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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.

The magnetism of proteins and their contributions to magnetoreception and other magnetic bio-effects have been debated for decades, mostly focusing on the insufficient iron atoms and lacking physical explanations. Here we show that divalent metal cations alone, including Mg, Ca, and Zn cations, which are not traditional magnetic materials, can abruptly switch aromatic biomolecules from diamagnetic to exceptionally strongly paramagnetic. Remarkably, their paramagnetism is so strong, together with sequence-dependence, enabling the separation of DNA with different sequences under a moderate magnetic field, thus resulting in a DNA magnetophoresis prototype without any magnetic particle addition. Theoretical computations show that water helps stabilize the hydrated MgCl on the single aromatic ring via hydrated cation–π interactions, and the complex of the hydrated MgCl on the single aromatic ring possesses a magnetic moment of 1.0 μB, which induces the exceptionally strong paramagnetism of the biomolecules with cations. X-ray experiments demonstrate the novel electronic states of the cations adsorbed on aromatic rings, indicating the existence of magnetic moments in the complex. The finding reveals a new origin for the exceptionally strong paramagnetism and biological magnetism, provides new insights into the interactions between biological systems and magnetic fields, and will greatly benefit magnetically controlled applications and beyond.

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.

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.

Enamel non-cavitated lesions (NCLs) are subsurface enamel porosity from carious demineralization. The developed enamel cannot repair itself once NCLs occurs. The regeneration of mineral crystals in a biomimetic environment is an effective way to repair enamel subsurface defects. Previously, an amelogenin-derived peptide named QP5 was proven to repair demineralized enamel. In this work, inspired by amelogenesis, a novel biomimetic hydrogel composite containing the QP5 peptide and bioactive glass (BG) was designed, in which QP5 could promote enamel remineralization by guiding the calcium and phosphorus ions provided by BG. Also, BG could adjust the mineralization micro-environment to alkalinity, simulating the pH regulation of ameloblasts during enamel maturity. The BQ hydrogel composite showed biosafety and possessed capacity for enamel binding, ion release and pH buffering. Enamel NCLs treated with the BQ hydrogel composite showed a higher reduction in lesion depth and mineral loss both

The South China Sea (SCS) is the largest semi-enclosed marginal sea in the western Pacific. The alternation of East Asian monsoon causes a significant seasonal pattern of chlorophyll, primary productivity, and export flux of sinking particles. However, the source and sink of dissolved organic carbon (DOC) pools with different bioavailability are less studied. Here we evaluated the seasonal production of DOC in labile, semi-labile and refractory forms using a coupled physical-biogeochemical model. This study aims to understand the dynamics and budgets of organic matters in the SCS. Model results show that the production of labile, semi-labile and refractory DOC is highly correlated with the net primary productivity (NPP) which is higher in winter and lower in summer, reflecting a dependence of DOC on the NPP. The seasonal variation in Pearl River discharge dominates the DOC production in the northern coastal region. In the northeast, the Kuroshio intrusion associated frontal system is attributed to cause high winter production. The DOC production in the southwest is controlled by both winter mixing and summer upwelling. The production of refractory DOC with the least bioavailability favors carbon sequestration. Its annual mean production is 1.8±0.5 mg C m−2 d−1, equivalent to 26% of the export flux of particulate organic carbon at 1000 m.

Despite recent experiments and simulations suggesting that small-molecule inhibitors and some post-translational modifications (e.g., glycosylation and ubiquitination) can suppress the pathogenic aggregation of proteins due to steric hindrance, the effect of steric hindrance on amyloid formation has not been systematically studied. Based on Monte Carlo simulations using a coarse-grained model for amyloidogenic proteins and a hard sphere acting as steric hindrance, we investigated how steric hindrance on proteins could affect amyloid formation, particularly two steps of primary nucleation, namely, oligomerization and conformational conversion into a β-sheet-enriched nucleus. We found that steric spheres played an inhibitory role in oligomerization with the effect proportional to the sphere radius

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.

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.

Understanding the influence of fine atmospheric particles (PM2.5) on cellular biophysical properties is an integral part for comprehending the mechanisms underlying PM2.5-induced diseases because they are closely related to the behaviors and functions of cells. However, hitherto little work has been done in this area. In the present work, we aimed to interrogate the influence of the PM2.5 water-soluble compound (PM2.5-WSC) on the biophysical performance of a human lung carcinoma epithelial cell line (A549) by exploring the cellular morphological and mechanical changes using atomic force microscopy (AFM)-based imaging and nanomechanics. AFM imaging showed that PM2.5-WSC treated cells exhibited evidently reduced lamellipodia and an increased height when compared to the control group. AFM nanomechanical measurements indicated that the treated cells had higher elastic energy and lower adhesion work than the control group. Our western blot assay and transmission electron microscopy (TEM) results revealed that after PM2.5-WSC treatment, the contents of cytoskeletal components (β-actin and β-tubulin) increased, but the abundance of cell surface microvilli decreased. The biophysical changes of PM2.5-WSC-treated cells measured by AFM can be well correlated to the alterations of the cytoskeleton and surface microvilli identified by the western blot assay and TEM imaging. The above findings confirm that the adverse risks of PM2.5 on cells can be reliably assessed biophysically by characterizing the cellular morphology and nanomechanics. The demonstrated technique can be used to diminish the gap of our understanding between PM2.5 and its harmful effects on cellular functions.

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 2 = 0.425, P = 0.514). For low PI patients, there is no significant difference where the UIV is located with regards to the TK apex between the PJK and Non-PJK subgroups (χ2 = 1.103, P = 0.401). For high PI patients, PJK was more likely to occur when UIV was cephalad to than caudal to the TK apex (31.25 % vs. 4.7 %, P = 0.038). There was no significant difference in the selection of LIV between the two groups. Conclusions There is no difference in the incidence of PJK between the Lenke 5 AIS patients with low PI (< 45°) and high PI (≥45°), but the main risk factor of PJK should be different. For patients with low PI, overcorrection of LL should be strictly avoided during surgery. For patients with high PI, the selection of UIV should not be at or cephalad to the apex of thoracic kyphosis to retain more mobile thoracic segments.

BACKGROUND CONTEXT Tranexamic acid (TXA) is widely used in surgery for adolescent idiopathic scoliosis (AIS) and has been proved to be efficacious in reducing intraoperative blood loss (IBL) and the transfusion rate. However, the routine TXA regimen was intraoperative administration alone, in which the concentration of TXA could not cover the whole process of hyperfibrinolysis. And, its ability to control the massive postoperative blood loss (PBL) may be insufficient. Thus, we promoted a multiple-dose regimen of TXA for patients with AIS who underwent surgical correction. PURPOSE The primary aims were (1) to determine whether the multiple-dose regimen of TXA could reduce PBL and the postoperative transfusion rate, and (2) to compare the efficacy of oral administration with intravenous administration. The secondary aims were (3) to evaluate whether this regimen could alleviate inflammatory response, and (4) to assess the occurrence of drug-related side effects. STUDY DESIGN Prospective, double-blinded, randomized controlled trial. PATIENT SAMPLE A total of 108 patients with AIS who underwent posterior scoliosis correction and spinal fusion (PSS) were enrolled in this study. OUTCOME MEASURES The primary parameters were PBL and postoperative transfusion rate. Other parameters such as total blood loss (TBL), maximum hemoglobin (Hb) decrease, volume of drainage, inflammation markers (interleukin-6 [IL-6] and C-reactive protein [CRP]), and occurrence of complications were also collected and compared. Multiple regression analysis was used to examine the variables that affected PBL. METHODS Patients were randomized into three groups. All patients received intravenous TXA 50 mg/kg loading dose and 10 mg/kg/h maintenance dose during surgery. Group A received 1 g oral TXA at 4 hours, 10 hours, and 16 hours postoperatively; group B received 0.5 g intravenous TXA at 6 hours, 12 hours, and 18 hours postoperatively; group C received placebo. RESULTS The mean PBL and postoperative transfusion rate in group A (957.8±378.9 mL, 13.89%) and B (980.3±491.8 mL, 11.11%) were significantly lower than those in group C [1,495.9±449.6 mL, mean differences=538.1 mL, 95% confidence interval (CI), 290.1-786.1 mL, p

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.

Titanium mini-plate has been used in unilateral open-door laminoplasty to maintain the open angle of laminae. Previously, both all-level fixation (C3-C7) and alternative-level (C3, C5, C7) unilateral open-door laminoplasty have been proven to have satisfactory clinical outcomes. However, whether they could achieve similar long-term clinical and radiographic efficacy is still questionable.To compare the long-term clinical and radiological outcomes between alternative-level and all-level fixation unilateral open-door laminoplasty with a mini-plate fixation system.Retrospective comparative study.Ninety-one patients who underwent unilateral open-door laminoplasty.Clinical results including Japanese Orthopedic Association score, Visual Analogue Score, Neck Dysfunction Index score. Radiographic results including cervical curvature index, cervical range of motion, and the spinal canal expansive parameters, including anteroposterior diameter, Pavlov's ratio, and open angle.Between April 2007 and June 2011, 91 patients with minimum 7-year postoperative follow-up were included. Thirty-eight underwent alternative-level fixation (group A) and 53 underwent all-level fixation (group B). Demographic data, including age, gender, operative time, blood loss, and cost, were collected and compared between the two groups. Clinical and radiographic data were obtained preoperatively, at 3 and 6 months and 1 and 3 years postoperatively, as well as at final follow-up. The difference between the two groups and between different time points within one group was compared.Both groups obtained satisfactory clinical outcomes till the final follow-up. No statistic difference was found in Japanese Orthopedic Association, Visual Analogue Score, and Neck Dysfunction Index between the two groups throughout the whole follow-up. Both groups maintained APD and Pavlov's ratio well till follow-up. However, statistic difference was found in the open angle between two groups at final follow-up (34.17±2.75° vs. 36.19±1.80°, p.05). When we subdivided the cervical segments in group A, we found the mini-plate segments showed maintenance in open angle but a 4.52° decrease in suture segments. The mean cost in group B (17,669.82±1,157.65 $) was significantly higher than in group A (11,452.19±871.07 $; p.05).Despite a difference in the maintenance of open angle, both fixation methods achieved satisfactory clinical outcomes. We believe alternative-level fixation is also a safe, effective, and economical fixation method.

The northern South China Sea (NSCS) is a dynamically complex region whose shelf and slope currents are driven by different mechanisms. In this study, we used field measurements to identify clear interannual variations in the circulation related to the El Nino-Southern Oscillation cycle. To investigate the modulation mechanisms, we used a high-resolution numerical model that covers the shelf and slope regions of the NSCS. The results indicate that the stronger southwestward slope current during La Nina and stronger northeastward shelf current during El Nino in summer and winter are largely related to changes in wind forcing. The Kuroshio intrusion into the NSCS does not appear to significantly affect the circulation in the southwestern shelf region.

Background The optimal management of lumbar synovial cysts (LSCs) has always been controversial. Open or minimally invasive partial hemilaminotomy as a direct decompression approach has been widely studied, whereas to our knowledge, there has been no report of an indirect decompression method for LSC. Case Description A 60-year-old male complained of chronic low back pain for 2 years. He reported that the pain had been getting worse and started radiating to the bilateral posterior thighs and right lateral calf for 6 months. An ovoid lesion with a hyperintense center attached to the medial side of the right facet joint at the L4-5 level, as well as L4-5 dynamic instability, were found with magnetic resonance imaging and lumbar x-ray examinations, respectively. L4-5 oblique lumbar interbody fusion combined with anterior fixation was performed. After surgery, the patient felt distinct pain relief and was discharged on the third day postoperatively. Three months later, lumbar magnetic resonance imaging and 3-dimensional computed tomography were performed again. The L4-5 disk height and foraminal height recovered from 7.1–12.3 mm and 14.8–18.5 mm, respectively. No evidence of a cyst was disclosed. The patient did not complain of any low back pain or radicular pain during the 12-month follow-up. Conclusions Indirect decompression surgery may be a new option for the management of LSC, especially in those with lumbar instability and that communicate with the facet joint. Further research with a larger and more comprehensive sample population is required.

Nanoparticles (NPs) enter a cell primarily via endocytosis, during which they are engulfed by the cell and reside in lipid vesicles named endosomes. Apart from when an endosome is pinched off the plasma membrane, structural integrity of its lipid membrane is usually well maintained. Under certain circumstances, however, such structural integrity can be considerably perturbed by a nanoparticle. For instance, recent experiments [Chu et al., Sci. Rep., 2014, 4, 4495] indicate that nanodiamonds with sharp corners can escape from an endosome by piercing its lipid membrane. Nonetheless, the energetics of this behavior and how it may be controlled by membrane adhesion and NP morphology remain unclear. In this work, we employ continuum modeling to investigate membrane pore formation induced by the spontaneous binding of a sharp nanoparticle. Based on two axial-symmetric NP models, we characterize the indispensable role played by curvature heterogeneity, membrane adhesion, and the sharpness as well as the size of a nanoparticle in 'breaking' a lipid membrane. Apart from revealing a general mechanism of NP binding-induced membrane pore formation, our results provide the reference for improving the endosomal escape of nanoparticles through manipulating their morphology, a direction that can be explored either independently or combined with existing strategies targeting NP surface chemistry.

Typhoons pose great threats to coastal regions, leaving distinctive ocean surface changes along the typhoon track before landing. However, a quantitative description of the spatial and temporal patterns of typhoon-induced oceanic responses remains unclear. Sixteen years of composited data of sea surface temperature (SST) and sea surface chlorophyll-a (Chl-a) in the South China Sea demonstrate that typhoon-induced changes initiate immediately before the arrival of the typhoon and continue to increase during its passage. The largest decrease in temperature occurred one day after the typhoon, leading the maximum Chl-a increase by four days. The spatial distribution of changes in SST and Chl-a clearly shows the prominent enhancement to the right of the typhoon's path. Both typhoon features and ocean status determine the corresponding impact on the oceans, as large temperature responses are associated with strong wind, slow translation speed and shallow mixed layer depth (MLD). The Chl-a responses generally followed the same rule, but the maximum Chl-a increase was found with a moderate value of the MLD that was most favorable to induce phytoplankton blooms. Quantifying the typhoon footprints will help to predict how the ocean responds to extreme events in the future climate.

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.

Aims To prospectively examine the association between arthritis and type 2 diabetes (T2D) in the Chinese population and confirm this association through a comprehensive meta-analysis of cohort studies. Meterials and methods Data were from the China Health and Retirement Longitudinal Study which was started in 2011-2013 and followed up in 2013-2014 and 2015-2016. Arthritis was defined as self-reported physician diagnosis at baseline, and incident T2D was determined by self-reported physician diagnosis, fasting blood glucose ≥7.0 mmol/L or glycosylated haemoglobin ≥6.5% during the follow-ups. Cox proportional hazards regression models were used to assess the association between arthritis and risk for T2D. A meta-analysis was conducted to pool our effect estimate and those from other cohort studies using a random-effects model. Results Eleven thousand four hundred and eight participants (47.9% men; mean age: 59.3 years) were included in final analyses. During a 4-year follow-up, 981 participants reported incident T2D. Compared with individuals without arthritis, those with arthritis at baseline had an 18% higher risk for incident T2D (multivariable-adjusted hazard ratio: 1.18; 95% confidence interval: 1.04, 1.34). In the meta-analysis of 13 cohort studies including ours, a total of 2,473,514 participants were included with 121,851 incident diabetes. The pooling HR was 1.32 (95% CI: 1.21, 1.44) for the association between arthritis and diabetes. Conclusion Arthritis was associated with an increased risk of incident diabetes in Chinese adults, and the positive association was confirmed in the meta-analysis of cohort studies. Our work can inform clinical trials to assess the effectiveness of arthritis treatments in reducing risk of diabetes.

The South China Sea (SCS) is strongly influenced by the East Asian monsoon system with seasonal reversal. Measurements from a 7-year continuous sediment trap located in the central SCS showed a clear seasonal pattern. The particulate organic carbon (POC) export flux at the depth of 1200 m was considerably higher in monsoon seasons. The driving dynamics leading to this seasonal variability of POC export, however, remains inadequately understood. Here, a one-dimensional physical-biogeochemical coupled model was developed to simulate the temporal variability of a lower-trophic planktonic ecosystem. The modeled POC export flux compared reasonably well with the 7-year time series from moored sediment trap. Model results showed that the POC export flux at 1200 m is highly correlated with the 0–100 m integrated primary productivity and with the export flux at 100 m, implying that the seasonal variability of sediment trap data could be induced by changes in phytoplankton production and its vertical export. Further model analysis suggested that the annual mean export ratio (e-ratio) at 100 m and transfer efficiency at 1200 m in the central SCS were 0.19 and 0.07, respectively, which are lower than those in high latitudes. The winter monsoon favors not only surface carbon fixation but also export to the deep ocean. The heat flux is the dominant factor regulating the seasonal cycle of mixed layer depth, nutrient supply, and the growth of phytoplankton in this region. The wind-driven mixing can further facilitate upward nutrient transport to the surface and amplify the seasonal amplitude of the POC export flux.

Background Litter size affects fetal development but its relation to diet-induced fatty liver later in life is unknown. Objectives This aim of this study was to test the hypothesis that litter size influences postweaning fatty liver development in response to soybean oil-supplemented diet. Methods Weanling twin (TW) or triplet (TP) male lambs (n = 16) were fed a control diet or 2% soybean oil-supplemented diet (SO) for 90 d. Liver tissue morphology, biochemical parameters, and lipid metabolic enzymes were determined. Hepatic gene expression was analyzed by RNA sequencing (n = 3), followed by enrichment analysis according to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed genes involved in lipid metabolism were further verified by quantitative reverse transcriptase-polymerase chain reaction (n = 4). All data were analyzed by a 2-factor ANOVA, apart from differentially expressed genes, which were identified by the Benjamini-Hochberg approach (q value ≤0.05). Results SO increased liver triglyceride (by 55%) and nonesterified fatty acid (by 54%) concentrations in TPs (P ≤ 0.05) but not in TWs (P > 0.05). SO also induced a 2.3- and 2.1-fold increase in the liver steatosis score of TPs and TWs, respectively (P ≤ 0.05). Moreover, SO reduced the activity of lipolytic enzymes including hepatic lipase and total lipase in TPs by 47% and 25%, respectively (P ≤ 0.05). In contrast, activities of lipogenic enzymes, including malic enzyme and acetyl coenzyme A carboxylase, were significantly higher in TPs (P ≤ 0.05). Moreover, TPs had higher expression of lipogenic genes, such as FASN (by 45%) and APOB (by 72%), and lower expression of lipolytic genes, such as PRKAA2 (by 28%) and CPT1A (by 43%), compared with TWs (P ≤ 0.05). Conclusions TPs have a gene expression profile that is more susceptible to SO-induced fatty liver than that of TWs, which indicates that insufficient maternal nutrient supply at fetal and neonatal stages may increase the risk of nonalcoholic fatty liver disease.

Satellite chlorophyll a (Chl) is an essential parameter for large-scale studies on changes in the marine ecosystem and biogeochemistry. However, in the eastern China seas (ECSs), the coexistence and interaction of turbid and clear water pose challenges to the application of standard satellite Chl products to studies on phytoplankton dynamics. Based on the empirical modification of the OC-CCI (Ocean Colour Climate Change Initiative) standard products, we herein provide a locally modified chlorophyll a (LMC) dataset and compare the large-scale Chl distributions with satellite and in-situ Chl datasets. Compared with standard Chl, LMC has a higher correlation with in-situ data (R2 = 0.58) and lower Bias (0.08) and is more consistent with the ship-measured Chl distributions. Using the LMC dataset, we analyzed the climatological Chl distributions in the ECSs and classified the Chl annual cycles into four types. Our results suggest that high Chl patterns not only rely on nutrient supply, but also relate to light conditions controlled by vertical mixing and suspended matter. The different Chl annual cycles are mainly caused by differences in the duration and range of nutrients and light limitation, and thus their distributions tend to vary with water depth. We believe that this work presents a more accurate dataset in the ECSs and can improve the understanding of local biogeochemical cycles.

The East China Sea (ECS) is one of the largest marginal seas in the Northwest Pacific, and also one of the most productive regions of the global ocean. Using a three-dimensional Pacific physical-biological model, we investigate the interannual variation of phosphate transport via Kuroshio intrusion (KIPT) in the eastern boundary of the East China Sea (ECS) and its influence on the ECS biological process during 1997 to 2016. The KIPT into the ECS mainly occurs in the northeast of Taiwan and southwest of Kyushu, with stronger interannual variability in the northeast of Taiwan. The variation of the KIPT is more significant in the near-bottom water, and is dominated by volume transport. On the interannual timescale, the KIPT changes in response to the shift of the Kuroshio axis and to the bottom upwelling in the ECS eastern boundary. When the Kuroshio axis is closer to (farther away from) the ECS shelf, the strength of the bottom upwelling increases (decreases). This process induces more (less) significant topographic beta spiral, which causes an anticyclonic (cyclonic) eddy-like bottom velocity feature in the northeast of Taiwan. Eventually, more phosphate is transported to the ECS inner shelf, which increases chlorophyll concentration around the Zhoushan Islands and Yangtze Estuary but reduces chlorophyll concentration in the ECS outer shelf. Conversely, the chlorophyll increases in the ECS outer shelf but decreases around the Zhoushan Islands and Yangtze Estuary when there is less phosphate transport. This study highlights the importance of Kuroshio intrusion in connecting the inner and outer shelves of the ECS on the interannual timescale. Phosphate transport into the East China Sea via Kuroshio intrusion shows great interannual variability in the northeast of Taiwan. On the interannual timescale, the variation of phosphate transport into the East China Sea via Kuroshio intrusion is dominated by volume transport. When the Kuroshio axis is closer to the East China Sea shelf, there is more phosphate transport into the East China Sea, and chlorophyll increases around the Zhoushan Islands and Yangtze Estuary.

Background Spinal tuberculosis accounts for more than 50% of bone tuberculosis cases. This study compared clinical, radiological and functional outcomes between anterior and posterior approaches for treatment of middle or lower thoracic spinal tuberculosis in elderly patients. Methods We retrospectively examined middle or lower thoracic spinal tuberculosis (T5–T12) in patients over 65 years. All procedures included debridement, decompression, autologous bone graft and fixation. Surgical procedure, surgical duration, estimated blood loss during surgery and laboratory results were recorded. Pleural effusion volume, thoracic cavity volume, Oswestry Disability Index score, neurological status, radiological parameters and complication rate were evaluated. Results No significant difference was found in surgical duration, blood loss, kyphosis angle correction, loss of correction, thoracic cavity volume, or complication rate between the two groups (P > 0.05). Average postoperative pleural effusion volumes were 605.9 ± 209.5 mL (377–1074 mL) and 262.9 ± 228.1 mL (0–702.4 mL) in the anterior and posterior groups, respectively (P = 0.004). Average hospitalization durations were 26.4 ± 10.5 days (17–53 days) and 19.2 ± 5.0 days (14–30 days) (P = 0.04). Average postoperative serum albumin levels were 24.19 ± 3.84 g/L (19–29.5 g/L) and 28.24 ± 2.52 g/L (24.4–31.6 g/L) (P = 0.01). No relapse or reinfection was observed in either group at the final follow-up. Surgical revision was not required in either group. Conclusions Both anterior and posterior surgeries can be used to treat middle or lower thoracic spinal (T5-T12) tuberculosis in elderly patients. In general, the posterior approach might be superior, especially for patients with poor general health.

3577 Background: Dual blockade of immune checkpoint and angiogenesis is an effective strategy for multiple cancers. We initiated an open-label, multicenter phase II basket study to evaluate the antitumor activity and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (a receptor tyrosine kinase inhibitor) in patients (pts) with advanced solid tumors. Herein, we report the results from the metastatic colorectal cancer (mCRC) cohort. Methods: Pts with histologically confirmed mCRC, who had received previous irinotecan, oxaliplatin, and fluoropyrimidine combination chemotherapy, and progressed after ≥ 2 lines of systemic treatment were enrolled to receive camrelizumab (200 mg i.v. every 3 weeks) and famitinib (20 mg orally once daily). Primary endpoint was objective response rate (ORR) per RECIST version 1.1. Results: Between Jul 10, 2020, and Jul 12, 2021, of all the 44 mCRC pts enrolled, 14 (31.8%) pts had colon cancer (CC) and 30 (68.2%) pts had rectal cancer (RC). As of Nov 30, 2021, the median time from enrollment to data cutoff was 10.6 months (range, 4.7-16.7). The ORR was 13.6% (95% CI, 5.2-27.4) and the DCR was 45.5% (95% CI, 30.4-61.2) in all mCRC pts. Of them, no pts with CC achieved response; six pts with RC achieved PR, with the ORR of 20.0% (95% CI, 7.7-38.6) and the DCR of 46.7% (95% CI, 28.3-65.7). Pts with RC showed a median duration of response (DoR) of 7.1 months (95% CI, 2.3-not reached [NR]). The median overall survival (OS) was 15.2 months (95% CI, 7.2-NR) in pts with RC. Of all 44 mCRC pts, 28 (63.6%) had grade 3 or higher treatment related adverse events (TRAEs), mainly hypertension (25.0%), proteinuria (18.2%), decreased platelet count (11.4%), decreased neutrophil count (11.4%) and palmar-plantar erythrodysaesthesia syndrome (11.4%). Three (6.8%) pts discontinued any study treatment due to TRAEs. No grade 5 TRAE was reported. Conclusions: Camrelizumab plus famitinib appeared to show encouraging antitumor activity in pts with mCRC, especially in those with RC, and the safety profile of this combination regimen seemed to be manageable and consistent with single agent alone. Clinical trial information: NCT04346381. [Table: see text]

OBJECTIVE: To investigate the relationship between O-EA angle and lower cervical curvature in patients with anterior atlantoaxial dislocation undergoing occipitocervical fusion, and to analyze the effect of O-EA angle on lower cervical curvature. METHODS: The clinical data of 61 patients with anterior atlantoaxial dislocation undergoing occipitocervical fusion who were admitted between April 2010 and July 2018 and met the selection criteria were retrospectively analyzed. There were 32 males and 29 females, with an age of 14-76 years (mean, 50.7 years). The fixed segment included 19 cases of C(0)-C(2), 27 cases of C(0)-C(3), 14 cases of C(0)-C(4), and 1 case of C(0)-C(5). The O-EA angle, C(2-7) Cobb angle, and T(1) tilt angle were measured before operation and at last follow-up. According to the O-EA angle measured at last follow-up, the patients were divided into 105° group (group C), and compared the differences of gender, age, fixed segment (short segment was at C (3) and above, long segment was beyond C(3)), and C(2-7) Cobb angle. Correlation analysis between the O-EA angle and C(2-7) Cobb angle before operation and at last follow-up, as well as the changes of O-EA angle and C(2-7) Cobb angle between before operation and at last follow-up were analyzed. RESULTS: All 61 patients were followed up 12-24 months, with an average of 22.4 months. There was no significant difference in O-EA angle, C(2-7) Cobb angle, and T(1) tilt angle before operation and at last follow-up (P>0.05). According to the last follow-up O-EA angle grouping, there were 14 cases in group A, 29 cases in group B, and 18 cases in group C. There was no significant difference in age, gender composition, and fixed segment composition among the three groups (P>0.05); the differences in C(2-7) Cobb angles among the three groups were significant (P

Understanding the influence of fine atmospheric particles (PM

Study Design Comparative study Objective To compare manual and deep learning-based automated measurement of Cobb angle in adolescent idiopathic scoliosis. Methods We proposed a fully automated framework to measure the Cobb angle of AIS patients. Whole-spine images of 500 AIS individuals were collected. 200 digital radiographic (DR) images were labeled manually as training set, and the remaining 300 images were used to validate by mean absolute error (MAE), Pearson or spearman correlation coefficients, and intra/interclass correlation coefficients (ICCs). The relationship between accuracy of vertebral boundary identification and the subjective image quality score was evaluated. Results The PT, MT, and TL/L Cobb angles were measured by the automated framework within 300 milliseconds. Remarkable 2.92° MAE, .967 ICC, and high correlation coefficient (r = .972) were obtained for the major curve. The MAEs of PT, MT, and TL/L were 3.04°, 2.72°, and 2.53°, respectively. The ICCs of these 3 curves were .936, .977, and .964, respectively. 88.7% (266/300) of cases had a difference range of ±5°, with 84.3% (253/300) for PT, 89.7% (269/300) for MT, and 93.0% (279/300) for TL/L. The decreased bone/soft tissue contrast (2.94 vs 3.26; P=.039) and bone sharpness (2.97 vs 3.35; P=.029) were identified in the images with MAE exceeding 5°. Conclusion The fully automated framework not only identifies the vertebral boundaries, vertebral sequences, the upper/lower end vertebras and apical vertebra, but also calculates the Cobb angle of PT, MT, and TL/L curves sequentially. The framework would shed new light on the assessment of AIS curvature.

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.

The appropriate translocation speed of a single-stranded DNA (ssDNA) through a solid-state nanopore is crucial for DNA sequencing technologies. By studying the geometry effect of graphene-MoS

Objective To 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 methods In 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. Results Statistical 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. Conclusion The 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.

Toxic abnormal aggregation of α-synuclein (α-Syn) is a feature of Parkinson’s disease. Several biochemical and biophysical studies have demonstrated that many post-translational modifications (PTM) of α-Syn could distinctly alleviate its oligomerization-mediated toxicity. Recently, a compelling link is emerging between the PTM O-GlcNAcylation (O-GlcNAc) and protein aggregation, yet the underlying molecular mechanism remains unclear. Based on the all-atom molecular dynamics simulations, we found that O-GlcNAc modifications can suppress the process of oligomerization of α-Syn aggregates via a steric effect—the additional O-linked glycosyl group disrupts the formation of hydrogen bonds (H-bonds) between α-Syn monomers. Besides, we proposed a theoretical model to further capture the physical mechanism of α-Syn aggregation/disaggregation in the absence/presence of O-GlcNAc-modified α-Syn. Our findings unveil the molecular mechanism of the O-GlcNAc-induced inhibition of α-Syn oligomerization, which may help to understand how O-GlcNAc prevents the oligomerization of other proteins and provides the guideline for the development of O-GlcNAc-based therapeutic strategies in neurodegenerative diseases.