Prevalence and risk factors of occupational neck pain in Chinese male fighter pilots: a cross-sectional study based on questionnaire and cervical sagittal alignment.

Background: Neck pain (NP) is a common musculoskeletal disorder among fighter pilots and has become a rising concern due to its detrimental impact on military combat effectiveness. The occurrence of NP is influenced by a variety of factors, but less attention has been paid to the association of NP with demographic, occupational, and cervical sagittal characteristics in this group. This study aimed to investigate the prevalence and risk factors of NP in Chinese male fighter pilots using a questionnaire and cervical sagittal measurements. Methods: Demographic and flight-related data, as well as musculoskeletal pain information, were gathered from Chinese male fighter pilots via a self-report questionnaire. Cervical sagittal parameters were measured and subtypes were classified using standardized lateral cervical radiographs. Differences in various factors between the case and control groups were analyzed using t-tests or chi-square tests. Binary logistic regressions were conducted to explore potential risk factors contributing to NP. Predictors were presented as crude odds ratios (CORs) and adjusted odds ratios (AORs), along with their respective 95% confidence intervals (CIs). Results: A total of 185 male fighter pilots were included in this cross-sectional study. Among them, 96 (51.9%) reported experiencing NP within the previous 12 months. The multivariate regression analysis revealed that continuous flight training (AOR: 4.695, 95% CI: 2.226-9.901, p < 0.001), shoulder pain (AOR: 11.891, 95% CI: 4.671-30.268, p < 0.001), and low back pain (AOR: 3.452, 95% CI: 1.600-7.446, p = 0.002) were significantly associated with NP. Conclusion: The high 12-month prevalence of NP among Chinese male fighter pilots confirms the existence of this growing problem. Continuous flight training, shoulder pain, and low back pain have significant negative effects on pilots' neck health. Effective strategies are necessary to establish appropriate training schedules to reduce NP, and a more holistic perspective on musculoskeletal protection is needed. Given that spinal integrated balance and compensatory mechanisms may maintain individuals in a subclinical state, predicting the incidence of NP in fighter pilots based solely on sagittal characteristics in the cervical region may be inadequate.

Metabolomics-based analysis of flavonoid metabolites in Chinese jujube and sour jujube fruits from different harvest periods.

Chinese jujube (Ziziphus jujuba Mill.) and sour jujube (Ziziphus spinosa Hu.) fruits have health benefits because they contain bioactive compounds such as flavonoids. However, differences in the flavonoid metabolites of these two fruits remain unclear. We determined the flavonoids present in Z. jujuba cv. Hupingzao (HPZ) and Z. spinosa cv. Taigusuanzao (TGSZ) from two different harvest periods fruits: HPZ white period (HW) and HPZ red period (HR) as well as TGSZ white period (SW) and TGSZ red period (SR). We identified 123 flavonoid metabolites: 40 flavonols, 37 flavones, 12 anthocyanins, 9 dihydroflavones, 8 flavanols, 7 flavonoid carbonosides, 5 dihydroflavonols, 3 isoflavones, and 2 chalcones. The total flavonoid content of both HPZ and TGSZ decreased with fruit development and was significantly higher in TGSZ than in HPZ fruits. Moreover, we detected 63, 81, 56, and 63 differential flavonoid metabolites (DFMs) between HW and HR (two upregulated and 61 downregulated), SW and SR (four upregulated and 77 downregulated), HW and SW (54 upregulated and two downregulated), and HR and SR (62 upregulated and one downregulated), respectively. KEGG pathway annotation and enrichment analysis showed that 22 DFMs were annotated seven relevant metabolic pathways, among which flavonoid biosynthesis pathway and secondary metabolites biosynthesis pathway were the main pathways, and flavanols were the primary metabolites that influenced the difference in flavonoid accumulation between the fruits. To our knowledge, this is the first study to reveal the differences in flavonoid metabolism between Chinese jujube and sour jujube. Our findings may facilitate the comprehensive use of functional flavonoids. PRACTICAL APPLICATION: Chinese jujube (Ziziphus jujuba Mill.) and sour jujube (Ziziphus spinosa Hu.) fruits have health benefits because they contain bioactive compounds such as flavonoids. However, differences in the flavonoid metabolites of these two fruits remain unclear. We determined the flavonoids present in Z. jujuba cv. Hupingzao (HPZ) and Z. spinosa cv. Taigusuanzao (TGSZ) from two different harvest periods. Our findings may facilitate the comprehensive use and product research of functional flavonoids of jujube.

Composition and content of phenolic acids and flavonoids among the different varieties, development stages, and tissues of Chinese Jujube (Ziziphus jujuba Mill.).

The composition and content of phenolic acids and flavonoids among the different varieties, development stages, and tissues of Chinese jujube (Ziziphus jujuba Mill.) were systematically examined using ultra-high-performance liquid chromatography to provide a reference for the evaluation and selection of high-value resources. Five key results were identified: (1) Overall, 13 different phenolic acids and flavonoids were detected from among the 20 excellent jujube varieties tested, of which 12 were from the fruits, 11 from the leaves, and 10 from the stems. Seven phenolic acids and flavonoids, including (+)-catechin, rutin, quercetin, luteolin, spinosin, gallic acid, and chlorogenic acid, were detected in all tissues. (2) The total and individual phenolic acids and flavonoids contents significantly decreased during fruit development in Ziziphus jujuba cv.Hupingzao. (3) The total phenolic acids and flavonoids content was the highest in the leaves of Ziziphus jujuba cv.Hupingzao, followed by the stems and fruits with significant differences among the content of these tissues. The main composition of the tissues also differed, with quercetin and rutin present in the leaves; (+)-catechin and rutin in the stems; and (+)-catechin, epicatechin, and rutin in the fruits. (4) The total content of phenolic acid and flavonoid ranged from 359.38 to 1041.33 µg/g FW across all examined varieties, with Ziziphus jujuba cv.Jishanbanzao having the highest content, and (+)-catechin as the main composition in all 20 varieties, followed by epicatechin, rutin, and quercetin. (5) Principal component analysis showed that (+)-catechin, epicatechin, gallic acid, and rutin contributed to the first two principal components for each variety. Together, these findings will assist with varietal selection when developing phenolic acids and f lavonoids functional products.

Changes of bioactive components and antioxidant potential during fruit development of Prunus humilis Bunge.

Dynamic changes in flavonoid, total phenol, and antioxidant potential in different Prunus humilis accessions during fruit development stages were studied in order to provide a reference for the optimum harvest time for flavonoid extraction. 'Nongda 4', 'Nongda 5', 'DS-1' and '02-16' were selected as plant materials to determine the content of flavonoid, total phenol and antioxidant indices during six fruit development stages. Changes in total flavonoid content (TFC) and total phenol content (TPC) in different accessions of P. humilis were slightly different depending on the development stage of P. humilis fruit. TFC and TPC in 'Nongda 5' fruit showed a trend of continuous decline. There was a small increase in TFC and TPC from the young fruit stage to the stone hardening stage, followed by a decreasing trend, and then to the lowest level at the ripening stage of 'Nongda 4', 'DS-1', and '02-16' fruits. The trend of antioxidant capacity (ABTS, FRAP, DPPH) with the TFC and TPC of P. humilis fruit was basically the same, and the correlation analysis results showed that the TFC of P. humilis fruit was positively correlated with the antioxidant indices (P<0.01). Catechin (CC), rutin (RT), and quercetin-7-O-ß-D-glucopyranoside (Q7G) were detected in all the fruit development stages of the four P. humilis fruits. Among them, catechin was the most abundant component, accounting for approximately 10%. Myricetin (MC) and quercetin (QC) were generally detected only in the early fruit development stage, but not in the later fruit development stage. Correlation analysis showed that the flavonoid components with TFC, TPC, and antioxidant indices differed between the different accessions. RT, CC, and liquiritigenin (LR) had a stronger correlation with TFC and antioxidant indices. Cyanidin-3-O-glucoside (C3G) was not detected until the coloring stage in two red P. humilis accessions ('Nongda 4' and 'DS-1'), and so it is better to choose a red P. humilis fruit to extract C3G at the ripening stage. Selecting an early stage of fruit development, especially the stone hardening stage, was important for extracting flavonoids, total phenols and other components. We believe that our results will provide basic information and reference for evaluation of fruit nutrition and health benefits, breeding of functional new varieties, and efficient utilization of P. humilis fruit.

Co-delivery of TRAIL and siHSP70 using hierarchically modular assembly formulations achieves enhanced TRAIL-resistant cancer therapy.

The combined therapy of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and heat shock protein 70-targeting siRNA (siHSP70) has shown an improved anti-tumor effect on TRAIL-resistant tumor. However, vehicles to co-deliver these two biopharmaceuticals are challenging because of the distinct location of their targets on the cell surface and in the cytosol. Here we developed a hierarchically modular assembly formulation (TH-s-RSC) via the copper-free click reaction to co-encapsulate the positively-charged TRAIL and negatively-charged siHSP70 and release them in the extracellular space and cytoplasm. We demonstrate that TH-s-RSC can protect the packaged biopharmaceuticals through its hyaluronic acid shell in vivo, and sequentially release TRAIL in response to extracellular molecular including hyaluronidase (HAase) and matrix metalloproteinase 2 (MMP2), followed by the release of siHSP70 triggered by the reductive conditions in the cytoplasm. We showed that the complementary activity of TRAIL and siHSP70 exhibited superior synergistic anticancer efficacy in both A549 lung cancer xenograft models and 4T1 lung metastatic breast cancer models, compared to either treatment alone. Our strategy provides a promising platform for safe and effective co-delivery and dual-site targeting of biopharmaceuticals in cancer treatment that may be applicable in the future.

Experimental demonstration of in-plane negative-angle refraction with an array of silicon nanoposts.

Controlling an optical beam is fundamental in optics. Recently, unique manipulation of optical wavefronts has been successfully demonstrated by metasurfaces. However, these artificially engineered nanostructures have thus far been limited to operate on light beams propagating out-of-plane. The in-plane operation is critical for on-chip photonic applications. Here, we demonstrate an anomalous negative-angle refraction of a light beam propagating along the plane, by designing a thin dielectric array of silicon nanoposts. The circularly polarized dipoles induced by the high-permittivity nanoposts at the scattering resonance significantly shape the wavefront of the light beam and bend it anomalously. The unique capability of a thin line of the nanoposts for manipulating in-plane wavefronts makes the device extremely compact. The low loss all-dielectric structure is compatible with complementary metal-oxide semiconductor technologies, offering an effective solution for in-plane beam steering and routing for on-chip photonics.

The NHLBI-sponsored Consortium for preclinicAl assESsment of cARdioprotective therapies (CAESAR): a new paradigm for rigorous, accurate, and reproducible evaluation of putative infarct-sparing interventions in mice, rabbits, and pigs.

RATIONALE: Despite 4 decades of intense effort and substantial financial investment, the cardioprotection field has failed to deliver a single drug that effectively reduces myocardial infarct size in patients. A major reason is insufficient rigor and reproducibility in preclinical studies. OBJECTIVE: To develop a multicenter, randomized, controlled, clinical trial-like infrastructure to conduct rigorous and reproducible preclinical evaluation of cardioprotective therapies. METHODS AND RESULTS: With support from the National Heart, Lung, and Blood Institute, we established the Consortium for preclinicAl assESsment of cARdioprotective therapies (CAESAR), based on the principles of randomization, investigator blinding, a priori sample size determination and exclusion criteria, appropriate statistical analyses, and assessment of reproducibility. To validate CAESAR, we tested the ability of ischemic preconditioning to reduce infarct size in 3 species (at 2 sites/species): mice (n=22-25 per group), rabbits (n=11-12 per group), and pigs (n=13 per group). During this validation phase, (1) we established protocols that gave similar results between centers and confirmed that ischemic preconditioning significantly reduced infarct size in all species and (2) we successfully established a multicenter structure to support CAESAR's operations, including 2 surgical centers for each species, a Pathology Core (to assess infarct size), a Biomarker Core (to measure plasma cardiac troponin levels), and a Data Coordinating Center-all with the oversight of an external Protocol Review and Monitoring Committee. CONCLUSIONS: CAESAR is operational, generates reproducible results, can detect cardioprotection, and provides a mechanism for assessing potential infarct-sparing therapies with a level of rigor analogous to multicenter, randomized, controlled clinical trials. This is a revolutionary new approach to cardioprotection. Importantly, we provide state-of-the-art, detailed protocols ("CAESAR protocols") for measuring infarct size in mice, rabbits, and pigs in a manner that is rigorous, accurate, and reproducible.