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Abstract The North Pacific is known with iron limitation for phytoplankton growth in the subarctic region and nitrogen limitation in the subtropical gyre. Although the growth rate of phytoplankton is determined by the concentration of limiting nutrient, the supply ratio of iron to nitrogen is suggested to be essential to this biogeographic pattern. However, the underlying dynamics determining the ratio remain largely unknown. We investigated mechanisms of dissolved iron (dFe) and nitrate (NO3−) transport to the euphotic zone of the North Pacific using an eddy‐resolvable biogeochemical model. We show that lateral advection and atmospheric deposition are dominant drivers for dFe transport, resulting in high Fe:N supply ratio in both subarctic and subtropical regions. Conversely, significant vertical supplies of NO3− through upwelling and diffusion processes markedly reduce the supply ratio in the subarctic region. These dynamics combined lead to high Fe:N supply ratio in the gyre and low ratio in the subarctic, ultimately driving high nitrogen fixation condition in the gyre and the iron‐limited phytoplankton growth condition in the subarctic region.

There are many potential approaches to marine carbon dioxide removal (mCDR), of which ocean iron fertilization (OIF) has the longest history of study. However, OIF studies to date were not primarily designed to quantify the durability of carbon (C) storage, nor how wise OIF might be as an mCDR approach. To quantify C sequestration, we introduce a metric called the “centennial tonne,” defined as 1,000 kg of C isolated from atmospheric contact for on average at least 100 years. We present the activities needed to assess OIF from a scientific and technological perspective, and additionally, how it might be responsibly studied and potentially deployed. The five activities include: field studies in the Northeast Pacific; improved modeling for field studies, data assimilation and predictions at larger scales; improvements in monitoring, reporting and verification (MRV) for C, and also MRV for tracking ecological and environmental impacts; and developing new iron sources and their delivery, to increase efficiencies and reduce costs. The fifth activity is to understand whether public and community support exists for OIF, and what governance structures might support further research and possible deployment of OIF. This article is written by a multidisciplinary experts group called Exploring Ocean Iron Solutions (ExOIS) that is organized around a responsible code of conduct. Of the mCDR approaches, OIF has the potential to be low cost, scalable, and rapidly deployable. Reducing CO2 emissions must lead the way, but there is also an urgency to decide under what conditions and whether OIF might be deployed or not.

Objectives There is no consensus on the treatment of moderate‐to‐severe rigid scoliosis. Anterior release and three‐column osteotomy are excessively traumatic, whereas posterior column osteotomy (PCO) alone results in poor outcomes. An emerging surgical technique, posterior intervertebral release (PR), can release the rigid spine from the posterior approach. This study was performed to compare the multi‐segment apical convex PR combined with PCO and PCO alone in patients with moderate‐to‐severe rigid scoliosis. Methods From June 2021 to June 2022, this prospective study of moderate‐to‐severe (Cobb: 70–90°) rigid scoliosis (flexibility of main curve

Abstract Oceanic submesoscale processes are ubiquitous in the North Pacific Subtropical Gyre (NPSG), where the biological carbon pump is generally ineffective. Due to difficulties in collecting continuous observations, however, it remains uncertain whether episodic submesoscale processes can drive significant changes in particulate organic carbon (POC) export into the mesopelagic ocean. Here we present observations from high-frequency Biogeochemical-Argo floats in the NPSG, which captured the enhanced POC export fluxes during the intensifying stages of a submesoscale front and a cyclonic eddy compared to their other life stages. A higher percentage of POC export flux was found to be transferred to the base of mesopelagic layer at the front compared to that at the intensifying eddy and the mean of previous studies (37% vs. ~10%), suggesting that the POC export efficiency was significantly strengthened by submesoscale dynamics. Such findings highlight the importance of submesoscale fronts for carbon export and sequestration in subtropical gyres.

Abstract Objective To compare clinical and radiological outcomes of multi-fold rib and structural iliac bone grafts, the primary autologous graft techniques in anterolateral-only surgery for single-segment thoracic and thoracolumbar spinal tuberculosis. Methods This retrospective study included 99 patients treated from January 2014 to March 2022, categorized into 64 with multi-fold rib grafts (group A) and 35 with structural iliac bone grafts (group B). Outcomes assessed included hospital stay, operation time, intraoperative blood loss, postoperative drainage, complications, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the Visual Analog Scale (VAS) for pain, the Oswestry Disability Index (ODI), bone fusion time, and the American Spinal Injury Association (ASIA) impairment scale grade. Segmental kyphotic angle and intervertebral height were measured radiologically before surgery and follow-up. Results The mean follow-up was 63.50 ± 26.05 months for group A and 64.97 ± 26.43 months for group B (P > 0.05). All patients had achieved a clinical cure. Group A had a shorter operation time (P = 0.004). Within one week post-surgery, group B reported higher VAS scores (P 0.05). However, group A showed a greater segmental kyphotic angle at the final follow-up, while group B had better maintenance of kyphotic angle correction and intervertebral height (P 0.05). Conclusions Multi-fold rib grafts resulted in shorter operation times and less postoperative pain, while structural iliac bone grafts provided better long-term maintenance of spinal alignment and stability, suggesting their use in cases where long-term outcomes are critical.

PurposePrevious studies have confirmed the advantages and disadvantages of autogenous iliac bone and nano-hydroxyapatite/polyamide 66 (n-HA/PA66) cage. However, there is no conclusive comparison between the efficacy of the two implant materials in spinal tuberculosis bone graft fusion. The aim of this study was to analyze the mid-to long-term clinical and radiologic outcomes between n-HA/PA66 cage and autogenous iliac bone for anterior reconstruction application of spinal defect for thoracolumbar tuberculosis.MethodsWe retrospectively reviewed all patients who underwent anterior debridement and strut graft with n-HA/PA66 cage or iliac bone combined with anterior instrumentations between June 2009 and June 2014. One-to-one nearest-neighbor propensity score matching (PSM) was used to match patients who underwent n-HA/PA66 cage to those who underwent iliac bone. Clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) and visual analogue score (VAS). Radiographic evaluations included cage subsidence and segmental angle.ResultsAt the end of the PSM analysis, 16 patients from n-HA/PA66 cage group were matched to 16 patients in Iliac bone group. The C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values in the n-HA/PA66 group decreased significantly from 33.19 ± 10.89 and 46.63 ± 15.65 preoperatively, to 6.56 ± 2.48 and 9.31 ± 3.34 at the final follow-up, respectively (p < 0.001). There were no significant differences in the CRP and ESR values between the two groups at the final follow-up. The VAS and JOA scores in the iliac bone and n-HA/PA66 group were significantly improved at the 3-month follow-up postoperatively (both p < 0.001). Then, improvements of VAS and JOA scores continue long at final follow-up. However, there were no significant differences in the VAS and JOA scores at any time point between the two groups (p > 0.05). Although the segmental angle (SA) significantly increased after surgery in both groups, there was no significant difference at any time point after surgery (p > 0.05). There were no significant differences in the cage subsidence and fusion time between the two groups.ConclusionOverall, our data suggest that the n-HA/PA66 cage outcomes are comparable to those in the autogenous iliac bone, with a similar high fusion rate as autogenous iliac bone.

Objectives The three‐dimensional printing titanium (3DPT) cage with excellent biomechanical properties and osseointegration capabilities has been initially used in spinal fusion, while the polyetheretherketone (PEEK) cage, a bioinert material device, has been a widely used for decades with relatively excellent clinical outcomes. This study was performed to investigate the early radiographic and clinical outcomes of 3DPT cage versus PEEK cage in patients undergoing anterior cervical discectomy and fusion (ACDF) and transforaminal lumbar interbody fusion (TLIF). Methods This prospective controlled trial, from December 2019 to June 2022, included patients undergoing ACDF and TLIF with 3DPT cages and compared them to patients using PEEK cages for treating spinal degenerative disorders. The outcome measures included radiographic parameters (intervertebral height [IH], subsidence, fusion status, and bone‐cage interface contact) and clinical outcomes (Japanese Orthopaedic Association [JOA], Neck Disability Index [NDI], Oswestry Disability Index [ODI], Short Form 12‐Item Survey [SF‐12], Visual Analog Scale [VAS], and Odom's criteria). Student's independent samples t test and Pearson's chi‐square test were used to compare the outcome measures between the two groups before surgery and at 1 week, 3 and 6 months after surgery. Results For the patients undergoing ACDF, the 3DPT (18 patients/[26 segments]) and PEEK groups (18 patients/[26 segments]) had similar fusion rates at 3 months and 6 months follow‐up (3 months: 96.2% vs. 83.3%, p = 0.182; 6 months: 100% vs. 91.7%, p = 0.225). The subsidence in the 3DPT group was significantly lower than that in the PEEK group (3 months: 0.4 ± 0.2 mm vs. 0.9 ± 0.7 mm p = 0.004; 6 months: 0.7 ± 0.3 mm vs. 1.5 ± 0.8 mm, p

Objectives Decreased bone mineral density (BMD) is associated with complications in implantation surgery for severe spinal deformity. In this quantitative study, we aimed to investigate the impact of halo‐pelvic traction on vertebral bone mineral density (BMD) and identify the risk factors for a decrease in BMD. Methods Patients who underwent halo‐pelvic traction at our hospital between 2019 and 2022 were included in the study. Patients’ data, including height, weight, and BMD pre‐ and post‐traction, were collected and analyzed. Quantitative computed tomography (QCT) was used to determine the BMD. The paired rank sum test was used to evaluate the changes in each measurement parameter. Linear regression was used to identify risk factors for a decrease in BMD. Results Fifteen patients were included in the study, nine women and six men, with an average age of 21.2 ± 7.3 years. Eleven patients had severe rigid scoliosis, while four had tuberculotic kyphosis. One expert measured the BMD values of 345 vertebrae using QCT. The average traction time was 143.3 ± 44.4 days. The average pre‐traction BMD was 183.1 ± 73.8 mg/cm3, and the average post‐traction BMD was 140.5 ± 61.3 mg/cm3 (p

Objective At present, the influence of Modic changes (MCs) on postoperative fusion rate of lumbar interbody fusion (LIF) is mainly focused on the medium‐ and long‐term fusion rate, while the short‐term fusion rate has not been reported. The aim of this study was to compare the short‐term fusion rate of lumbar degenerative disease patients with and without MCs after single level transforaminal lumbar interbody fusion (TLIF). Methods In this retrospective and matched‐pair case control study, we included 100 patients who underwent TLIF from January 2017 to January 2020 and had at least two follow‐up visits over a two‐year period. Fifty patients with MCs (MCs group) were matched with 50 patients without MCs (non MCs group) for age, sex, surgical level, diagnosis, operative time, and intraoperative blood loss. We collected the X‐ray and computed tomography (CT) data of patients from 3 months to 2 years after the operation to assess bony fusion and the cage union ratio. According to the type of cage, the MCs group was further divided into the nano‐hydroxyapatite/polyamide 66 (n‐HA/PA66) group and polyetheretherketone (PEEK) group, and the fusion performance between the two groups was compared. Finally, age, sex, body mass index (BMI), smoking and cage type were included in the logistic regression model for risk factor analysis. Results The bony fusion rates in the MCs group at 3 months, 6 months, 1 year and 2 years after surgery were significantly lower than those in the non MCs group (P

ObjectiveThis retrospective monocentric study was conducted to evaluate the clinical and radiological outcomes of the nano-hydroxyapatite/polyamide66 (n-HA/PA66) cage in reconstructing the anterior column of the spine following total en bloc spondylectomy (TES).MethodsA cohort of 24 patients, 20 diagnosed with primary malignant tumors and 4 with metastatic malignancies, was selected based on specific inclusion criteria. All were subjected to TES and anterior column reconstruction with the n-HA/PA66 cage from January 2013 to July 2023 at a single institution. Pre-operative embolization was performed on all patients. Documented factors included operation duration, intraoperative blood loss, length of hospital stay, treatment history, and involved level. Mechanical complications and radiological parameters such as the local kyphotic angle (LKA), anterior vertebral height (AVH), posterior vertebral height (PVH), cage subsidence, and bone fusion time were evaluated. Quality of life and neurological function were gauged using tools like the Visual Analog Scale (VAS), Eastern Cooperative Oncology Group (ECOG) performance score, Karnofsky Performance Score (KPS) scale, and American Spinal Injury Association (ASIA) grading.ResultsAll patients were followed up for 12–127 months, with an average period of 39.71 months. An average operation time of approximately 8.57 h and a blood loss volume of about 1,384 ml were recorded. No instances of tumor recurrence or multiple organ metastases were reported, though recurrence was detected in 2 living patients. Solid fusion was achieved in all patients at a mean time of 6.76 ± 0.69 months. Cage breakage or migration was not observed. Subsidence into the adjacent vertebral bodies was identified in 3 patients but was deemed clinically irrelevant. Significant improvements in VAS, ECOG performance score, KPS scale, and ASIA scores were noted from pre- to post-surgery (P 0.05).ConclusionThe integration of TES and the n-HA/PA66 cage was found to yield promising clinical and radiological outcomes in anterior column spine reconstruction. The use of this material did not hinder oncological care, including the provision of adjuvant treatments (chemo/radiotherapy), ultimately contributing to the enhanced long-term quality of life for spinal tumor patients.

Abstract Nutrient stoichiometry (e.g., nitrate + nitrite to soluble reactive phosphorus, refer to N + N/SRP, N/P hereafter) governs growth, competition and niche partitioning of phytoplankton in the illuminated oceans. The N/P, however, varies widely across the ocean and the underlying mechanisms remain unclear. Here, we report direct observations of significant variations in N/P in response to different life stages of two cyclonic eddies observed in the western South China Sea. High N/P (19.1 ± 6.9) values were observed around the nitracline in a mature-stage eddy, whereas a decay-stage eddy was characterized with low N/P (14.4 ± 4.1). The elevated N/P ratios accompanied by enriched fucoxanthin (pigment for diatom) and biogenic silica around the nitracline suggest that eddy pumping enhanced the growth of diatom which preferentially uptakes P relative to N in the mature stage of the eddy. Such high N/P ratios in the upper ocean could be reproduced if diatom uptake ratio was set between 10 and 16 in a data constrained numerical model. The preferential P uptake by enhanced diatom growth might reduce the P supply to the surface ocean, which is critical for N2-fixers. The transient changes in nutrient stoichiometry associated within the life cycle of cyclonic eddies also challenges the parameterization of physical–biogeochemical models with fixed phytoplankton uptake stoichiometry ratios, which could lead to bias of the model output for phytoplankton dynamics in oligotrophic ocean, where eddies frequently occur.

Abstract The mechanism that determines the dynamics of subsurface chlorophyll maximum depth (zSCM) has long been debated. Although a coupling between zSCM and the top of nitracline (znit) has been widely observed in the open ocean, a co‐location of zSCM and an isolume depth (ziso) has often been reported in oligotrophic waters. In this study, based on continuous observations of ten BGC‐Argo floats, we found that the seasonal displacement of zSCM in all subtropical gyres was driven mainly by light, but zSCM displayed a nutrient‐driven pattern occasionally when znit became shallower than ziso. We therefore proposed a “two‐group competition framework”: zSCM in subtropical gyres is determined by the competition of two phytoplankton groups, nutrient‐sensitive picoeukaryotes and light‐sensitive Prochlorococcus. When znit (ziso) is shallower than ziso (znit), picoeukaryotes (Prochlorococcus) dominate the chlorophyll biomass at the SCM, and thus zSCM follows znit (ziso). This paradigm reconciles the inconsistent conclusions drawn from earlier studies.

Background Because of the severity and fatal outcome of traumatic vertical atlantoaxial dislocation (AAD), most patients may die in the early post‐traumatic period. The post‐injury management of patients with vertical AAD has been rarely reported. Improper treatment may lead to disastrous outcome and further aggravate the neurologic symptoms. Case Presentation This report describes the perioperative management and outcome of a rare improperly treated patient with traumatic vertical AAD. The severe pulmonary infection of this patient prevented further surgery for vertical AAD. After placement of a halo vest, combined with effective antibiotic drug treatment, the patient's pulmonary infection was brought under control. The patient underwent atlantoaxial fusion using C1 lateral mass screws and C2 pedicle screws with the assistance of the halo vest. A computed tomography scan at 1 year follow‐up indicated that the bone graft was fused and the patient was able to walk independently. Conclusion Skull traction is contraindicated in patients with traumatic vertical AAD. Application of a halo vest can be used for temporary fixation of the cervical spine and atlantoaxial fixation should be performed to maintain the stability of atlantoaxial articulation.

Abstract An unprecedented warm sea surface temperature (SST) anomaly event, namely, the Blob, occurred in the northeast Pacific during the winter (October–January) of 2013/2014, causing substantial economic and ecological impacts. Here, we explore the driving forces of the Blob from both atmospheric and oceanic perspectives and show that the Blob primarily resulted from weak wintertime cooling due to the reduced air-sea heat flux transfer from the ocean to the atmosphere and the reduced horizontal advection of cold water in the upper ocean. Both mechanisms were attributed to an anomalous high-pressure system over the study region. Specifically, the anomalous air-sea heat flux, which was dominated by turbulent heat flux anomalies, was mainly induced by the increased air temperature (i.e., with a contribution of approximately 70%) and the weakened wind speed associated with the high-pressure system. The reduced horizontal heat advection was mainly due to the weakened winds acting on the ocean temperature meridional gradient. Using a regional ocean numerical model with different experimental runs, we evaluated the contributions of air temperature and wind drivers to the Blob at both the surface and subsurface of the ocean. The Blob was absent when the model was forced by climatology-air-temperature. Both the SST and integrated ocean heat content (OHC, 0–150 m) decreased, and the mixed layer depth (MLD) was deeper than that in the control run forced by real atmospheric conditions. In the climatology-winds experiment, obvious warm anomalies still existed, which were similar to but weaker than the control run. The SST (OHC) and MLD values in the climatology-winds run were between those of the climatology-air-temperature run and the control run. Compared to former studies that attribute the formation of the Blob to an anomalous air-sea heat flux and horizontal advection mainly induced by reduced winds, our study demonstrates that anomalous warm air temperatures played a more important role in its formation.

Background: Lymphocyte-activation gene 3 (LAG-3), a checkpoint molecule contributing to immune suppressive microenvironment, is regarded as a promising target in cancer treatment. SHR-1802 is a novel anti-LAG-3 monoclonal antibody. Objectives: To evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of SHR-1802. Design: A phase I dose-escalation and expansion trial of SHR-1802 in patients with advanced solid tumors. Methods: Patients with confirmed advanced solid tumors who failed previous standard-of-care or for whom no effective therapy was available were enrolled to receive SHR-1802 once every 21-day cycle. Dose escalation was performed in an accelerated titration design followed by a 3 + 3 scheme at escalating doses from 0.3 to 10 mg/kg. On the basis of results from dose-escalation phase, one or two dose levels were expanded to establish the recommended phase II dose (RP2D). The primary end points were dose-limiting toxicity (DLT) and RP2D. Results: Between 01 July 2020, and 07 September 2021, 28 patients were enrolled. No DLTs were observed, and all doses investigated were well tolerated. Treatment-related adverse events occurred in 20 patients (71.4%), all grade 1 or 2, with the most common ones being anemia (14.3%), asthenia (14.3%), electrocardiogram QT prolonged (14.3%), followed by increased blood fibrinogen (10.7%), infusion-related reaction (10.7%), and hypoalbuminemia (10.7%). No adverse event-related discontinuation occurred. Three patients died from adverse events, but none of the deaths were deemed related to study treatment. SHR-1802 exposure enhanced with the increasing doses in a greater than dose-proportional manner over the investigated dose range. The disease control rate was 32.0% (95% CI 14.9%–53.5%). The median progression-free survival was 2.0 months (95% CI 1.2–6.1). Conclusions: SHR-1802 demonstrated a tolerable safety profile and preliminary antitumor activity in patients with advanced solid tumors. Further studies with larger sample size and in combination forms are warranted for future clinical application. Registration ClinicalTrials.gov: NCT04414150

Bone tuberculosis, an extrapulmonary manifestation of tuberculosis, presents unique treatment challenges, including its insidious onset and complex pathology. While advancements in anti-tubercular therapy have been made, the efficacy is often limited by difficulties in achieving targeted drug concentrations and avoiding systemic toxicity. The intricate bone structure and presence of granulomas further impede effective drug delivery. Nano-drug delivery systems have emerged as a promising alternative, offering the enhanced targeting of anti-tubercular drugs. These systems, characterized by their minute size and adaptable surface properties, can be tailored to improve drug solubility, stability, and bioavailability, while also responding to specific stimuli within the bone TB microenvironment for controlled drug release. Nano-drug delivery systems can encapsulate drugs for precise delivery to the infection site. A significant innovation is their integration with prosthetics or biomaterials, which aids in both drug delivery and bone reconstruction, addressing the infection and its osteological consequences. This review provides a comprehensive overview of the pathophysiology of bone tuberculosis and its current treatments, emphasizing their limitations. It then delves into the advancements in nano-drug delivery systems, discussing their design, functionality, and role in bone TB therapy. The review assesses their potential in preclinical research, particularly in targeted drug delivery, treatment efficacy, and a reduction of side effects. Finally, it highlights the transformative promise of nanotechnology in bone TB treatments and suggests future research directions in this evolving field.

BackgroundThe distal adding-on phenomenon has attracted extensive discussion in the field of spine surgery due to the continual occurrence after scoliosis correction. Previous work has mainly focused on adolescent idiopathic scoliosis (AIS), and a relatively high number of theories for the mechanism of the distal adding-on phenomenon has been proposed for these kinds of patients. Severe and rigid scoliosis, as a special disease form, has a unique etiology, clinical manifestations and internal mechanisms distinct from those of AIS. Given the uniqueness of this disease, the mechanism and causes of the distal adding-on phenomenon have been infrequently studied in depth.ObjectiveTo define clinical and radiological factors associated with distal adding-on in patients with severe and rigid scoliosis.MethodsRadiographic parameters and demographic data of patients with severe and rigid scoliosis were evaluated preoperatively, after posterior instrumentation and fusion surgery, and at the final follow-up via radiographs. According to the appearance of distal adding-on at the final follow-up, the patients were grouped into the Adding-on and the Non-adding-on groups. Various radiological parameters were analyzed in stepwise multivariate logistic regression to identify the variables associated with distal adding-on, which were then incorporated into a nomogram. The predictive performance and calibration of the nomograms for distal adding-on were assessed using C statistics and calibration plots.Results93 patients (21 in the Adding-on and 72 in the Non-adding-on group) were included. The incidence of distal adding-on was 22.6%. The variables associated with distal adding-on were the anterior release, posterior internal distraction, and later posterior spinal fusion (IP) procedure, the posterior vertebral column resection and posterior spinal fusion (PVCR) procedure, postoperative apical vertebral translation (Post-AVT) and preoperative slope of the line linking the pedicles on the concave side of the upper- and lower-end vertebrae (Tan α). Combining these factors, the nomogram achieved a concordance index of 0.92 in predicting distal adding-on and had well-fitted calibration curves.ConclusionsFor patient with a negative Tanα in severe and rigid scoliosis, the risk of distal adding-on tended to increase, and it is recommended to give priority to IP or PVCR. In the final correction, a smaller Post-AVT should not be pursued excessively.

Phytoplankton, the dominant marine primary producers, are considered highly sensitive indicators of ecosystem conditions and changes. The East China Sea (ECS) includes a variety of oceanic and coastal domains that collectively challenge our understanding of phytoplankton dynamics and controls. This study evaluates the seasonal and interannual variability of phytoplankton in the ECS and the underlying environmental determinants based on 22-year satellite chlorophyll (Chl-a) data and concurrent environmental variables. A seasonal spring bloom was found in the ECS, classically driven by increased stratification, which is associated with increases in sea surface temperature (SST), photosynthetically available radiation (PAR), net heat flux (NHF), and reduced wind mixing. The most significant Chl-a interannual variability was present in a triangular area surrounded by three SST fronts in the southern ECS during springtime. Anomalously high Chl-a (~30% increase) occurred with increased SST and NHF and enhanced wind mixing during negative Pacific Decadal Oscillation (PDO) and El Niño–Southern Oscillation (ENSO) modes. This seems to be contrary to the stratification control model, which fits the seasonal spring bloom observed in this region. More front activities during the negative PDO and ENSO could be associated with Chl-a increase in this triangular area. Contrary to this mixing control scenario, a significant Chl-a increase (~36% increase) also developed during the positive PDO and ENSO modes after 2014 under conditions of higher SST, NHF, and weaker wind mixing following the stratification control scenario. This study used biologically relevant objective regionalization of a heterogeneous area to elucidate phytoplankton bloom dynamics and controls. Our analyses highlight the triangular area in the ECS for its region-specific linkages between Chl-a and multiple climate-sensitive environmental drivers, as well as the potential structural and functional variability in this region.

Submesoscale processes in the ocean vary rapidly in both space and time, and are often difficult to capture by field observations. Their dynamical connection with marine biology remains largely unknown because of the intrinsic link between temporal and spatial variations. In May 2015, satellite chlorophyll data demonstrated high concentration patches in the edge region between mesoscale eddies, which were higher than those in the cyclonic eddy core region in the northern South China Sea (NSCS). The underlying mechanisms were examined with a high-resolution physical-biological model. By tracking Lagrangian particles in the model, this study shows that the edge region between eddies is a submesoscale frontal region that is prone to intense upwelling and downwelling motions. We identified two key submesoscale mechanisms that affect nutrient transport flux significantly, submesoscale fontal dynamics and submesoscale coherent eddies. The dynamics associated with these two mechanisms were shown to be able to inject subsurface nutrients into the upper layer, generate the high chlorophyll patch, and alter phytoplankton community structure in the NSCS. This study shows the importance of submesoscale processes on phytoplankton dynamics in the NSCS and highlights the need for high-resolution observations.

Based on the optical properties of water constituents, the vertical variation of photosynthetically available radiation (PAR) can be well modeled with hyperspectral resolution; the intensive computing load, however, demands simplified modeling that can be easily embedded in marine physical and biogeochemical models. While the vertical PAR profile in homogeneous waters can now be accurately modeled with simple parameterization, it is still a big challenge to model the PAR profile in stratified waters with limited variables. In this study, based on empirical equations and simulations, we propose a dual-band model to characterize the vertical distribution of PAR using the chlorophyll concentration (Chl). With an inclusive dataset including cruise data collected in the Southeast Pacific and BGC-Argo data in the global ocean, the model was thoroughly evaluated for its general applicability in three aspects: 1) estimating the entire PAR profile from sea-surface PAR and the Chl profile, 2) estimating the euphotic layer depth from the Chl profile, and 3) estimating PAR just below the sea surface from in situ radiometry measurements. It is demonstrated that the proposed dual-band model is capable of generating similar estimates as that from a hyperspectral model, thus offering an effective module that can be incorporated in large-scale ecosystem and/or circulation models for efficient calculations.

Abstract Background The purpose of the study was to investigate whether pelvic incidence (PI) will affect the occurrence of PJK in Lenke 5 AIS patients after correction surgery and try to explore a better surgical scheme based on PI. Methods Lenke 5C AIS patients that underwent correction surgery with a minimum of a 2-year follow-up were identified. Demographic and radiographic data were collected preoperatively, postoperatively, and at the final follow-up. The comparison between the PJK and the Non-PJK group was conducted and the subgroup analysis was performed based on the preoperative value of PI to investigate the potential mechanism of PJK. Clinical assessments were performed using the Scoliosis Research Society (SRS)-22 questionnaire. Results The mean preoperative Cobb angle of the TL/L curve was 53.4°±8.6. At the final follow-up, the mean TL/L Cobb angle was drastically decreased to 7.3°±6.8 (P

Abstract Hepatocellular carcinoma (HCC) is one of the most common and most lethal malignant tumors in the world. Microvascular invasion (MVI) is a major risk factor for survival outcomes and intrahepatic metastasis after resection in patients with HCC. Relevant English literatures retrieved using PubMed on the research progress of MVI in patients with HCC were reviewed. For HCC patients, especially those with MVI, it is very important to develop a comprehensive and sequential treatment plan to support the long-term survival of patients. This manuscript reviewed and analyzed the risk factors for MVI; the preoperative prediction of MVI, which informs the selection of surgical strategies; and the current situation and future direction of comprehensive postoperative treatment strategies; to provide a basis for the comprehensive treatment of HCC patients with MVI. For HCC patients with MVI, the preoperative prediction of MVI may play a certain guiding role in planning procedures, and the comprehensive sequential postoperative pathological detection of HCC MVI may provide a basis for treatment decisions.

T7 peptide is considered as an antiangiogenic polypeptide. The presents study aimed to further detect the antiangiogenic mechanisms of T7 peptide and determine whether combining T7 peptide and meloxicam (COX-2/PGE2 specific inhibitor) could offer a better therapy to combat hepatocellular carcinoma (HCC). T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3β1 and αvβ3 pathways. Cell proliferation, migration, apoptosis, or tube formation ability were detected, and the expression of integrin-associated regulatory proteins was detected. The anti-tumor activity of T7 peptide, meloxicam, and their combination were evaluated in HCC tumor models established in mice. T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3β1 and αvβ3 pathways. Meloxicam enhanced the activity of T7 peptide under hypoxic condition. T7 peptide partly inhibited COX-2 expression via integrin α3β1 not αvβ3-dependent pathways under hypoxic condition. T7 peptide regulated apoptosis associated protein through MAPK-dependent and -independent pathways under hypoxic condition. The MAPK pathway was activated by the COX-2/PGE2 axis under hypoxic condition. The combination of T7 and meloxicam showed a stronger anti-tumor effect against HCC tumors in mice. The data highlight that meloxicam enhanced the antiangiogenic activity of T7 peptide in vitro and in vivo.

Maintaining an effective drug concentration in the nidus during the early stage is essential for the surgical treatment of osteoarticular tuberculosis (TB) and the prevention of internal infection. In this study, an implantable composite scaffold, denoted as n-HP@ICG, was synthesized by attaching isoniazid (INH) to chitosan followed by crosslinking via glutaraldehyde to porous nanohydroxyapatite/polyamide 66 (n-HA/PA66). Drug release and biocompatibility experiments showed that INH could be effectively released from the composite scaffold for approximately 15 days in vitro and 28 days in vivo with no obvious cytotoxicity or harm to liver or kidney function. The anti-TB test indicated that n-HP@ICG had satisfactory anti-TB effects, including the inhibition of Mycobacterium tuberculosis activity, proliferation and adhesion. The rabbit femoral condyle defect repair experiment showed that the composite scaffold had satisfactory osteoconduction and osseointegration. These results demonstrate that the n-HP@ICG composite scaffold can simultaneously provide relatively long-term drug release, biosafety, and anti-TB and bone regeneration activity and is thus promising for treating osteoarticular TB.

Background: Assessing the relation between arthritis and cognitive impairment could expand the understanding of health consequences of arthritis. The aim was to prospectively examine the association between arthritis and cognitive functions among middle-aged and elderly Chinese.Methods: Our analyses were based on data from the nationwide China Health and Retirement Longitudinal Study (2011–2016). Arthritis was ascertained by self-reported doctor diagnosis during the baseline survey. Cognitive functions were evaluated in three domains including episodic memory, mental status, and global cognition. Linear mixed models were employed to assess the association between baseline arthritis and cognition functions.Results: Of 7,529 Chinese adults, 49.79% were men, and mean age was 57.53 years. During a follow-up of 4 years, participants with baseline arthritis showed lower scores of episodic memory [β = −0.08; 95% confidence interval (CI): −0.14, −0.03], mental status (β = −0.14; 95% CI: −0.22, −0.05), and global cognition (β = −0.22; 95% CI: −0.34, −0.11), compared to those without arthritis. In addition, participants with arthritis showed increased rates of decline in mental status and global cognition by 0.04 (95% CI: 0.01, 0.08) and 0.05 (95% CI: 0.01, 0.09) units per year, respectively.Conclusion: Arthritis was associated with subsequent risk of poorer cognitive functions and slightly faster declines in cognitive functions among Chinese middle-aged and elderly adults. Our findings should be confirmed in future large prospective studies in Chinese and other populations.

The subarctic Pacific is one of the major high-nitrate, low-chlorophyll (HNLC) regions where marine productivity is greatly limited by the supply of iron (Fe) in the region. There is a distinct seasonal difference in the chlorophyll concentrations of the east and west sides of the subarctic Pacific because of the differences in their driving mechanisms. In the western subarctic Pacific, two chlorophyll concentration peaks occur: the peak in spring and early summer is dominated by diatoms, while the peak in late summer and autumn is dominated by small phytoplankton. In the eastern subarctic Pacific, a single chlorophyll concentration peak occurs in late summer, while small phytoplankton dominate throughout the year. In this study, two one-dimensional (1D) physical–biological models with Fe cycles were applied to Ocean Station K2 (Stn. K2) in the western subarctic Pacific and Ocean Station Papa (Stn. Papa) in the eastern subarctic Pacific. These models were used to study the role of Fe limitation in regulating the seasonal differences in phytoplankton populations by reproducing the seasonal variability in ocean properties in each region. The results were reasonably comparable with observational data, i.e., cruise and Biogeochemical-Argo data, showing that the difference in bioavailable Fe (BFe) between Stn. K2 and Stn. Papa played a dominant role in controlling the respective seasonal variabilities of diatom and small phytoplankton growth. At Stn. Papa, there was less BFe, and the Fe limitation of diatom growth was two times as strong as that at Stn. K2; however, the difference in the Fe limitation of small phytoplankton growth between these two regions was relatively small. At Stn. K2, the decrease in BFe during summer reduced the growth rate of diatoms, which led to a rapid reduction in diatom biomass. Simultaneously, the decrease in BFe had little impact on small phytoplankton growth, which helped maintain the relatively high small phytoplankton biomass until autumn. The experiments that stimulated a further increase in atmospheric Fe deposition also showed that the responses of phytoplankton primary production in the eastern subarctic Pacific were stronger than those in the western subarctic Pacific but contributed little to primary production, as the Fe limitation of phytoplankton growth was replaced by macronutrient limitation.

In addition to nutrients and light, temperature plays a crucial role in marine biogeochemical processes. In this study, the sensitivity of the growth rate of phytoplankton to temperature was systematically studied by using a two-level nested physical–biogeochemical coupled model for the Yangtze River estuary of the East China Sea. The physical component of the coupled model is configured from the Regional Ocean Modeling System (ROMS) with the highest horizontal resolution of 3 km. The biogeochemical component of the coupled model is based on the carbon, silicon and nitrogen ecosystem model (CoSiNE). Five specific growth rate of phytoplankton equations with different relation to temperature were tested with the objective of reproducing the temporal evolution of chlorophyll concentration as observed by SeaWiFS. Our results indicate that the specific growth rate of phytoplankton equation which is from Geider’s work, reaches a maximum at 22 °C and remains constant with higher temperature, can reproduce the seasonal variation of chlorophyll very well, and may be suitable for application in the physical–biogeochemical coupled model (ROMS-CoSiNE) of the Yangtze River estuary.

Marine biogeochemical models have been widely used to understand ecosystem dynamics and biogeochemical cycles. To resolve more processes, models typically increase in complexity, and require optimization of more parameters. Data assimilation is an essential tool for parameter optimization, which can reduce model uncertainty and improve model predictability. At present, model parameters are often adjusted using sporadic in-situ measurements or satellite-derived total chlorophyll-a concentration at sea surface. However, new ocean datasets and satellite products have become available, providing a unique opportunity to further constrain ecosystem models. Biogeochemical-Argo (BGC-Argo) floats are able to observe the ocean interior continuously and satellite phytoplankton functional type (PFT) data has the potential to optimize biogeochemical models with multiple phytoplankton species. In this study, we assess the value of assimilating BGC-Argo measurements and satellite-derived PFT data in a biogeochemical model in the northern South China Sea (SCS) by using a genetic algorithm. The assimilation of the satellite-derived PFT data was found to improve not only the modeled total chlorophyll-a concentration, but also the individual phytoplankton groups at surface. The improvement of simulated surface diatom provided a better representation of subsurface particulate organic carbon (POC). However, using satellite data alone did not improve vertical distributions of chlorophyll-a and POC. Instead, these distributions were improved by combining the satellite data with BGC-Argo data. As the dominant variability of phytoplankton in the northern SCS is at the seasonal timescale, we find that utilizing monthly-averaged BGC-Argo profiles provides an optimal fit between model outputs and measurements in the region, better than using high-frequency measurements.

ObjectiveTo build a model for proximal junctional kyphosis (PJK) prognostication in Lenke 5 adolescent idiopathic scoliosis (AIS) patients undergoing long posterior instrumentation and fusion surgery by machine learning and analyze the risk factors for PJK.Materials and MethodsIn total, 44 AIS patients (female/male: 34/10; PJK/non-PJK: 34/10) who met the inclusion criteria between January 2013 and December 2018 were retrospectively recruited from West China Hospital. Thirty-seven clinical and radiological features were acquired by two independent investigators. Univariate analyses between PJK and non-PJK groups were carried out. Twelve models were built by using four types of machine learning algorithms in conjunction with two oversampling methods [the synthetic minority technique (SMOTE) and random oversampling]. Area under the receiver operating characteristic curve (AUC) was used for model discrimination, and the clinical utility was evaluated by using F1 score and accuracy. The risk factors were simultaneously analyzed by a Cox regression and machine learning.ResultsStatistical differences between PJK and non-PJK groups were as follows: gender (p = 0.001), preoperative factors [thoracic kyphosis (p = 0.03), T1 slope angle (T1S, p = 0.078)], and postoperative factors [T1S (p = 0.097), proximal junctional angle (p = 0.003), upper instrumented vertebra (UIV) – UIV + 1 (p = 0.001)]. Random forest using SMOTE achieved the best prediction performance with AUC = 0.944, accuracy = 0.909, and F1 score = 0.667 on independent testing dataset. Cox model revealed that male gender and larger preoperative T1S were independent prognostic factors of PJK (odds ratio = 10.701 and 57.074, respectively). Gender was also at the first place in the importance ranking of the model with best performance.ConclusionThe random forest using SMOTE model has the great value for predicting the individual risk of developing PJK after long instrumentation and fusion surgery in Lenke 5 AIS patients. Moreover, the combination of the outcomes of a Cox model and the feature ranking extracted by machine learning is more valuable than any one alone, especially in the interpretation of risk factors.

Abstract Hepatocellular carcinoma (HCC) is a highly malignant disease with a poor prognosis and high mortality due to a low early diagnosis rate, resistance to systemic treatments and progression to late-stage liver disease. Owing to limitations in the detection of HCC and the lack of awareness of healthcare systems, fewer than 40% of HCC patients are eligible for surgery due to advanced stages of the disease at the time of diagnosis and the occurrence of multiple lesions in the cirrhotic or fibrotic liver. At present, the updated American Association for the Study of Liver Disease (AASLD) guidelines no longer recommend alpha-fetoprotein (AFP) testing as a part of diagnostic evaluation. Thus, it is imperative to establish a novel diagnostic strategy with high sensitivity and reliability to monitor risk factors to detect HCC at an early stage. In recent years, “liquid biopsy,” (including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)), has emerged as a technique for the characterization of circulating cells, providing a strong basis for the individualized treatment of patients. As a noninvasive detection method, liquid biopsy is expected to play an important role in the early diagnosis, dynamic monitoring of cancer patients and drug screening. In this review, we will focus on the clinical applications, recent studies and future prospects of liquid biopsy, particularly focusing on HCC.

Fourier ptychographic microscopy (FPM) is a newly developed imaging technique which stands out by virtue of its high-resolution and wide FOV. It improves a microscope’s imaging performance beyond the diffraction limit of the employed optical components by illuminating the sample with oblique waves of different incident angles, similar to the concept of synthetic aperture. We propose to use an objective lens with high-NA to generate oblique illuminating waves in FPM. We demonstrate utilizing an objective lens with higher NA to illuminate the sample leads to better resolution by simulations, in which a resolution of 0.28μm is achieved by using a high-NA illuminating objective lens (NA=1.49) and a low-NA collecting objective lens (NA=0.2) in coherent imaging (λ=488nm). We then deeply study FPM’s exact relevance of convergence speed to spatial spectrum overlap in frequency domain. The simulation results show that an overlap of about 60% is the optimal choice to acquire a high-quality recovery (520*520 pixels) with about 2 min’s computing time. In addition, we testify the robustness of the algorithm of FPM to additive noises and its suitability for phase objects, which further proves FPM’s potential application in biomedical imaging.

Cyclooxygenase (COX)-2 is overexpressed in many types of cancers including hepatocellular carcinoma (HCC). Meloxicam, a selective COX-2 inhibitor, has shown potential therapeutic effects against HCC, but the mechanisms accounting for its anti-cancer activities remain unclear.Meloxicam inhibited the ability of human HCC cells expressing higher levels of COX-2 to migrate, invade, adhere and form colonies through upregulating the expression of E-cadherin and downregulating the expression of matrix metalloproteinase (MMP) -2. Meloxicam induced cell apoptosis by upregulating pro-apoptotic proteins including Bax and Fas-L, and downregulating anti-apoptotic proteins including survivin and myeloid cell leukemia-1 (Mcl-1), through inhibiting phosphorylation of AKT. Addition of prostaglandin E2 (PGE2), the major product of COX-2, could abrogate the effects of meloxicam on the expression of survivin and myeloid cell leukemia-1 (Mcl-1), but not Bax and Fas-L, indicating that meloxicam induces cell apoptosis via both COX-2-dependent and -independent pathways. Meloxicam also induced cell autophagy by upregulating Beclin 1 and light chain 3-II. Specific inhibition of autophagy by 3-methyladenine and chloroquine had little effect on cell apoptosis but could enhance the pro-apoptotic effects of meloxicam by further upregulating the expression of Bax.Meloxicam executes its antitumor effects by targeting the COX-2/MMP-2/E-cadherin, AKT, apoptotic and autophagic pathways in COX-2-dependent and -independent pathways, and inhibition of cell autophagy could help to overcome the resistance to meloxicam-induced apoptosis in HCC.

Abstract Background The very low density lipoprotein receptor gene (VLDLR), a member of the low density lipoprotein receptor (LDLR) gene family, plays a crucial role in the synthesis of yolk protein precursors in oviparous species. Differential splicing of this gene has been reported in human, rabbit and rat. In chicken, studies showed that the VLDLR protein on the oocyte surface mediates the uptake of yolk protein precursors into growing oocytes. However, information on the VLDLR gene in duck is still scarce. Methods Full-length duck VLDLR cDNA was obtained by comparative cloning and rapid amplification of cDNA ends (RACE). Tissue expression patterns were analysed by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR). Association between the different genotypes and egg performance traits was investigated with the general linear model (GLM) procedure of the SAS® software package. Results In duck, two VLDLR transcripts were identified, one transcript (variant-a) containing an O-linked sugar domain and the other (variant-b) not containing this sugar domain. These transcripts share ~70 to 90% identity with their counterparts in other species. A phylogenetic tree based on amino acid sequences showed that duck VLDLR proteins were closely related with those of chicken and zebra finch. The two duck VLDLR transcripts are differentially expressed i.e. VLDLR-a is mainly expressed in muscle tissue and VLDLR-b in reproductive organs. We have localized the duck VLDLR gene on chromosome Z. An association analysis using two completely linked SNP sites (T/C at position 2025 bp of the ORF and G/A in intron 13) and records from two generations demonstrated that the duck VLDLR gene was significantly associated with egg production (P < 0.01), age of first egg (P < 0.01) and body weight of first egg (P < 0.05). Conclusions Duck and chicken VLDLR genes probably perform similar function in the development of growing oocytes and deposition of yolk lipoprotein. Therefore, VLDLR could be a candidate gene for duck egg performance and be used as a genetic marker to improve egg performance in ducks.