Polyfluoroalkyl Tag Decoration Enables Significantly Enhanced Tumor Penetration Ability of a PTK7 Targeting Aptamer.

Aptamers are widely used molecular recognition tools in targeted therapy, but their ability to effectively penetrate deep into solid tumors remains a significant challenge, leading to suboptimal treatment efficacy. Here, we developed a polyfluoroalkyl (PFA) decoration strategy to enhance aptamer recognition, cell internalization, and solid tumor penetration. Our results indicate that PFA with around 11 fluorine atoms significantly improves aptamer internalization both in vitro and in vivo settings. However, we also observed that the use of PFA tags containing 19 and 23 fluorine atoms on aptamers resulted in nonspecific cell anchoring in control cell lines, affecting the specificity of aptamers. Overall, we found that using a chemical modification strategy could enhance the deep tumor penetration ability of aptamers and validate their effectiveness in vivo. This approach has significant practical applications in targeted drug delivery for cancer treatment.

Combined biomass network design: A new integrated approach based on ArcGIS.

In light of contemporary energy and environmental objectives, a pivotal transformation of the energy system, encompassing biomass energy, is imperative. A notable challenge in biomass energy facility layout planning is the trade-off between high-efficiency production and the associated investment costs. To harmonize energy efficiency with economy viability, a hybrid layout with the simultaneous construction of centralized and decentralized biomass energy facilities has emerged as a crucial strategic solution. However, the delineation methods for these two layouts lack explicit data support. This study established a population density threshold (PDT) suitable for selecting the distributed layout and employed population density as the criterion for delineating the two layouts. Taking Fuxin City as an example, hybrid layout planning schemes were generated under different PDTs, and a cost and energy benefit analysis framework was developed for these schemes. The results indicated that the scheme with a PDT of 145 person/km2 exhibited the highest energy and economic comprehensive benefits. Compared to a single layout, the planning strategy proposed in this study could achieve nearly the same energy surplus level while saving an investment cost ranging from 2403.9 million CNY to 25,000.23 million CNY. The findings are applicable to other regions with similar conditions, and the analysis framework proposed in this study can be utilized in formulating biomass development strategies for other countries and regions.

Role of Exercise on Inflammation Cytokines of Neuropathic Pain in Animal Models.

Neuropathic pain (NP) resulting from a lesion or disease of the somatosensory system can lead to loss of function and reduced life quality. Neuroinflammation plays a vital role in the development and maintenance of NP. Exercise as an economical, effective, and nonpharmacological treatment, recommended by clinical practice guidelines, has been proven to alleviate chronic NP. Previous studies have shown that exercise decreases NP by modifying inflammation; however, the exact mechanisms of exercise-mediated NP are unclear. Therefore, from the perspective of neuroinflammation, this review mainly discussed the effects of exercise on inflammatory cytokines in different parts of NP conduction pathways, such as the brain, spinal cord, dorsal root ganglion, sciatic nerve, and blood in rat/mice models. Results suggested that exercise training could modulate neuroinflammation, inhibit astrocyte glial cell proliferation and microglial activation, alter the macrophage phenotype, reduce the expression of proinflammatory cytokines, increase anti-inflammatory cytokine levels, and positively modulate the state of the immune system, thereby relieving NP.

Associations between Physical Activity and the Incidence of Cerebrovascular Disease or All-Cause Mortality among 146,742 Older Adults: A 13-Year Prospective Cohort Study.

OBJECTIVES: Although studies have indicated that physical activity (PA) is related to cardiovascular disease, the specific association between PA and incident cerebrovascular disease (CBVD) remains uncertain. The current study aimed to investigate the associations between PA levels and the CBVD incidence or all-cause mortality. DESIGN: Prospective cohort study. SETTINGS AND PARTICIPANTS: Older participants (aged >60 years) from the UK Biobank. METHODS: The baseline PA was classified as total, light, moderate, and vigorous PA based on the metabolic equivalent-minutes per week (MET-min/wk) and considered as exposures, whereas CBVD incidence and all-cause mortality were considered as the outcomes. Cox proportional hazards were used to calculate the hazard ratios (HRs) and 95% CIs for the influence of the association between PA and CBVD incidence and all-cause mortality. RESULTS: A total of 146,742 participants aged 60 years and older were included. During a median follow-up period of 13.5 years (interquartile range of 12.8-14.2), 9338 older individuals developed CBVD and 3033 death were recorded (including 767 CBVD-related deaths). High volumes of PA were consistently associated with lower risks of CBVD and all-cause mortality. The lowest risk of CBVD incidence was observed at 2001-2500 MET-min/wk of total PA (HR 0.61, 95% CI 0.53-0.70), and the lowest risk of all-cause mortality was observed at 2501-5000 MET-min/wk (HR 0.52, 95% CI 0.43-0.63) in older adults. Total PA at 2001-2500 MET-min/wk significantly reduced the CBVD incidence in older women (HR 0.57, 95% CI 0.46-0.71), which was more pronounced than that in older men (HR for 2001-2500 MET-min/wk: 0.64, 95% CI 0.50-0.77). CONCLUSIONS AND IMPLICATIONS: Total PA at 2001-2500 MET-min/wk significantly reduced the risk of incident CBVD and all-cause mortality in adults aged >60 years, although the extents of risk reduction vary in men and women.

Cobalt-Catalyzed Selective Hydroboration of 1,3-Enynes with HBpin toward 1,3-Dienylboronate Esters.

An efficient cobalt-catalyzed selective hydroboration of 1,3-enynes with HBpin toward 1,3-dienylboronate esters is disclosed. With a commercially available catalytic system of Co(acac)2 and dppf, the hydroboration reactions proceeded well to afford a wide range of 1,3-dienylborates in moderate to high yields. This protocol features a cheap base-metal catalytic system, broad substrate scope, excellent selectivity, easy gram-scale preparation, and good functional group tolerance and provides access to synthetically valuable 1,3-dienylborates.

Associations between back pain incidence, and physical activity and sedentary behaviours: A prospective cohort study with data from over 365,000 participants.

OBJECTIVE: To examine the associations between (i) various types of physical activity and the risk of back pain incidence, and (ii) the influence of substituting sedentary behaviours with physical activities on back pain incidence. DESIGN: A prospective cohort study. METHODS: We analyzed UK Biobank data collected from 365,307 participants who were free of back pain at baseline. The exposures were total, light, moderate and vigorous physical activity, and sedentary behaviours. The outcome was back pain incidence. The main statistical models were the Cox proportional hazard model and the isotemporal substitution model. RESULTS: In the follow-up time (median, 12.97 years; inter-quartile range, 12.10-13.71), 25,189 individuals developed back pain. The associations between all types of physical activity and incident back pain were significantly non-linear (p < 0.001) among the general population and other subgroups. High physical activity was associated with a decreased risk of back pain compared with no physical activity. The lowest risk occurred in the 1801-2400 MET-min/week subgroup of total physical activity (HR 0.64, 95% CI 0.59-0.69), approximately consisting of 1200, 600, and 600 MET-min/week of light, moderate and vigorous physical activity, respectively. Extremely high vigorous physical activity was related to high risk, specifically in males (HR 1.13, 95% CI 1.02-1.25). Replacing 1 hour/day of sedentary behaviours with an equal time of physical activity reduced the risk of incident back pain by 2%-8% (p < 0.05). CONCLUSION: Physical activity was related to a reduced risk of back pain incidence (except over-high vigorous physical activity). Substituting sedentary behaviours with physical activities reduced the risk of future back pain.

Ni-Catalyzed Csp2 and Csp3 Coupling for Divergent Bisboronic Ester Synthesis.

Bisboronic esters are critical compounds in various research fields, including drug discovery, chemical biology, and material sciences. Currently, the bisboronic esters with reactive functional groups are difficult to synthesize; this is partially due to the lack of a robust method to produce these products with diverse structures and various functional groups at specific locations. To overcome this issue, this study introduced a Ni-catalysis approach to produce bisboronic esters efficiently via cross-coupling and homocoupling using readily available halogenated boronic esters as the starting material under mild reaction conditions. This newly developed strategy enables Csp2-Csp2, Csp3-Csp3, and Csp2-Csp3 couplings, demonstrating a broad substrate scope and excellent compatibility with various functional groups.

The Discharge Behavior and Mechanism of Polyimide Aerogel under Electron Irradiation.

The response and mechanism of polyimide aerogel under electron irradiations were investigated. The experimental results indicated that electron irradiation could not damage the skeleton polyimide in the aerogel due to its high stability, but could result in a discharge within. The morphology of the discharge shows some dendritic discharge patterns, and the material surrounding the discharge channels was carbonized. The numerical simulation results indicated that the incident electrons, and also large amount induced secondary electrons, would be deposited inhomogeneously within the nano-porous polyimide aerogel. This would result in forming an ultra-high electrical potential of up to about 8.5 × 1010 V/m (which is far higher than the breakdown strength (2 × 108 V/m) of bulk polyimide materials) in a local region. This may be the leading cause of the obvious discharge in the materials. Furthermore, it was found that the actual reason for the discharge is related to the residual gas within the nano-porous structure; namely, the more internal residual gas (as a shorter-time vacuum pumping in the irradiated chamber), the more serious the discharge phenomenon. Correspondingly, the phenomenon may largely consist of both residual-gas discharge and surface flashover due to ultra-high local potentials induced by unevenly deposited charges in the porous aerogel.

Demographic and clinical characteristics associated with failure of physical therapy in chronic low back pain: a secondary analysis from a randomized controlled trial.

BACKGROUND: The effect of physical therapy on pain and disability alleviation in patients with chronic low back pain (cLBP) has been demonstrated, but the risk factors for treatment failure remain unknown. AIM: To explore the associations of baseline demographic and clinical characteristics with treatment failure after physical therapy intervention for cLBP. DESIGN: A secondary analysis of a single-blind randomized clinical trial. SETTING: A rehabilitation hospital. POPULATION: A total of 98 patients with cLBP completed the 12-month measurement. METHODS: Patients were randomly grouped into 3-month therapeutic aquatic exercise or physical therapy modalities. The primary outcome was treatment failure, which was defined as a decrease in the numeric rating scale to less than 2.0 points at 12-month follow-up. Associations between baseline demographic and clinical characteristics with risk of treatment failure were assessed by logistic regressions. RESULTS: The pain intensity in the failure cases was alleviated after 3-month intervention but continuously increased at 6- and 12-month follow-up (P<0.05). Old age was significantly associated with an increased risk of treatment failure (adjusted OR 3.26, 95% CI 1.11-9.60). Compared with those receiving physical therapy modalities, the patients receiving therapeutic aquatic exercise had less risk of treatment failure (adjusted OR 0.19, 95% CI 0.08-0.47), and age (P=0.022) was a modifier for this association. CONCLUSIONS: Compared with younger ones, older patients with cLBP had a higher risk of treatment failure after physical therapy and gained a stronger benefit of long-term pain alleviation from therapeutic aquatic exercise. CLINICAL REHABILITATION IMPACT: Therapeutic aquatic exercise is an effective therapy for cLBP and more helpful for preventing treatment failure than physical therapy modalities, especially for older patients.

Genome-Wide Analysis of the TCP Transcription Factor Gene Family in Pepper (Capsicum annuum L.).

TCP transcription factors play a key role in regulating various developmental processes, particularly in shoot branching, flower development, and leaf development, and these factors are exclusively found in plants. However, comprehensive studies investigating TCP transcription factors in pepper (Capsicum annuum L.) are lacking. In this study, we identified 27 CaTCP members in the pepper genome, which were classified into Class I and Class II through phylogenetic analysis. The motif analysis revealed that CaTCPs in the same class exhibit similar numbers and distributions of motifs. We predicted that 37 previously reported miRNAs target 19 CaTCPs. The expression levels of CaTCPs varied in various tissues and growth stages. Specifically, CaTCP16, a member of Class II (CIN), exhibited significantly high expression in flowers. Class I CaTCPs exhibited high expression levels in leaves, while Class II CaTCPs showed high expression in lateral branches, especially in the CYC/TB1 subclass. The expression profile suggests that CaTCPs play specific roles in the developmental processes of pepper. We provide a theoretical basis that will assist in further functional validation of the CaTCPs.

Physical therapy for acute and sub-acute low back pain: A systematic review and expert consensus.

OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.

Mechanisms of transcranial direct current stimulation (tDCS) for pain in patients with fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is a recurrent pain condition that can be challenging to treat. Transcranial direct current stimulation (tDCS) has become a promising non-invasive therapeutic option in alleviating FMS pain, but the mechanisms underlying its effectiveness are not yet fully understood. In this article, we discuss the most current research investigating the analgesic effects of tDCS on FMS and discuss the potential mechanisms. TDCS may exert its analgesic effects by influencing neuronal activity in the brain, altering cortical excitability, changing regional cerebral blood flow, modulating neurotransmission and neuroinflammation, and inducing neuroplasticity. Overall, evidence points to tDCS as a potentially safe and efficient pain relief choice for FMS by multiple underlying mechanisms. This article provides a thorough overview of our ongoing knowledge regarding the mechanisms underlying tDCS and emphasizes the possibility of further studies to improve the clinical utility of tDCS as a pain management tool.

Reliability and Validity of the Star Excursion Balance Test for Evaluating Dynamic Balance of Upper Extremities.

BACKGROUND: Upper extremity (UE) dynamic balance is a significant physical fitness ability, which includes high-level neuromuscular proprioception, joint mobility, force, and coordination. The evaluation methods of UE dynamic balance are insufficient and lack experimental support. The Star Excursion Balance Test (SEBT) is a reliable assessment of dynamic balance and injury risk of the lower extremity. HYPOTHESIS: The UE-SEBT is a reliable and reproducible approach for evaluating dynamic balance of UEs. STUDY DESIGN: Observational study. LEVEL OF EVIDENCE: Level 4. METHODS: This cross-sectional study recruited 65 healthy adults. All participants were required to complete UE-SEBT, UE Y-balance test (UE-YBT), maximal voluntary isometric contraction (MVIC) of UE, closed kinetic chain UE stability test (CKCUEST), trunk flexor endurance test (TFET), trunk extensor endurance test (TEET), and lateral trunk endurance test (LTET). Intra- and inter-rater reliability and the correlation of UE-SEBT with other outcomes were measured. RESULTS: Among the participants, the intra- and interoperator reliability of UE-SEBT in all directions and composite score achieved a moderate-to-excellent (intraclass correlation coefficients [ICC], 0.729-0.946) reliability. For validity, the UE-SEBT had a moderate to very strong correlation with UE-YBT (r = 0.315-0.755, P < 0.01) and a strong correlation with CKCUEST (r = 0.4-0.67, P < 0.01). Furthermore, the UE-SEBT performance showed weak-to-strong correlations with MVIC (r = 0.26-0.43, P < 0.05). UE-SEBT was also correlated with LTET, TEET, and TFET to varying degrees. CONCLUSION: UE-SEBT has good reliability and validity to assess UE dynamic balance compared with other tests. CLINICAL RELEVANCE: UE-SEBT can be used as a clinical assessment method to evaluate UE dynamic balance and injury prevention.

High Contrast Bioimaging of Tumor and Inflammation with a Bicyclic Dioxetane Chemiluminescent Probe.

The link between inflammation and the evolution of cancer is well established. Visualizing and tracking both tumor proliferation and the associated inflammatory response within a living organism are vital for dissecting the nexus between these two processes and for crafting precise treatment modalities. We report the creation and synthesis of an advanced NIR chemiluminescence probe that stands out for its exceptional selectivity, extraordinary sensitivity at nanomolar concentrations, swift detection capabilities, and broad application prospects. Crucially, this probe has been successfully utilized to image endogenous ONOO- across different inflammation models, including abdominal inflammation triggered by LPS, subcutaneous inflammatory conditions, and tumors grafted onto mice. These findings highlight the significant promise of chemiluminescence imaging in enhancing our grasp of the intricate interplay between cancer and inflammation and in steering the development of potent, targeted therapeutic strategies.

OsNAC5 orchestrates OsABI5 to fine-tune cold tolerance in rice.

Due to its tropical origins, rice (Oryza sativa) is susceptible to cold stress, which poses severe threats to production. OsNAC5, a NAC-type transcription factor, participates in the cold stress response of rice, but the detailed mechanisms remain poorly understood. Here, we demonstrate that OsNAC5 positively regulates cold tolerance at germination and in seedlings by directly activating the expression of ABSCISIC ACID INSENSITIVE 5 (OsABI5). Haplotype analysis indicated that single nucleotide polymorphisms in a NAC-binding site in the OsABI5 promoter are strongly associated with cold tolerance. OsNAC5 also enhanced OsABI5 stability, thus regulating the expression of cold-responsive (COR) genes, enabling fine-tuned control of OsABI5 action for rapid, precise plant responses to cold stress. DNA affinity purification sequencing coupled with transcriptome deep sequencing identified several OsABI5 target genes involved in COR expression, including DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR 1A (OsDREB1A), OsMYB20, and PEROXIDASE 70 (OsPRX70). In vivo and in vitro analyses suggested that OsABI5 positively regulates COR gene transcription, with marked COR upregulation in OsNAC5-overexpressing lines and downregulation in osnac5 and/or osabi5 knockout mutants. This study extends our understanding of cold tolerance regulation via OsNAC5 through the OsABI5-CORs transcription module, which may be used to ameliorate cold tolerance in rice via advanced breeding.

Association of persistent musculoskeletal pain with dementia risk score in adults aged 45 years or older: The China health and retirement longitudinal study.

BACKGROUND: Recent studies have confirmed an association between pain and dementia. Whether musculoskeletal pain in the spine, upper limbs, and lower limbs is associated with dementia risk remains unclear. The longitudinal effect of musculoskeletal pain on dementia risk also remains unclear. AIMS: This work aimed to investigate the association between musculoskeletal pain and dementia risk score. METHODS: We conducted cross-sectional and longitudinal analyses using data from the China Health and Retirement Longitudinal Study. Participants aged 45 years or older were recruited in 2011. A total of 10,759 participants with complete pain information at baseline were eligible for the cross-sectional analysis, and 5,855 were eligible for the longitudinal analyses. We utilized the Rotterdam Study Basic Dementia Risk Model (BDRM) to assess dementia risk. Generalized estimating equations were used to investigate the associations. RESULTS: Compared with participants without persistent musculoskeletal pain, those with persistent musculoskeletal pain (standardized, ß = 0.83; 95 % CI: 0.06, 1.61, p = 0.036), multisite pain (sites≧5; ß = 1.52; 95 % CI: 0.13, 2.91, p = 0.032), neck pain (ß = 2.33; 95 % CI: 0.41, 4.25, p = 0.018), back pain (ß = 2.12; 95 % CI: 0.43, 3.82, p = 0.014), waist pain (ß = 1.09; 95 % CI: 0.07, 2.11, p = 0.037), shoulder pain (ß = 1.74; 95 % CI: 0.46, 3.02, p = 0.008), wrist pain (ß = 2.72; 95 % CI: 0.42, 5.02, p = 0.021), and knee pain (ß = 1.91; 95 % CI: 0.70, 3.13, p = 0.002) had a higher BDRM score during 4 years of follow-up. CONCLUSIONS: Promoting the management of musculoskeletal pain may be beneficial in reducing the dementia risk score.

Identification and expression analysis of LEA gene family members in pepper (Capsicum annuum L.).

Pepper (Capsicum annuum L.) is an economically important crop containing capsaicinoids in the seed and placenta, which has various culinary, medical, and industrial applications. Late embryogenesis abundant (LEA) proteins are a large group of hydrophilic proteins participating in the plant stress response and seed development. However, to date there have been no genome-wide analyses of the LEA gene family in pepper. In the present study, 82 LEA genes were identified in the C. annuum genome and classified into nine subfamilies. Most CaLEA genes contain few introns (≤ 2) and are unevenly distributed across 10 chromosomes. Eight pairs of tandem duplication genes and two pairs of segmental duplication genes were identified in the LEA gene family; these duplicated genes were highly conserved and may have performed similar functions during evolution. Expression profile analysis indicated that CaLEA genes exhibited different tissue expression patterns, especially during embryonic development and stress response, particularly in cold stress. Three out of five CaLEA genes showed induced expression upon cold treatment. In summary, we have comprehensively reviewed the LEA gene family in pepper, offering a new perspective on the evolution of this family.

Association between smoking and incident back pain: A prospective cohort study with 438 510 participants.

Background: Although smoking is a known potential contributor to back pain, there is still a lack of quantitative studies on the effects of different doses on back pain (BP) occurrence, including a lack of a longitudinal cohorts. To address this gap, we aimed to investigate the association between various smoking-related exposures and back pain incidence to advance global efforts toward smoking cessation and guide primary prevention of BP. Methods: In this prospective cohort study, we retrieved data on 438 510 patients from the UK Biobank who were free of back pain and who were recruited in 2006-2010, and followed them up from baseline through 1 April 2022. We extracted data on smoking-related exposures, including smoking status (SS), number of cigarettes smoked daily (CPD), and pack-years of own smoking (PY) and examined back pain incidence as an outcome. We used a Cox proportional hazard model adjusted for several covariates, multiple imputation methods, and population attribution fraction. Results: During the median follow-up of 12.98 years, 31 467 participants developed BP, with incidence rates in former and current smokers of 1.13 (95% confidence interval (CI) = 1.10-1.16, P < 0.000) and 1.50 (95% CI = 1.45-1.56, P < 0.000), respectively. The hazard ratios (HRs) of participants who smoked more than 30 CPD and those with more than 30 PY were 1.45 (95% CI = 1.36-1.55, P < 0.000) and 1.45 (95% CI = 1.40-1.50, P < 0.000), respectively. Relative to male, female smokers were at more risk of developing BP. Not smoking, quitting smoking, and reducing CPD and PY could lower the BP risk by 7.8%, 5.4%, 9.8%, and 18.0%, respectively. Conclusions: Ever smoking, higher cigarette consumption daily, and increased smoking intensity were associated with an increased BP risk. This association was stronger in female smokers. Not smoking, smoking cessation, and reducing smoking volume and intensity were effective measures to prevent BP occurrence.

Comparative Study of Hydroxytyrosol Acetate and Hydroxytyrosol in Activating Phase II Enzymes.

Nuclear factor E2-related factor 2 (Nrf2) is fundamental to the maintenance of redox homeostasis within cells via the regulation of a series of phase II antioxidant enzymes. The unique olive-derived phenolic compound hydroxytyrosol (HT) is recognized as an Nrf2 activator, but knowledge of the HT derivative hydroxytyrosol acetate (HTac) on Nrf2 activation remains limited. In this study, we observed that an HT pretreatment could protect the cell viability, mitochondrial membrane potential, and redox homeostasis of ARPE-19 cells against a t-butyl hydroperoxide challenge at 50 µM. HTac exhibited similar benefits at 10 µM, indicating a more effective antioxidative capacity compared with HT. HTac consistently and more efficiently activated the expression of Nrf2-regulated phase II enzymes than HT. PI3K/Akt was the key pathway accounting for the beneficial effects of HTac in ARPE-19 cells. A further RNA-Seq analysis revealed that in addition to the consistent upregulation of phase II enzymes, the cells presented distinct expression profiles after HTac and HT treatments. This indicated that HTac could trigger a diverse cellular response despite its similar molecular structure to HT. The evidence in this study suggests that Nrf2 activation is the major cellular activity shared by HTac and HT, and HTac is more efficient at activating the Nrf2 system. This supports its potential future employment in various disease management strategies.