscle-tendons and ligaments in the back increases the range of motion and assists with the patient’s functional movement. Aerobic exercise increases the blood flow and nutrients to the soft tissues in the back, improving the healing process and reducing stiffness that can result in back pain.