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Hematopoiesis originates in the yolk sac, which forms prior to the establishment of blood circulation and exhibits distinct developmental processes between primates and mice. Despite increasing appreciation of yolk sac hematopoiesis for its lifelong contribution to the adult hematopoietic system and its regulatory roles in organogenesis, cross-species differences, particularly before the onset of blood circulation, remain incompletely understood. In this study, we constructed an integrative cross-species transcriptome atlas of pre-circulation hematopoiesis in humans, monkeys ( Macaca fascicularis ), and mice. This analysis identified conserved populations between primates and mice, while also revealing more differentiated myeloid, erythroid, and megakaryocytic lineages in pre-circulation primates compared to mice. Specifically, SPP1 -expressing macrophages were detected in primates before the onset of blood circulation but were absent in mice. Cell-cell communication analysis identified CSF1 + extraembryonic mesoderm cells as a potential supportive niche for macrophage generation, with ligand-receptor interactions between macrophages and other cell populations in the human yolk sac. Interestingly, pre-circulation SPP1 + macrophages exhibited hallmark signatures reminiscent of a macrophage subset that positively regulates hematopoietic stem cell generation. Our findings provide a valuable cross-species resource, advancing our understanding of human pre-circulation yolk sac hematopoiesis and offering a theoretical basis for the regeneration of functional blood cells.

The inability of articular cartilage to self-repair following injuries frequently precipitates osteoarthritis, profoundly affecting patients' quality of life. Given the limitations inherent in current clinical interventions, an urgent need exists for more effective cartilage regeneration methodologies. Previous studies have underscored the potential of electrical stimulation in cartilage repair, thus motivating the investigation of innovative strategies. The present study introduces a three-dimensional scaffold fabricated through a composite technique that leverages the synergy between piezoelectricity and biofactors to enhance cartilage repair. This scaffold is composed of polylactic acid (PLLA) and barium titanate (BT) for piezoelectric stimulation and at the bottom with a collagen-coated layer infused with fibroblast growth factor-18 (FGF-18) for biofactor delivery. Designed to emulate the properties of natural cartilage, the scaffold enables controlled generation of piezoelectric charges and the sustained release of biofactors. In vitro tests confirm that the scaffold promotes chondrocyte proliferation, matrix hyperplasia, cellular migration, and the expression of genes associated with cartilage formation. Moreover, in vivo studies on rabbits have illustrated its efficacy in catalyzing the in situ regeneration of articular cartilage defects and remodeling the extracellular matrix. This innovative approach offers significant potential for enhancing cartilage repair and holds profound implications for regenerative medicine.

A simple cavity-based technology capable of simultaneously measuring optical rotary dispersion and circular dichroism within milliseconds offers ultra-high sensitivity and unprecedented spectral resolution. This advancement holds significant potential for various biochemical applications, including drug development, clinical diagnosis, and food science and safety., (© 2024. The Author(s).)

Objective: To put forward a new index of cervical curvature evaluation - relative cervical curvature area, and a new classification of cervical spine was proposed according to the relative cervical curvature area., Methods: A total of 167 subjects with cervical spondylosis were included in the study. Firstly, 119 subjects were selected to measure C2-C7 lordosis angle by Cobb angle method, Harrison posterior tangent method, and Jackson physiological stress line method, and then their relative cervical curvature area, C1-C7 Cobb angle, C7 slope, and T1 slope were measured. The correlation between relative cervical curvature area and 3 measurement methods and common sagittal parameters was analyzed. According to the angle classification method, we calculated the diagnostic boundary value of the relative cervical curvature area classification, and selected 48 subjects to evaluate its diagnostic efficacy. Finally, 119 subjects were re-evaluated according to the diagnostic threshold and the number of intersections to verify the feasibility of the new classification., Results: The results showed that the relative cervical curvature area index had good intraobserver and interobserver repeatability. Relative cervical curvature area was correlated with Harrison posterior tangent method (r = 0.930), Cobb angle method (r = 0.886), and Jackson physiological stress line method (r = 0.920), and correlated with C1-C7 Cobb angle, C7 slope, and T1 slope. The relative cervical curvature area has a good diagnostic performance for distinguishing patients with lordosis, straightening, and kyphosis. According to the new classification of cervical spine, 119 subjects were divided into 57 simple lordosis, 11 simple straightening, 4 simple kyphosis, 26 S-type, and 21 RS-type., Conclusions: The relative cervical curvature area uses the area parameter instead of the original angle parameter and distance parameter to incorporate the change of segmental curvature, which makes up for the shortcomings of the Cobb angle method that only evaluates the curvature of 2 vertebrae, and better reflects the cervical curvature. Studies have shown that relative cervical curvature area has good repeatability and diagnostic value, and found that it has a good correlation with common cervical sagittal parameters. The new classification of cervical spine makes up for the disadvantage that the angle classification method cannot distinguish between S-type and RS-type, and initially proposes to use the number of intersections and the relative absolute value area to reflect the severity of S-type., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

With the widespread vaccination of COVID-19 vaccine, a few cases have been reported that COVID-19 vaccine may cause endocrine disorders. A 59-y-old man presented with a loss of appetite after the first COVID-19 vaccination, which resolved spontaneously after 3 d. After the second COVID-19 vaccination, the symptoms including the loss of appetite, nausea, and vomiting reappeared and worsened along with loss of vision. He was found to have severe hyponatremia, and further investigations revealed secondary adrenal insufficiency, secondary hypothyroidism and Rathke's cleft cyst. The patient responded well to glucocorticoid and levothyroxine supplementation, and at 1-y follow-up the patient developed hypogonadism. We hypothesize that hypophysitis is probably induced by COVID-19 vaccine and report the rare but serious adverse reactions for early recognition and intervention.

Hematopoietic stem progenitor cells (HSPCs) are derived from a specialized subset of endothelial cells named hemogenic endothelial cells (HECs) via a process of endothelial-to-hematopoietic transition during embryogenesis. Recently, with the usage of multiple single-cell technologies and advanced genetic lineage tracing techniques, namely, "TIF" approaches that combining transcriptome, immunophenotype and function/fate analyses, massive new insights have been achieved regarding the cellular and molecular evolution underlying the emergence of HSPCs from embryonic vascular beds. In this review, we focus on the most recent advances in the enrichment markers, functional characteristics, developmental paths, molecular controls, and the embryonic site-relevance of the key intermediate cell populations bridging embryonic vascular and hematopoietic systems, namely HECs and pre-hematopoietic stem cells, the immediate progenies of some HECs, in mouse and human embryos. Specifically, using expression analyses at both transcriptional and protein levels and especially efficient functional assays, we propose that the onset of Kit expression is at the HEC stage, which has previously been controversial., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the Chinese Medical Association (CMA) and Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College (IHCAMS).)

The vast bulk of polystyrene (PS), a major type of plastic polymers, ends up in landfills, which takes up to thousands of years to decompose in nature. Chemical recycling promises to enable lower-energy pathways and minimal environmental impacts compared with traditional incineration and mechanical recycling. Herein, we demonstrated that methanol as a hydrogen supplier assisted the depolymerization of PS (denoted as PS-MAD) into alkylbenzenes over a heterogeneous catalyst composed of Ru nanoparticles on SiO 2 . PS-MAD achieved a high yield of liquid products which accounted for 93.2 wt % of virgin PS at 280 °C for 6 h with the production rate of 118.1 mmol carbon  g catal. -1  h -1 . The major components were valuable alkylbenzenes (monocyclic aromatics and diphenyl alkanes), the sum of which occupied 84.3 wt % of liquid products. According to mechanistic studies, methanol decomposition dominates the hydrogen supply during PS-MAD, thereby restraining PS aromatization which generates by-products of fused polycyclic arenes and polyphenylenes., (© 2024 Wiley-VCH GmbH.)

With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in improving cancer prognosis, but a series of immune-related adverse events (irAEs), including immune-related endocrine events (irEEs), caused by ICIs have also aroused concerns. Rapid clinical identification of irAEs caused by ICIs is particularly important. We describe a case of secondary adrenocortical insufficiency (AI) after PD-1 treatment in a postoperative patient with endometrial cancer. A 73-year-old female patient developed anorexia, nausea, vomiting, malaise, electrolyte disturbances, ineffective symptomatic treatment, and decreased serum adrenocorticotropin and cortisol levels six months after retifanlimab treatment. The vomiting resolved, and the electrolyte levels were corrected after 3 days of treatment with glucocorticoids (hydrocortisone, intravenous, 200 mg/day). When patients present with gastrointestinal symptoms, such as poor appetite and nausea, not only symptomatic treatment but also a search for the etiology behind the symptoms is needed, especially in immunotherapy patients who should undergo a thorough evaluation of the endocrine system and be alert for adrenocortical insufficiency., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Xiao, Zhou, Zhu, Bi, Du and Zhang.)

Background: Symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) present significant challenges for military pilots, which may result in grounding if not effectively managed. Surgical treatment for LDH and LIS may offer a pathway to return to flight duty (RTFD), but recent data on this crucial topic is lacking. This study seeks to address this gap by investigating the RTFD outcomes among Chinese military pilots who have undergone lumbar spine surgery for symptomatic LDH and LIS., Methods: A retrospective review was conducted on active-duty military pilots who underwent isolated decompressive or fusion procedures at an authorized military medical center from March 1, 2007, to March 1, 2023. The analysis utilized descriptive statistics to examine demographic, occupational, surgical, and outcome data, with a particular focus on preoperative flight status, recommended clearance by spine surgeons, and actual RTFD outcomes and time., Results: Among the identified cases of active-duty military pilots with LDH or LIS treated by lumbar surgery (n = 24), 70.8% (17 of 24) consistently maintained RTFD status without encountering surgical complications or medical issues during the follow-up period. Of the seven pilots who did not RTFD, one retired within a year of surgery, two had anterior cruciate ligament injuries, three had residual radicular symptoms, and one had chronic low back pain. Excluding pilots who retired and did not RTFD for reasons unrelated to their lumbar conditions, the RTFD rate stood at 81.0% (17 of 21). The median time for recommended clearance by spine surgeons was 143.0 days (inter-quartile range, 116.5-196.0), while the median duration for actual RTFD attainment was 221.0 days (inter-quartile range, 182.0-300.0). The median follow-up post-lumbar surgery was 1.7 years (inter-quartile range, 0.4-2.9)., Conclusion: Most military pilots diagnosed with symptomatic LDH and LIS can continue their careers and regain active-duty flight status following lumbar spine surgery, as reflected by the high RTFD rate. Lumbar spine surgery can successfully alleviate the physical constraints associated with spinal conditions, facilitating the return of military pilots to their demanding profession., (© 2024. The Author(s).)

INTRODUCTION: There is no consensus on whether cardiopulmonary reserve affects the risk of gravity-induced loss of consciousness (G-LOC) or almost loss of consciousness (A-LOC). Few previous studies have used cardiopulmonary exercise testing (CPET) to assess cardiopulmonary reserve function (CPRF) of fighter aviators. We compared CPET-related parameters in G-LOC/A-LOC and non-G-LOC/A-LOC fighter aviators to explore the effect of cardiopulmonary reserve function on G tolerance. METHODS: A total of 264 male fighter aviators with more than 500 h of flight experience participated in the study, all of whom underwent CPET and human centrifuge testing. We divided the aviators into two groups based on whether they experienced G-LOC/A-LOC during the human centrifuge test and compared the CPET parameters between the two groups. RESULTS: A total of 37 aviators (14%) experienced G-LOC/A-LOC. There were no significant differences in age (26.65 ± 4.30 vs. 26.01 ± 4.95), height (173.68 ± 4.21 vs. 173.55 ± 3.37), weight (69.51 ± 6.22 vs. 69.63 ± 6.01), or body mass index (23.06 ± 2.11 vs. 23.11 ± 1.82) between the two groups. Forced vital capacity (FVC) (4.95 ± 0.87 vs. 4.65 ± 0.79) and forced expiratory volume in 1 s (FEV 1 ) divided by FVC (FEV 1 /FVC) (79.88 ± 7.24 vs. 83.72 ± 9.24) of pulmonary function of the G-LOC/A-LOC group was significantly lower than that of the non-G-LOC/A-LOC group. There was no significant difference in CPET-related parameters between the two groups. DISCUSSION: In conclusion, FEV 1 /FVC may be a factor affecting aviators' G-LOC/A-LOC, meaning aviators with slightly lower ventilation are more likely to experience G-LOC/A-LOC. However, oxygen uptake and exercise blood pressure, oxygen pulse, etc., may not be the main factors influencing G-LOC/A-LOC. Lan X, Zhu W, Du J, Wang J, Yang M, Xu Y, Cao Y. High G tolerance and cardiopulmonary reserve function in healthy air force aviators . Aerosp Med Hum Perform. 2023; 94(12):911-916.

There are limitations and difficulties in the management of traditional in-person standardized patient (SP) practice. The latest developments in online communication tools and the COVID-19 pandemic have promoted the needs for online clinical skills training objectively. However, existing commercial online platforms may not meet the requests for SP-based medical simulation. This paper described the methodology applied to develop a smartphone-based online platform for the management of clinical skills training and assessment with remote SPs, and aimed to determine whether this new platform is acceptable or useful through a pilot run in September 2020. The post-run survey including questionnaire inspired by technological acceptance model and determinants of the perceived ease of use was used to assess the acceptability and usefulness of the platform. Twenty four-year students of clinical medicine participated in the pilot study with twenty SPs and ten faculties. Data from the post-run survey showed that there was a general recognition that the platform is easy to use among all the users. Two questions regarding the usefulness of the platform showed significant differences between the SPs/faculties and the students. More SPs found the platform useful as a training method than the students did. The faculties showed more attempts than the students to use this platform for clinical skills training in the future. This smartphone-based online platform was widely accepted among the tested students, SPs and faculties, which meets the requests and challenges of the new era. It provides an effective approach for clinical skills training and assessment with remote SPs.

Background: Mitochondrial dysfunction and subsequent cardiomyocyte apoptosis significantly contribute to pressure overload-induced heart failure (HF). A highly oxidative environment leads to mitochondrial damage, further exacerbating this condition. Asiatic acid (AA), a proven antioxidant and anti-hypertrophic agent, might provide a solution, but its role and mechanisms in chronic pressure overload-induced HF remain largely unexplored., Methods: We induced pressure overload in mice using transverse aortic constriction (TAC) and treated them with AA (100 mg/kg/day) or vehicle daily by oral gavage for 8 weeks. The effects of AA on mitochondrial dysfunction, oxidative stress-associated signaling pathways, and overall survival were evaluated. Additionally, an in vitro model using hydrogen peroxide-exposed neonatal rat cardiomyocytes was established to further investigate the role of AA in oxidative stress-induced mitochondrial apoptosis., Results: AA treatment significantly improved survival and alleviated cardiac dysfunction in TAC-induced HF mice. It preserved mitochondrial structure, reduced the LVW/BW ratio by 20.24%, mitigated TAC-induced mitochondrial-dependent apoptosis by significantly lowering the Bax/Bcl-2 ratio and cleaved caspase-9/3 levels, and attenuated oxidative stress. AA treatment protected cardiomyocytes from hydrogen peroxide-induced apoptosis, with concurrent modulation of mitochondrial-dependent apoptosis pathway-related proteins and the JNK pathway., Conclusions: Our findings suggest that AA effectively combats chronic TAC-induced and hydrogen peroxide-induced cardiomyocyte apoptosis through a mitochondria-dependent mechanism. AA reduces cellular levels of oxidative stress and inhibits the activation of the JNK pathway, highlighting its potential therapeutic value in the treatment of HF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A meta-analysis research was executed to appraise the consequence of intrawound vancomycin powder (IWVP) in orthopaedic surgery (OPS) as surgical site wound infection (SSWI) prophylaxis. Inclusive literature research till March 2023 was carried out and 2756 interconnected researches were revised. Of the 18 picked researches enclosed 13 214 persons with OPS were in the used researches' starting point, 5798 of them were utilising IWVP, and 7416 were control. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to appraise the consequence of the IWVP in OPS as SSWI prophylaxis by the dichotomous approaches and a fixed or random model. IWVP had significantly lower SSWIs (OR, 0.61; 95% CI, 0.50-0.74, P < .001), deep SSWIs (OR, 0.57; 95% CI, 0.36-0.91, P = .02), and superficial SSWIs (OR, 0.67; 95% CI, 0.46-0.98, P = .04) compared with control in persons with OPS. IWVP had significantly lower SSWIs, deep SSWIs, and superficial SSWIs compared with control in persons with OPS. However, when interacting with its values, caution must be taken and more research is needed to confirm this finding., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Wang, Zhang, Xie, Zhao, Gan, Li, Zhang, Chen, Li, Huang, Chen and Du.)

Fresh-cut potato browning is a severe problem in the potato processing industry. Ascorbic acid, L-cysteine, hydrogen sulfide (H 2 S), and nitric oxide (NO) have been reported to reduce the browning in fresh-cut vegetables and fruits. We compared the effect of each food additive at its commonly used concentration on fresh-cut potato browning in order to choose a highly efficient treatment and explore its mechanism. Fresh-cut potato slices were immersed in 0.3 mmol L -1 ascorbic acid, 0.7 mmol L -1  L-cysteine, 0.7 mmol L -1 H 2 S, or 2.0 mmol L -1 NO for 10 min and stored at 4°C until the measurements finished. Results showed that the ascorbic acid and L-cysteine treatments showed less browning than the control treatment, while the H 2 S and NO treatments did not. Ascorbic acid increased total phenolic content, polyphenol oxidase (PPO) and peroxidase (POD) activities, while L-cysteine decreased PPO and POD activities with no change in total phenolic content. In addition, these two treatments did not influence respiration rate, weight loss, or rot index. In conclusion, ascorbic acid (0.3 mmol L -1 ) and L-cysteine (0.7 mmol L -1 ) can be valuable means to control fresh-cut potato browning. Ascorbic acid inhibits the browning mainly by reducing quinones back to phenolic compounds, but L-cysteine inhibits the browning mainly by decreasing PPO and POD activities., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Prior to the generation of hematopoietic stem cells (HSCs) from the hemogenic endothelial cells (HECs) mainly in the dorsal aorta in midgestational mouse embryos, multiple hematopoietic progenitors including erythro-myeloid progenitors and lymphoid progenitors are generated from yolk sac HECs. These HSC-independent hematopoietic progenitors have recently been identified as major contributors to functional blood cell production until birth. However, little is known about yolk sac HECs. Here, combining integrative analyses of multiple single-cell RNA-sequencing datasets and functional assays, we reveal that Neurl3-EGFP, in addition to marking the continuum throughout the ontogeny of HSCs from HECs, can also serve as a single enrichment marker for yolk sac HECs. Moreover, while yolk sac HECs have much weaker arterial characteristics than either arterial endothelial cells in the yolk sac or HECs within the embryo proper, the lymphoid potential of yolk sac HECs is largely confined to the arterial-biased subpopulation featured by the Unc5b expression. Interestingly, the B lymphoid potential of hematopoietic progenitors, but not for myeloid potentials, is exclusively detected in Neurl3-negative subpopulations in midgestational embryos. Taken together, these findings enhance our understanding of blood birth from yolk sac HECs and provide theoretical basis and candidate reporters for monitoring step-wise hematopoietic differentiation., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Surgically treated anterior cruciate ligament (ACL) injuries may be a waivable condition and allow return to full flight status, but waivers are based on expert opinion rather than recent published data. The purpose of this study was to evaluate return to flight after anterior cruciate ligament reconstruction (ACLR) in male military aircrews with ACL injuries and to identify factors that affect flight clearance., Method: A single-center retrospective review was conducted by the authors for all active-duty aircrew who underwent ACLR at an authorized military medical center from January 2010 to December 2019. Demographic characteristics, occupational information, surgical data, and flight readiness evaluation outcomes were collected. Based on the final medical evaluation, subjects were divided into a qualified group ( N  = 64) and a disqualified group ( N  = 9), and the difference in data collected between the two groups was then analyzed to identify factors affecting flight clearance., Results: A total of 73 patients underwent successful ACLR with a mean age of 31.6 ± 5.6 years. Non-contact injury was the main type of ACL injury, accounting for 84.9% of the total injuries. 55 cases (75.3%) occurred during daily sports activities and 18 (24.7%) during military training. 64 of the 73 crewmembers (87.7%) were able to return to flight at their last follow-up evaluation. The preoperative interval time (PIT) was significantly less in the qualified group than in the disqualified group ( P  = 0.002). Patients who underwent ACLR within three months were more likely to return to flying than those who underwent the procedure three months later (97.4% vs. 76.5%, P  = 0.010). The incidence of failure to return to flight duty was significantly higher in aircrews with ACL injuries combined with meniscal injuries than in aircrews with isolated ACL injuries (21.4% vs. 0.0%, P  = 0.017)., Conclusion: ACLR appears to be safe for military aircrew suffering ACL injuries with or without meniscal injury, and return to flight status is the most likely outcome for the majority of postoperative pilots. Prolonged PIT, PIT > 3 months, and ACL injury combined with meniscus injury had a negative impact on postoperative flight readiness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhang, Yang, Xie, Chen, Peng, Chen, Li, Huang, Xue and Du.)

Plastic pollution is a planetary threat that has been exacerbated by the COVID-19 pandemic due to the surge in medical waste, personal protective equipment and takeaway packaging. A socially sustainable and economically viable method for plastic recycling should not use consumable materials such as co-reactants or solvents. Here we report that Ru nanoparticles on zeolitic HZSM-5 catalyse the solvent- and hydrogen-free upcycling of high-density polyethylene into a separable distribution of linear (C 1 to C 6 ) and cyclic (C 7 to C 15 ) hydrocarbons. The valuable monocyclic hydrocarbons accounted for 60.3 mol% of the total yield. Based on mechanistic studies, the dehydrogenation of polymer chains to form C=C bonds occurs on both Ru sites and acid sites in HZSM-5, whereas carbenium ions are generated on the acid sites via the protonation of the C=C bonds. Accordingly, optimizing the Ru and acid sites promoted the cyclization process, which requires the simultaneous existence of a C=C bond and a carbenium ion on a molecular chain at an appropriate distance, providing high activity and cyclic hydrocarbon selectivity., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To investigate the association between false lumen (FL) dependency of segmental arteries (SAs) at T9-L3 levels and the risk of spinal cord injury (SCI) following total arch replacement and frozen elephant trunk (FET) implantation in the setting of acute DeBakey type I aortic dissection (AAD)., Methods: The study involved consecutive patients with AAD who underwent total arch replacement and FET implantation between 2020 and 2022. Primary outcome was postoperative SCI. The inverse probability of treatment weighting (IPTW) method was employed to minimize the impact of no-randomization bias. Antegrade placement of FET was followed by end-to-end anastomosis of a 4-branch arch graft at the proximal landing site of FET., Results: A total of 146 patients were included (age, 50.5 ± 11.7 years, 115 male), of whom 35 (24%) had SAs at T9-L3 levels completely dependent on FL (FL-dependency group). There was no significant difference in early (30-day or in-hospital) mortality rates between FL-dependency (14.3%) and FL-independency (18.0%) groups ( P  = .80), however, the rate of SCI was significantly higher in the FL-Dependency group (34.3% vs 2.7%, P  < .001). After adjustments, FL dependency was associated with a significantly increased risk of SCI (odds ratio, 13.1; 95% confidence interval, 4.2-41.0; P  < .001), whereas it was not significantly associated with risks of early mortality or other major complications ( P = .16-.98)., Conclusions: FL dependency of SAs at the T9-L3 levels was significantly associated with the development of SCI following FET implantation in AAD, warning against its uses on patients presenting with FL dependency of SAs at critical segments., (© 2023 The Author(s).)

Bone metastasis of liver cancer leads to a worse prognosis with no appropriate treatment clinically. Exosomes are associated with tumor bone metastasis. This study aimed to investigate the effects of liver cancer cell-derived exosomes on bone metastasis. Exosomes were isolated from Hep3B cells, and the effects of osteoclast differentiation were assessed using TRAP assay. The expression of OPG and RANKL was assessed using qRT-PCR. The interaction of miR-574-5p and BMP2 was analyzed using luciferase reporter analysis, RNA pull-down, and qRT-PCR. We found that Hep3B cells promoted osteoclast differentiation of RANKL-induced Raw264.7 cells by secreting exosomes, with decreased OPG and increased RANKL expression. The exosomes were isolated from Hep3B cells, which promoted osteoclast differentiation. Exosomal miR-574-5p promoted osteoclastogenesis by targeting BMP2. Moreover, exosomes facilitated osteoclast differentiation, promoting bone metastasis by regulating miR-574-3p in vivo. In conclusion, liver cancer cell-derived exosomal miR-574-5p promoted osteoclastogenesis by regulating BMP2, thereby promoting bone metastasis in vivo. The findings suggest that liver cancer cell-released exosomes are the potential therapeutic approach for bone metastatic liver cancer. DATA AVAILABILITY STATEMENT: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interests., (Copyright © 2023. Published by Elsevier GmbH.)

Advanced functional materials with fascinating properties and extended structural design have greatly broadened their applications. Metamaterials, exhibiting unprecedented physical properties (mechanical, electromagnetic, acoustic, etc.), are considered frontiers of physics, material science, and engineering. With the emerging 3D printing technology, the manufacturing of metamaterials becomes much more convenient. Graphene, due to its superior properties such as large surface area, superior electrical/thermal conductivity, and outstanding mechanical properties, shows promising applications to add multi-functionality into existing metamaterials for various applications. In this review, the aim is to outline the latest developments and applications of 3D printed graphene-based metamaterials. The structure design of different types of metamaterials and the fabrication strategies for 3D printed graphene-based materials are first reviewed. Then the representative explorations of 3D printed graphene-based metamaterials and multi-functionality that can be introduced with such a combination are further discussed. Subsequently, challenges and opportunities are provided, seeking to point out future directions of 3D printed graphene-based metamaterials., (© 2023 Wiley-VCH GmbH.)

Extra-heavy olefins (C 12+ = ), feedstocks to synthesize a wide range of value-added products, are conventionally generated from fossil resources via energy-intensive wax cracking or multi-step processes. Fischer-Tropsch synthesis with sustainably obtained syngas as feed-in provides a potential way to produce C 12+ = , though there is a trade-off between enhancing C-C coupling and suppressing further hydrogenation of olefins. Herein, we achieve selective production of C 12+ = via the overall conversion of CO and water, denoted as Kölbel-Engelhardt synthesis (KES), in polyethylene glycol (PEG) over a mixture of Pt/Mo 2 N and Ru particles. KES provides a continuously high CO/H 2 ratio, thermodynamically favoring chain propagation and olefin formation. PEG serves as a selective extraction agent to hinder hydrogenation of olefins. Under an optimal condition, the yield ratio of CO 2 to hydrocarbons reaches the theoretical minimum, and the C 12+ = yield reaches its maximum of 1.79 mmol with a selectivity (among hydrocarbons) of as high as 40.4%., (© 2023. The Author(s).)

Aiming at the poor robustness and adaptability of traditional control methods for different situations, the deep deterministic policy gradient (DDPG) algorithm is improved by designing a hybrid function that includes different rewards superimposed on each other. In addition, the experience replay mechanism of DDPG is also improved by combining priority sampling and uniform sampling to accelerate the DDPG's convergence. Finally, it is verified in the simulation environment that the improved DDPG algorithm can achieve accurate control of the robot arm motion. The experimental results show that the improved DDPG algorithm can converge in a shorter time, and the average success rate in the robotic arm end-reaching task is as high as 91.27%. Compared with the original DDPG algorithm, it has more robust environmental adaptability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dong, Du, Liu, Heidari and Chen.)

Objective: To compare the clinical efficacy of the minimally invasive technique and the open method in the treatment of irreducible unilateral subaxial cervical facet joint dislocation (SCFD)., Methods: From March 2015 to September 2018, 62 patients with unilateral SCFD were studied. The cases were divided into 2 groups based on different surgery strategies. Thirty-one patients were enrolled in the minimally invasive surgery (MIS) group, and 31 patients were enrolled in the open surgery group. The duration of prone position operation, blood loss, and total hospitalization costs were recorded. The clinical effects were evaluated using visual analogue scale scores, the Oswestry Disability Index, and Japanese Orthopedic Association scores at each follow-up. In addition, the segmental Cobb angle and intervertebral height were recorded and compared., Results: The amount of intraoperative blood loss, prone position operation duration, and total hospital costs in the MIS group were significantly lower than in the open surgery group. The visual analogue scale, Oswestry Disability Index, and Japanese Orthopedic Association scores of the 2 groups significantly improved after the operation. A satisfactory fusion rate was obtained in both groups, and the segmental Cobb angle and intervertebral height scores in both groups improved significantly., Conclusions: Minimally invasive reduction had equal clinical efficacy to posterior open surgery. However, MIS was less invasive and had lower costs. Therefore, it is a potential option in the treatment of SCFD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose of the Study: Understanding self-directed learning (SDL) when using point of care information systems (POCIS) can inform educational providers of the usefulness of the system for continuing medical education (CME). Sen's capability approach can offer a unique perspective to understand SDL, which considers the extent to which individual valued learning needs can be achieved. The aim of the study was to pilot the use of a questionnaire informed by the capability approach for understanding SDL when using POCIS in the context of CME., Methods: A semi-structured questionnaire aligned to the capability approach (Capability Approach for SDL with POCIS Questionnaire - CA-SPQ) in the context of CME was developed and implemented with 200 users of a POCIS (BMJ Best Practice)., Results: The response rate was 92 and 78% of users considered that their valued outcomes were achieved and that they could apply their new learning to practice. The questionnaire had high content, face, and construct validity., Conclusion: The CA-SPQ can offer a practical instrument to provide data and useful information for understanding SDL, when using POCIS in the context of CME. It also has the potential for adaptation to other areas of medical education.

It remains challenging to determine the regions of metastasis to lymph nodes during operation for clinical stage I non-small cell lung cancer (NSCLC). This study aimed to establish intraoperative mathematical models with nomograms for predicting the hilar-intrapulmonary node metastasis (HNM) and the mediastinal node metastasis (MNM) in patients with clinical stage I NSCLC. The clinicopathological variables of 585 patients in a derivation cohort who underwent thoracoscopic lobectomy with complete lymph node dissection were retrospectively analyzed for their association with the HNM or the MNM. After analyzing the variables, we developed multivariable logistic models with nomograms to estimate the risk of lymph node metastasis in different regions. The predictive efficacy was then validated in a validation cohort of 418 patients. It was confirmed that carcinoembryonic antigen (>5.75 ng/mL), CYFRA211 (>2.85 ng/mL), the maximum diameter of tumor (>2.75 cm), tumor differentiation (grade III), bronchial mucosa and cartilage invasion, and vascular invasion were predictors of HNM, and carcinoembryonic antigen (>8.25 ng/mL), CYFRA211 (>2.95 ng/mL), the maximum diameter of tumor (>2.75 cm), tumor differentiation (grade III), bronchial mucosa and cartilage invasion, vascular invasion, and visceral pleural invasion were predictors of MNM. The validation of the prediction models based on the above results demonstrated good discriminatory power. Our predictive models are helpful in the decision-making process of specific therapeutic strategies for the regional lymph node metastasis in patients with clinical stage I NSCLC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The acidity of Chinese dwarf cherry [ Cerasus humilis (Bge.) Sok.] fruits is a key factor affecting the sensory quality of fruits, and it undergoes great changes during development. The molecular mechanisms of these changes are still unclear. In this study, fruits of high-acid 'Nongda4' and low-acid 'DS-1' varieties of Chinese dwarf cherry were used to determine the acid content at different developmental stages. We used transcriptome profiles to identify key genes related to organic acid metabolism and construct their co-expression networks, and we studied the expression patterns of key genes in 36 Chinese dwarf cherry accessions. The titratable acid content of both 'DS-1' and 'Nongda4' fruits first increased and then decreased during fruit development; however, the titratable acid content of 'DS-1' fruits changed to a minor extent. The organic acid content of 'Nongda4' was significantly higher than that of 'DS-1'. The organic acids in mature fruits were mainly malic acid and citric acid. Analysis of the differentially expressed genes related to organic acid metabolism revealed six key genes, including two MDH genes, one tDT gene, one ME gene, one PEPCK gene, and one VHA gene. Weighted gene co-expression network association analysis revealed four modules that were significantly correlated with organic acid content, and 10 key genes with high connectivity among these four modules were screened, including two PK genes, two MDH genes, two ME genes, one PEPCK gene, one VHA gene, one PEPC gene, and one tDT gene. According to the expression patterns of genes in different Chinese dwarf cherry accessions, seven genes were confirmed to represent key genes related to the regulation of organic acids during Chinese dwarf cherry fruit development. These results provide a foundation for further studies on the molecular mechanism of organic acid accumulation in Chinese dwarf cherry fruit., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Wang, Zhang, Guo, Mu and Du.)

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., (© 2022 Institute of Food Technologists.)

Accurate detection of severe acute respiratory syndrome coronavirus 2 is not only necessary for viral load monitoring to optimize treatment in hospitalized coronavirus disease 2019 patients, but also critical for deciding whether the patient could be discharged without any risk of viral shedding. Digital droplet PCR (ddPCR) is more sensitive than reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and is usually considered the superior choice. In the current study, we compared the clinical performance of RT-qPCR and ddPCR using oropharyngeal swab samples from patients hospitalized in the temporary Huoshenshan Hospital, Wuhan, Hubei, China. Results demonstrated that ddPCR was indeed more sensitive than RT-qPCR. Negative results might be caused by poor sampling technique or recovered patients, as the range of viral load in these patients varied significantly. In addition, both methods were highly correlated in terms of their ability to detect all three target genes as well as the ratio of copies of viral genes to that of the IC gene. Furthermore, our results evidenced that both methods detected the N gene more easily than the ORF gene. Taken together, these findings imply that the use of ddPCR, as an alternative to RT-qPCR, is necessary for the accurate diagnosis of hospitalized coronavirus disease 2019 patients., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Endothelial oxidative stress and inflammation attributable to the activation of a Nox2-NADPH oxidase are key features of many cardiovascular diseases. Here, we report a novel small chemical compound (LMH001, MW = 290.079), by blocking phosphorylated p47 phox interaction with p22 phox , inhibited effectively angiotensin II (AngII)-induced endothelial Nox2 activation and superoxide production at a small dose (IC50 = 0.25 μM) without effect on peripheral leucocyte oxidative response to pathogens. The therapeutic potential of LMH001 was tested using a mouse model (C57BL/6J, 7-month-old) of AngII infusion (0.8 mg/kg/d, 14 days)-induced vascular oxidative stress, hypertension and aortic aneurysm. Age-matched littermates of p47 phox knockout mice were used as controls of Nox2 inhibition. LMH001 (2.5 mg/kg/d, ip. once) showed no effect on control mice, but inhibited completely AngII infusion-induced excess ROS production in vital organs, hypertension, aortic walls inflammation and reduced incidences of aortic aneurysm. LMH001 effects on reducing vascular oxidative stress was due to its inhibition of Nox2 activation and was abrogated by knockout of p47 phox . LMH001 has the potential to be developed as a novel drug candidate to treat oxidative stress-related cardiovascular diseases., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Most nurses in China have not been trained to take care of end-of-life patients appropriately due to lack of educational resources and insufficient training. A palliative care program was launched by the Jiangsu Nursing Association (JNA training program) and to identify gaps in palliative care training. The main aim of this study was to evaluate the training effects of the JNA training program on nurses' knowledge and attitudes to palliative care., Methods: A cross-sectional study was conducted with 10 048 registered nurses in all regions of Jiangsu. All participants completed an online questionnaire using the Chinese version of The Palliative Care Quiz for Nursing (PCQN-C) and the Frommelt Attitude Toward Care of the Dying scale (FATCOD-B-C). A propensity score matched analysis was performed between the nurses who had attended the JNA training program and whose who hadn't., Results: The average score of PCQN-C among all nurses was 8.79, while the mean score of the FATCOD-B-C was 103.62. Those participants who attended the JNA training program had significantly better scores than those who did not. Propensity score matching analysis showed that the palliative care training program failed to improve nurses' knowledge in psychosocial and spiritual care or their attitudes towards the necessity of family support although there was positive impact on other aspects of palliative care., Conclusions: Knowledge of palliative care among Chinese nurses remains low. Training programs may improve general knowledge and attitudes to palliative care. However, important aspects of knowledge such as communication skills, family support, and psychosocial aspects of care, are missing. These gaps should be filled in future palliative care training programs targeting nurses with oriental culture background., (© 2022. The Author(s).)

Purpose: The aim of this study is to visualize and analyze the research hot pots in radiation therapy for rectal cancer and provide researchers with a clear and visual reference for subsequent studies. Methods: The literature scientometric analysis about "external beam radiation therapy (EBRT) for rectal cancer" was made through the WoSCC (2010 to 2019). And the data was visualized and analyzed by the Microsoft Office Excel (2019) and CiteSpace (V. 5.7.R1). Results: 4,263 relevant articles were downloaded. The number of published articles per year has been increasing (2010-2020). The United States published the highest number of articles. The UK has the strongest partnerships with other countries/regions. Leiden University has the highest number of published articles and University Texas MD Anderson Cancer Center has extensive collaborations with other academic institutions. The number of articles published in the Diseases of the Colon Rectum is the most, and the Journal of Clinical Oncology is the most cited. 27 articles became the strongest burst citations lasting until 2020. In recent years, a lot of research has been done on "watch and wait", "short-course radiotherapy", "MRI", "neoadjuvant radiotherapy, "MRI in rectal cancer", "chemotherapy regimen improvement", "adding adjuvant chemotherapy", and so on. Conclusion: The current research hot pots may be the "watch and wait", "short-course radiotherapy", "MRI", "neoadjuvant chemoradiotherapy", "MRI in rectal cancer", "chemotherapy regimen improvement", and "adding adjuvant chemotherapy"., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Intervertebral disc degeneration (IDD) has caused great trouble in people's lives. Dysregulated long noncoding RNAs (lncRNAs) are closely linked to IDD progression. Our study aims to analyze the role of LINC00917 in the progression of IDD. Forty nucleus pulposus (NP) IDD tissues and 40 NP tissues of intervertebral discs without apparent degeneration were collected. TBHP was used to induce IDD. Cell proliferation was measured using the MTT and EdU assays. Pyroptosis was detected using flow cytometry. RT-qPCR and Western blot assays were performed to determine mRNA, miRNA, and protein expression. Dual-luciferase reporter and RNA pull-down assays were performed to verify the relationship between LINC00917 or NLRP1 and miR-149-5p. LINC00917 expression was enhanced in TBHP-treated nucleus pulposus cells (NPCs). The knockdown of LINC00917 promoted proliferation and inhibited cytotoxicity, inflammatory response, and pyroptosis of NPCs. LINC00917 functions as a sponge for miR-149-5p. Having silenced miR-149-5p, the effects of LINC00917 knockdown on NPC proliferation and inflammation-induced pyroptosis were alleviated. NLRP1 overexpression induced cellular dysfunction and pyroptosis of NPCs. LINC00917 knockdown restored NPC cellular functions and inhibited IDD progression by modulating the miR-149-5p/NLRP1 axis.

Tumor metastasis is directly correlated to poor prognosis and high mortality. Circulating tumor cells (CTCs) play a pivotal role in metastatic cascades, of which CTC clusters is highly metastatic compared to single CTCs. Although platelets and neutrophils within the bloodstream could further exacerbate the pro-metastatic effect of single CTCs, the influence of platelets and neutrophils on CTC clusters mediated metastasis remains unclear. In this study, a pro-metastatic complex composed of CTC clusters, platelets and neutrophils, namely circulating tumor microemboli (CTM), was identified in vivo among different metastatic tumor, which was demonstrated with highly upregulation of hypoxia-inducible factor-1α (HIF-1α). While knock-out of HIF-1α or therapeutically downregulating of HIF-1α via HIF-1α inhibitor (BAY87-2243)-loaded neutrophil cyto-pharmaceuticals (PNEs) could efficiently restrain CTM mediated lung metastasis. The underlying mechanism of metastasis inhibition was attributed to the downregulation of HIF-1α-associated PD-L1, which would enhance immune response for inhibiting metastatic cells. Thus, our work here illustrates that hypoxia was an essential factor in promoting CTM colonization in lung. More importantly, we provide a promising strategy by targeted downregulation of HIF-1α in CTM via neutrophil cyto-pharmaceuticals for treatment of CTM mediated metastasis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We report that cardiac fibroblasts (CFs) and mesenchymal progenitors are more hypoxic than other cardiac interstitial populations, express more hypoxia-inducible factor 1α (HIF-1α), and exhibit increased glycolytic metabolism. CF-specific deletion of Hif-1a resulted in decreased HIF-1 target gene expression and increased mesenchymal progenitors in uninjured hearts and increased CF activation without proliferation following sham injury, as demonstrated using single-cell RNA sequencing (scRNA-seq). After myocardial infarction (MI), however, there was ∼50% increased CF proliferation and excessive scarring and contractile dysfunction, a scenario replicated in 3D engineered cardiac microtissues. CF proliferation was associated with higher reactive oxygen species (ROS) as occurred also in wild-type mice treated with the mitochondrial ROS generator MitoParaquat (MitoPQ). The mitochondrial-targeted antioxidant MitoTEMPO rescued Hif-1a mutant phenotypes. Thus, HIF-1α in CFs provides a critical braking mechanism against excessive post-ischemic CF activation and proliferation through regulation of mitochondrial ROS. CFs are potential cellular targets for designer antioxidant therapies in cardiovascular disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Low back pain is one of the most serious public health problems worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The key pathological change during IVDD is dysfunction of the annulus fibrosus (AF). However, due to the lack of an in-depth understanding of AF biology, the methods to reconstruct the AF are very limited. In this study, the mice AF cell atlas were decoded by single-cell RNA sequencing to provide a guide for AF reconstruction. The results first identify a new population of AF cells, fibrochondrocyte-like AF cells, which synthesize both collagen I and collagen II and are potential functional cells for AF reconstruction. According to the dual features of the AF extracellular matrix, a composite hydrogel based on the acylation of methacrylated silk fibroin with methacrylated hyaluronic acid was produced. To obtain the ability to stimulate differentiation, the composite hydrogels were combined with a fibrochondrocyte-inducing supplement. Finally, reconstruction of the AF defects, by the novel AF stem cell-loaded composite hydrogel, could be observed, its amount of chondroid matrices recovered to 31.7% of AF aera which is significantly higher than that in other control groups. In summary, this study decodes the AF cell atlas, based on which a novel strategy for AF reconstruction is proposed., Competing Interests: The authors declare that they have no competing financial interests or personal relationships that could have appeared influence the work reported in the paper., (© 2022 The Authors.)

Calcification of the bicuspid aortic valve (BAV) involves differential expression of various RNA genes, which is achieved through complex regulatory networks that are controlled in part by transcription factors and microRNAs. We previously found that miR-195-5p regulates the osteogenic differentiation of valvular interstitial cells (VICs) by targeting the TGF-β pathway. However, the transcriptional regulation of miR-195-5p in calcified BAV patients is not yet clear. In this study, stenotic aortic valve tissues from patients with BAVs and tricuspid aortic valves (TAVs) were collected. Candidate transcription factors of miR-195-5p were predicted by bioinformatics analysis and tested in diseased valves and in male porcine VICs. SP2 gene expression and the corresponding protein levels in BAV were significantly lower than those in TAV, and a low SP2 expression level environment in VICs resulted in remarkable increases in RNA expression levels of RUNX2, BMP2, collagen 1, MMP2, and MMP9 and the corresponding proteins. ChIP assays revealed that SP2 directly bound to the transcription promoter region of miR-195-5p. Cotransfection of SP2 shRNA and a miR-195-5p mimic in porcine VICs demonstrated that SP2 repressed SMAD7 expression via miR-195-5p, while knockdown of SP2 increased the mRNA expression of SMAD7 and the corresponding protein and attenuated Smad 2/3 expression. Immunofluorescence staining of diseased valves confirmed that the functional proteins of osteogenesis differentiation, including RUNX2, BMP2, collagen 1, and osteocalcin, were overexpressed in BAVs. In Conclusion, the transcription factor Sp2 is expressed at low levels in VICs from BAV patients, which has a negative impact on miR-195-5p expression by binding its promoter region and partially promotes calcification through a SMAD-dependent pathway., (Copyright © 2021. Published by Elsevier Inc.)

The gene activity underlying cell differentiation is regulated by a diverse set of transcription factors (TFs), histone modifications, chromatin structures and more. Although definitive hematopoietic stem cells (HSCs) are known to emerge via endothelial-to-hematopoietic transition (EHT), how the multi-layered epigenome is sequentially unfolded in a small portion of endothelial cells (ECs) transitioning into the hematopoietic fate remains elusive. With optimized low-input itChIP-seq and Hi-C assays, we performed multi-omics dissection of the HSC ontogeny trajectory across early arterial ECs (eAECs), hemogenic endothelial cells (HECs), pre-HSCs and long-term HSCs (LT-HSCs) in mouse embryos. Interestingly, HSC regulatory regions are already pre-configurated with active histone modifications as early as eAECs, preceding chromatin looping dynamics within topologically associating domains. Chromatin looping structures between enhancers and promoters only become gradually strengthened over time. Notably, RUNX1, a master TF for hematopoiesis, enriched at half of these loops is observed early from eAECs through pre-HSCs but its enrichment further increases in HSCs. RUNX1 and co-TFs together constitute a central, progressively intensified enhancer-promoter interactions. Thus, our study provides a framework to decipher how temporal epigenomic configurations fulfill cell lineage specification during development., (© 2022. The Author(s).)

Chip-level spectrometers provide a stable and cost-effective solution for spectral analysis in various applications. Here we present a silicon on-chip digital Fourier transform spectrometer consisting of eight cascaded optical switches connected by delay waveguides. By configuring the states of the optical switches, this chip can realize 127 Mach-Zehnder interferometers with linearly increased optical path differences. A machine-learning regularization method is utilized to reconstruct the spectrum. Experimental results show that our chip can retrieve both sparse and broadband optical spectra with negligible reconstruction errors. The spectral resolution can be further improved by cascading more stages of optical switches. Our method has the advantages of compact size, high scalability, and high signal-to-noise ratio, making it a promising candidate for realizing miniaturized spectrometers.

During embryogenesis, hematopoietic stem progenitor cells (HSPCs) are believed to be derived from hemogenic endothelial cells (HECs). Moreover, arterial feature is proposed to be a prerequisite for HECs to generate HSPCs with lymphoid potential. Although the molecular basis of hematopoietic stem cell-competent HECs has been delicately elucidated within the embryo proper, the functional and molecular characteristics of HECs in the extraembryonic yolk sac (YS) remain largely unresolved. In this study, we initially identified six molecularly different endothelial populations in the midgestational YS through integrated analysis of several single-cell RNA sequencing (scRNA-seq) datasets and validated the arterial vasculature distribution of Gja5 + ECs using a Gja5-EGFP reporter mouse model. Further, we explored the hemogenic potential of different EC populations based on their Gja5-EGFP and CD44 expression levels. The hemogenic potential was ubiquitously detected in spatiotemporally different vascular beds on embryonic days (E)8.5-E9.5 and gradually concentrated in CD44-positive ECs from E10.0. Unexpectedly, B-lymphoid potential was detected in the YS ECs as early as E8.5 regardless of their arterial features. Furthermore, the capacity for generating hematopoietic progenitors with in vivo lymphoid potential was found in nonarterial as well as arterial YS ECs on E10.0-E10.5. Importantly, the distinct identities of E10.0-E10.5 HECs between YS and intraembryonic caudal region were revealed by further scRNA-seq analysis. Cumulatively, these findings extend our knowledge regarding the hemogenic potential of ECs from anatomically and molecularly different vascular beds, providing a theoretical basis for better understanding the sources of HSPCs during mammalian development., (© 2021. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Soils are a repository for polychlorinated biphenyls (PCBs). A pot incubation experiment was performed with four soils (black soil, paddy soil, oasis soil, and fluvo-aquic soil) treated with Aroclor 1242 to achieve PCB concentrations of 5 mg kg -1 . The soil enzyme activities of protease, phosphatase, catalase, dehydrogenase, and laccase were determined by spectrophotometry. The soil bacterial communities were investigated using Illumina sequencing analysis. The results showed that the characteristics of the test soils varied among the soil types. The fluvo-aquic soil had the greatest PCB dissipation rate (86.41%), followed by the oasis (79.31%), paddy (56.09%), and black (50.65%) soils. The soil pH, cation exchange capacity, soil organic matter content, and particle diameter played significant roles in PCB dissipation from soils. The soil type had a greater influence than PCB contamination on the soil enzyme activities and bacterial communities (alpha diversity, community structure, and composition). Among the four soils, the bacterial communities of the fluvo-aquic soil were the most susceptible to PCB contamination. However, the bacterial communities of the black soil were not changed by PCB contamination., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

Three human adenovirus (HAdV) genotypes, HAdV-7, HAdV-14, and HAdV-55, emerged as the most prevalent variants in China over the past decade and caused both sporadic, fatal cases and frequent, large outbreaks. Early diagnosis is essential to control infections and endemics. Here, we established a loop-mediated isothermal amplification (LAMP) assay coupled with an instrument-free nucleic acid extraction device recently developed by our group; the assay could detect all the 3 prevalent HAdV genotypes. Specificity analysis showed no cross-reactivity with other common respiratory pathogens and the analytical sensitivity was as low as 10 copies/μL. All detection steps could be completed within 1 hour. The assay's performance was evaluated using clinical samples and compared with the gold standard RT-PCR method, showing highly consistent results. The LAMP assay developed here could be readily used in basic laboratory facilities and with minimal DNA extraction equipment, and as a reliable screening test in a resource-limited setting., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To propose a novel deep-learning-based auto-segmentation model for CTV delineation in cervical cancer and to evaluate whether it can perform comparably well to manual delineation by a three-stage multicenter evaluation framework., Methods: An adversarial deep-learning-based auto-segmentation model was trained and configured for cervical cancer CTV contouring using CT data from 237 patients. Then CT scans of additional 20 consecutive patients with locally advanced cervical cancer were collected to perform a three-stage multicenter randomized controlled evaluation involving nine oncologists from six medical centers. This evaluation system is a combination of objective performance metrics, radiation oncologist assessment, and finally the head-to-head Turing imitation test. Accuracy and effectiveness were evaluated step by step. The intra-observer consistency of each oncologist was also tested., Results: In stage-1 evaluation, the mean DSC and the 95HD value of the proposed model were 0.88 and 3.46 mm, respectively. In stage-2, the oncologist grading evaluation showed the majority of AI contours were comparable to the GT contours. The average CTV scores for AI and GT were 2.68 vs. 2.71 in week 0 ( P = .206), and 2.62 vs. 2.63 in week 2 ( P = .552), with no significant statistical differences. In stage-3, the Turing imitation test showed that the percentage of AI contours, which were judged to be better than GT contours by ≥5 oncologists, was 60.0% in week 0 and 42.5% in week 2. Most oncologists demonstrated good consistency between the 2 weeks ( P > 0.05)., Conclusions: The tested AI model was demonstrated to be accurate and comparable to the manual CTV segmentation in cervical cancer patients when assessed by our three-stage evaluation framework., Competing Interests: Authors SW, QC, and YC were employed by the company MedMind Technology Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Chen, Guan, Zhen, Shen, Liu, Liu, Li, Geng, You, Wang, Li, Zhang, Chen, Du, Chen, Chen, Wang, Zhang and Qiu.)

It remains challenging to treat tumor metastasis currently in the light of multiple cascade processes of tumor metastasis. Additionally, multiple clinical drugs for metastasis have quite limited therapeutic potential and even facilitate metastasis in preclinical models. Thus, potential metastasis targets and novel metastasis-directed drugs are urgently needed to be further developed. Herein, transforming growth factor-β (TGF-β) is verified to contribute to lung metastasis in a context-dependent manner in the 4T1 orthotopic tumor-bearing mice model, which induces epithelial-mesenchymal-transition (EMT) to promote tumor dissemination from the primary site and dampens the anti-tumor response of neutrophils to support tumor colonization at the metastatic niche. In view of neutrophils' superior tropism towards both inflammatory primary tumor and metastatic niche, SB525334, a TGF-β receptor inhibitor, is loaded into cationic liposome (SBLP) which is subsequently incorporated into neutrophils to yield the cyto-pharmaceuticals (SBLP/NE). The systemically infused SBLP/NE can simultaneously migrate into both primary and metastatic sites, then release SB525334 in response to tumor stimuli, and contextually inhibit TGF-β-mediated-EMT and phenotype reversal of infiltrated neutrophils, showing substantial metastasis suppression efficacy without causing any detectable toxicities. This project shifts the paradigm for metastasis suppression therapy by simultaneous blockage of contextual TGF-β using metastatic-cascades-targeting neutrophil cyto-pharmaceuticals., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We rigorously calculate the conservative gradient force (GF) and the non-conservative scattering force (SF) associated with the optical tweezers (the single beam optical trap). A wide range of parameters are considered, with particle size ranging from the Rayleigh to Mie regime (radius ∼3 µm), dielectric constant ranging from metallic (large and negative) to high dielectrics (large and positive), numerical aperture (NA) ranging from 0.5 to 1.33, and different polarizations. The trap depth associated with GF can reach 123 and 168 k B T per mW for a 0.5 µm-radius polystyrene particle illuminated by a 1064 nm Gaussian beam with NA = 0.9 and 1.3, respectively. This indicates that unless at a low beam power or with a small NA, the Brownian fluctuations do not play a role in the stability. The transverse GF orthogonal to beam propagation always dominates over the transverse SF. While the longitudinal SF can be larger than the longitudinal GF when the scattering is strong, the NA is small, or when absorption is present, optical trapping under these conditions is difficult. Generally speaking, absorption reduces GF and enhances SF, while increasing a dielectric constant enhances GF slightly but boosts SF significantly owing to stronger scattering. These results verify previous experimental observations and explain why optical tweezers are so robust across such a wide range of conditions. Our quantitative calculations will also provide a guide to future studies.

This study aimed to investigate the mental health status of nurses from low-risk areas of novel coronavirus (COVID-19) pandemic, its potential impact factors, and the main stressors under the normalized prevention and control in China. A mobile phone app-based survey was conducted among registered nurses in Jiangsu province via a region-stratified sampling method. The questionnaire consisted of items on the demographic characteristics of the nursing staff and their Depression, Anxiety, Stress Scale-21 (DASS-21) along with questions for self-assessment of stressors that are associated with COVID-19. STROBE guideline was used. Among 1803 nurses who were working in the low-risk areas in Jiangsu, 22.0%, 29.8%, and 16.1% of them reported moderate to extreme levels of depression, anxiety, and stress, respectively. Having 11-15 years of working experience and being a fixed-term contract nurse were associated with experiencing worse mental health outcomes while supporting-Wuhan working experience and having mental health preparation course training were independent factors that had beneficial impact on their psychological well-being afterward. In terms of source of pressure, a key finding of this study is that the main stressor among these nurses was the lack of patient's understanding and cooperation (71.2%) which calls for better psychosocial communication between nurses and patients. The present findings would provide information for other regions at low risk of COVID-19 and may aid the provision of support and interventions for the benefit of the psychological well-being of nurses who are exposed to life-threatening occupational risks and are more vulnerable to the pandemic than others., (© 2021 John Wiley & Sons Australia, Ltd.)

Lectin receptor-like protein kinases (LecRLKs) have been shown to be involved in plants' responses to various biotic and abiotic stresse factors. Cerasus humilis is an important fruit species widely planted for soil and water conservation in northern China due to its strong tolerance to drought and salinity stresses. In this study, a total of 170 LecRLK family genes (125 G-types, 43 L-types and 2 C-types) were identified in the newly released whole-genome sequences of C. humilis. Furthermore, nine representative LecRLK genes in young plants of C. humilis under varying drought and salinity stresses were selected for qRT-PCR analysis. Our systematic comparative analyses revealed the active participation of these nine LecRLK genes in the salt and drought stress responses of C. humilis. The results from our study have provided a solid foundation for future functional verification of these LecRLK family genes and will likely help facilitate the more rapid and effective development of new stress resistant Cerasus humilis cultivars., Competing Interests: The authors have declared that no competing interests exist.