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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.

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.

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.

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.

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.

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.

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.

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.

3D-printed titanium alloy orthopedic implants combine the dual advantages of 3D printing and titanium alloys implants, which not only have complex structures that cannot be manufactured by traditional techniques, but also inherit the excellent physical and chemical properties of titanium and its alloys, so they are widely used in the field of orthopedics in recent years. The inherent porous structure of 3D-printed implants and the original modification processes of titanium alloys provide the conditions for the functionalization of implants. To meet the needs of orthopedic surgeons and patients, functionalized implants with the ability of long-term stability promotion, anti-infection or anti-tumor have been developed, in which various methods of functionalization deserve to be summarized, compared and analyzed. Therefore, in this review, we will collect the existing knowledge on functionalization of 3D-printed titanium alloy orthopedic implants and give our own opinion.

Hepatocellular carcinoma (HCC) is regarded as a leading cause of cancer-related deaths, and its progression is associated with hypoxia and the induction of hypoxia-inducible factor (HIF). Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, induces cell death in various malignancies. However, the underlying mechanism remains to be elucidated in HCC, especially under hypoxic conditions. The alteration of COX-2 and HIF-1α oncogenicity was evaluated in HCC specimens by tissue microarray. Cell viability, angiogenesis assays, and xenografted nude mice were used to evaluate the effects of meloxicam, along with flow cytometry to detect the cell cycle, apoptosis, and mitochondrial membrane potential (ΔΨm) of HCC. qRT-PCR, Western blotting, immunofluorescence, immunohistochemistry, luciferase assay, and RNAi were carried out to determine the HIF-1α signaling affected by meloxicam. In this study, we showed that meloxicam exerts antiproliferative and antiangiogenesis efficacy in vitro and in vivo and causes disruption of mitochondrial membrane potential (ΔΨm), thus leading to caspase-dependent apoptosis under hypoxic environments. Exposure to meloxicam significantly reduced HIF-1α transcriptional activation and expression through sequestering it in the cytoplasm and accelerating degradation via increasing the von Hippel-Lindau tumor suppressor protein (pVHL) in HCC. These data demonstrated that inhibition of HIF-1α by meloxicam could suppress angiogenesis and enhance apoptosis of HCC cells. This discovery highlights that COX-2 specific inhibitors may be a promising therapy in the treatment of HCC.

MAO-treated porous Ti6Al4V holds enormous potential for use in orthopedic implants due to their excellent biocompatibility and favourable mechanical strength. However, the effects on the V ion accumulation and release following the MAO-treated Ti6Al4V remain undetermined. The aim of the present study was to assess the effects of Vanadium on biocompatibility. In this study, the surface features and chemical compositions were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectrometry (EDS) and X-ray photoelectron spectroscopy (XPS). The ion release of Ti, Al and V was quantitatively measured by inductively-coupled plasma mass spectroscopy (ICP-MS) after immersion in Hanks' solution. To probe the mechanism of V release, the corrosion resistance of porous Ti6Al4V before and after the MAO process was evaluated by electrochemical tests. Thereafter, the effects on the biocompatibility were tested in vitro by cell culture assays and then in vivo by subcutaneous embedment. Finally, the bone tissue response and in vivo release profile of V ions were characterized by intra-osseous implantation. Therefore, this study suggests that the effect of V released from MAO-treated porous Ti6Al4V on biocompatibility and application safety is small and preventable.

Total internal reflection fluorescence microscopy (TIRFM) provides high optical sectioning capability and superb signal-to-noise ratio for imaging of cell cortex structures. The development of multi-angle (MA)-TIRFM permits high axial resolution imaging and reconstruction of cellular structures near the cell surface. Cytoskeleton is composed of a network of filaments, which are important for maintenance of cell function. The high-resolution imaging and quantitative analysis of filament organization would contribute to our understanding of cytoskeleton regulation in cell. Here, we used a custom-developed MA-TIRFM setup, together with stochastic photobleaching and single molecule localization method, to enhance the lateral resolution of TIRFM imaging to about 100 nm. In addition, we proposed novel methods to perform filament segmentation and 3D reconstruction from MA-TIRFM images. Furthermore, we applied these methods to study the 3D localization of cortical actin and microtubule structures in U373 cancer cells. Our results showed that cortical actins localize ∼ 27 nm closer to the plasma membrane when compared with microtubules. We found that treatment of cells with chemotherapy drugs nocodazole and cytochalasin B disassembles cytoskeletal network and induces the reorganization of filaments towards the cell periphery. In summary, this study provides feasible approaches for 3D imaging and analyzing cell surface distribution of cytoskeletal network. Our established microscopy platform and image analysis toolkits would facilitate the study of cytoskeletal network in cells.

Temporal evolution of near-surface chlorophyll (CHL) associated with mesoscale eddies over entire eddy lifespan is complicated. Based on satellite measurements and a reanalysis data set, we identify and quantify major temporal and spatial CHL responses in cyclonic eddies in the southeastern Pacific, and explore the associated mechanisms. Only few temporal CHL variations can be directly linked to the four primary mechanisms: “eddy pumping,” “eddy trapping,” “eddy stirring,” and “eddy-induced Ekman pumping.” About 80% of the temporal CHL variations are too complex to be explained by a single mechanism. Five characteristic CHL responses, including classic dipoles (CD), positive-dominant dipoles (PD), negative-dominant dipoles (ND), positive monopoles (PM), and negative monopoles (NM) are identified using the self-organizing map (SOM). CD, a dominant response induced primarily by “eddy stirring,” has a continued increasing of frequency of occurrence with time, although its contribution to the total CHL variability remains low. As the secondary prominent response, NM has two peaks of frequency of occurrence at eddy formation and maturation stages, mainly accounted by “eddy trapping” after eddy breakup and “eddy-induced Ekman pumping,” respectively. The sum of frequency of occurrence of PD and PM are comparable to that of NM. The initial positive CHL at eddy formation stage is associated with “eddy trapping.” The significant positive CHL increase from the eddy intensification to early decay stage is mainly attributed to “eddy pumping.” Although the frequency of occurrence of ND is the smallest, its contribution to negative CHL anomalies is unnegligible.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. The Yes-associated protein-1 (YAP) plays a critical role in cell proliferation, apoptosis and angiogenesis. Verteporfin is a photosensitizer used in photodynamic therapy and also a small molecular inhibitor of the Hippo-YAP pathway. However, little is known about whether verteporfin could inhibit YAP activity in PDAC cells. Our present results showed that verteporfin suppressed the proliferation of human PDAC PANC-1 and SW1990 cells by arresting cells at the G1 phase, and inducing apoptosis in dose- and time-dependent manners. Verteporfin also inhibited the tumor growth on the PDAC xenograft model. Treatment with verteporfin led to downregulation of cyclinD1 and cyclinE1, modulation of Bcl-2 family proteins and activation of PARP. In addition, verteporfin exhibited an inhibitory effect on angiogenesis and vasculogenic mimicry via suppressing Ang2, MMP2, VE-cadherin, and α-SMA expression in vitro and in vivo. Mechanism studies demonstrated that verteporfin impaired YAP and TEAD interaction to suppress the expression of targeted genes. Our results provide a foundation for repurposing verteporfin as a promising anti-tumor drug in the treatment of pancreatic cancer by targeting the Hippo pathway.

New mechanical biomarkers were discovered and used to investigate drug effects on HeLa cells. HeLa cells were measured using advanced atomic force microscopy (AFM) techniques before and after treatment with an anticancer drug (docetaxel, a microtubule polymerizer) and the biomechanical properties of cells were analyzed using theoretical models. The biomechanical results show that the length of the surface brush, the factor of viscosity, and the adhesion work of untreated HeLa cells reduced from 920 nm, 0.72 and 4.12 × 10−16 N m to 673 nm, 0.52 and 5.37 × 10−17 N m for treated cells, respectively. In order to reveal the underlying mechanisms of these changes, transmission electron microscopy (TEM) and western blotting assays were employed to characterize structural changes of the cells. Compared to the untreated cells, TEM images confirmed a thinner brush layer on the surface of treated cells while the western blotting of tubulin extracted from the cells indicated an increased microtubule concentration for the treated cells. These changes are consistent with previous studies on the influence of docetaxel on cells. Based on the above results, we conclude that docetaxel can lead to an increased microtubule network in HeLa cells, a thinner brush layer on HeLa cell surfaces and that the length of surface brush, the factor of viscosity, and the adhesion work can be exploited as effective mechanical biomarkers to evaluate drug effects on HeLa cells. This work demonstrates a new AFM-based technique that can be exploited to assess drug action on cells and is promising for the application of drug screening.

Compared with traditional technologies, additive manufacture based on modern digital technology shows several advantages, such as high efficiency, freedom of design and near net shape, etc., providing new chances for the development of titanium alloys used in biomedical areas. This kind of “green manufacture” can also combine macroscopic contours of implants with the physical environment of defects to be repaired, thus improving the biomechanical compatibility and achieving good osseointegration between implants and human bones. This review summarizes the process and factors of AM technology, generalizes the microstructures, mechanical properties, biocompatibility in vitro and in vivo, and clinical application of titanium implants. The future prospects of AM technology in Ti-based implants have also been calculated.

The T7 peptide, an active fragment of full-length tumstatin [the non-collagenous 1 domain of the type IV collagen α3 chain, α3 (IV) NC1], has exhibited potential antitumor effects in several types of cancer cells. However, the mechanism underlying its action against human hepatocellular carcinoma (HCC) remains unclear. The present study aimed to investigate the role of autophagy in T7 peptide-induced cytotoxicity in HCC cells in vitro and in vivo. The results revealed that the T7 peptide significantly reduced cell viability and induced cell cycle arrest in HCC cells. The T7 peptide induced apoptosis in HCC cells through upregulation of Bax, Fas, and Fas ligand, and through upregulation of the anti-apoptotic protein Bcl-2. In addition, treatment with the T7 peptide induced protective autophagy in HCC cells. Blocking autophagy by 3-methyladenineor bafilomycin A1 enhanced T7 peptide-induced apoptosis. Furthermore, co-treatment with MK-2206 (an Akt specific inhibitor) or rapamycin (an inhibitor of mTOR) enhanced T7 peptide-induced autophagy, whereas co-treatment with insulin (an activator of the Akt/mTOR signaling pathway) alleviated T7 peptide-induced autophagy, which suggested that the T7 peptide may induce autophagy activation via inhibition of the Akt/mTOR signaling pathway. Taken together, the present results demonstrated that suppression of autophagy potentiated the cytotoxic effects of the T7 peptide, and suggested that the T7 peptide may serve as a potential alternative compound for HCC therapy.

3D printed porous titanium (Ti) holds enormous potential for load-bearing orthopedic applications. Although the 3D printing technique has good control over the macro-sturctures of porous Ti, the surface properties that affect tissue response are beyond its control, adding the need for tailored surface treatment to improve its osseointegration capacity. Here, the one step microarc oxidation (MAO) process was applied to a 3D printed porous Ti6Al4V (Ti64) scaffold to endow the scaffold with a homogeneous layer of microporous TiO2 and significant amounts of amorphous calcium-phosphate. Following the treatment, the porous Ti64 scaffolds exhibited a drastically improved apatite forming ability, cyto-compatibility, and alkaline phosphatase activity. In vivo test in a rabbit model showed that the bone in-growth at the untreated scaffold was in a pattern of distance osteogenesis by which bone formed only at the periphery of the scaffold. In contrast, the bone in-growth at the MAO-treated scaffold exhibited a pattern of contact osteogenesis by which bone formed in situ on the entire surface of the scaffold. This pattern of bone in-growth significantly increased bone formation both in and around the scaffold possibly through enhancement of bone formation and disruption of bone remodeling. Moreover, the implant surface of the MAO-treated scaffold interlocked with the bone tissues through the fabricated microporous topographies to generate a stronger bone/implant interface. The increased osteoinetegration strength was further proven by a push out test. MAO exhibits a high efficiency in the enhancement of osteointegration of porous Ti64 via optimizing the patterns of bone in-growth and bone/implant interlocking. Therefore, post-treatment of 3D printed porous Ti64 with MAO technology might open up several possibilities for the development of bioactive customized implants in orthopedic applications.

Mesoscale eddies can influence biogeochemical cycles through both vertical nutrient or plankton flux and horizontal advection of nutrient or plankton in eddy periphery. In this study, we analyzed the seasonal and spatial variability of near-sea-surface chlorophyll-a concentrations and their corresponding modulation mechanisms by collocating satellite observations of eddies tracked during 1998–2007 in the South China Sea. We found that in winter, cyclonic eddies show significantly high chlorophyll-a in the eddy core relative to the periphery, suggesting regulation by an eddy-pumping mechanism. While in summer, chlorophyll-a values in the core of cyclonic eddies are comparable with those in the periphery, and dipole features of chlorophyll-a around cyclonic eddies are conspicuous, which is largely induced by horizontal eddy advection. For anticyclonic eddies, however, low chlorophyll-a in eddy cores compared with the periphery are consistently present over most of the year. The impact of eddy advection on chlorophyll-a distribution in anticyclonic eddies is not clear from the composite images in different seasons. Variability of chlorophyll-a to the west of the Luzon Strait and northwest of the Luzon Island demonstrate that phytoplankton biomass in these two regions is mainly controlled by an eddy-pumping mechanism. In the regions off the Vietnam coast, chlorophyll-a distributions are generally associated with horizontal eddy advection. This research highlights different mesoscale mechanisms affecting biological structures in the upper ocean, which can potentially disturb ocean biogeochemical cycling processes in the South China Sea.

Protein arginine methylation is a common posttranslational modification resulting in the generation of asymmetric dimethylarginine (aDMA) and symmetric dimethylarginine (sDMA). Currently, the regulation of aDMA or sDMA by hypoxia, nutrient stavation or cytokines in the tumor microenvironment remains largely unknown. Here we show that p90aDMA, p70aDMA and p90sDMA, endogenous proteins containing aDMA or sDMA with mass 70 or 90 kDa, were widely and dominantly expressed in breast cancer cell lines. Notably, it was p90aDMA rather than p90sDMA that accumulated in the nucleus upon stimulation of cancer cells with interleukin (IL)-2, IL-4, IL-6 but not IL-8. In addition, the p90aDMA accumulation could be inhibited after treatment with a global methyltrasferase inhibitor, adenosine-2',3'-dialdehyde (AdOx). It seemed that some endogenous proteins in cancer cells were asymmetrically arginine-methylated upon exposure to some cytokines.. Furthermore, endogenous proteins of aDMA, such as p90aDMA and p70aDMA, were degraded in response to hypoxia, nutrient starvation and rapamycin treatment in breast and cervical cancer cells. IL-2/4/6 slightly increased basal autophagy but slightly decreased the rapamycin‑induced autophagy in cancer cells, suggesting that IL-2/4/6 and autophagy inducers play distinct roles in the regulation of aDMA of proteins. Conversely, rapamycin accumulated p90sDMA in MDA-MB‑231 and MCF-7 cells. Taken together, our results add a new dimension to the complexity of arginine methylated regulation in response to various stimuli and provide the first evidence that aDMA serves as one specific degradation signal of selective autophagy.

Phosphorene, a novel two-dimensional material with a puckered surface morphology, has been considered a potentially better alternative to graphene for future applications. Therefore, it is important to evaluate and compare the biological responses of phosphorene and graphene. In this paper, with large scale molecular dynamics simulations, the villin headpiece (HP35) was used as a model protein to investigate the disruption of protein’s structure (and function) caused by both phosphorene and graphene, for comparison of their biological responses. The results show that graphene’s disruption to the structure of HP35 is more severe, indicating that phosphorene’s interactions with HP35 are weaker as compared to graphene. Further analysis with two additional model materials, pseudo-phosphorene and pseudo-graphene, reveal that the puckered surface can have a significant effect in weakening the materials’ ability to disrupt proteins. These findings might shed light on understanding/designing the protein-nanomaterial interactions and would be helpful for the bioapplications of the new nanomaterial, phosphorene.

This study examines temporal variations of 234Th-based particle export based on time-series observations conducted from 2004 to 2014 at the South-East Asian Time-series Study (SEATS) site in the basin area of the Northern South China Sea. It shows significant variability in particle export at both seasonal and interannual time scales. A significant feature of our data as observed by prior studies is that particle export was high during the NE monsoon in winter, but low during the inter-monsoon and SW monsoon. Particle flux increased with increasing mixed layer depth (MLD), primarily in winter due to the presence of a strong NE monsoon, in addition to influence by mesoscale features quantified by eddy kinetic energy values. Particle export was generally elevated when phytoplankton biomass was abundant, as shown by the significant correlation between particle fluxes and concentrations of chlorophyll (Chl) a and/or particulate organic carbon (POC) between 0 and 100 m. This is also supported by the negative correlation between 234Th residence time and Chl a concentration, suggesting that increased phytoplankton biomass accelerated downward particle sinking. The correlation disappeared however at Chl a values

The resistance to sorafenib highly affects its clinical benefits for treating hepatocellular carcinoma (HCC). Sodium orthovanadate (SOV) is a phosphate analog that displays anti-cancer activities against various types of malignancies including HCC. The present study has demonstrated that SOV is able to overcome sorafenib resistance and strengthens sorafenib in suppressing sorafenib-resistant HCC cells in vitro and in animal models. Similar to its action on parental HCC cells, SOV induced cell cycle arrest at G2/M phases by regulating cyclin B1 and cyclin-dependent kinase 1, and apoptosis by reducing mitochondrial membrane potential, in sorafenib-resistant HCC cells. More importantly, SOV inhibited ATPase activity, which was significantly elevated in sorafenib-resistant HCC cells. SOV also reduced the expression of HIF-1α and HIF-2α and their nuclear translocation, resulting in downregulation of their downstream factors including vascular endothelial growth factor, lactate dehydrogenase-A and glucose transporter 1. Its ability to inhibit ATPase activity and hypoxia-inducible pathways enabled SOV to efficiently suppress both normoxic and hypoxic cells, which compose cancer cell populations inside sorafenib-resistant HCC tumors. The present results indicate that SOV may be a potent candidate drug for overcoming the resistance to sorafenib in treating HCC.

Mesoscale iron enrichment experiments have revealed that additional iron affects the phytoplankton productivity and carbon cycle. However, the role of initial size of fertilized patch in determining the patch evolution is poorly quantified due to the limited observational capability and complex of physical processes. Using a three-dimensional ocean circulation model, we simulated different sizes of inert tracer patches that were only regulated by physical circulation and diffusion. Model results showed that during the first few days since release of inert tracer, the calculated dilution rate was found to be a linear function with time, which was sensitive to the initial patch size with steeper slope for smaller size patch. After the initial phase of rapid decay, the relationship between dilution rate and time became an exponential function, which was also size dependent. Therefore, larger initial size patches can usually last longer and ultimately affect biogeochemical processes much stronger than smaller patches.

Ternary magnesium alloys with low combined addition of elements gadolinium and zinc were developed in the present work, with their microstructures, mechanical properties, in vitro degradation behaviors, and cytotoxicity being systematically studied. Furthermore, the Mg-1.8Zn-0.2Gd alloy, with the best in vitro performance, was implanted into Sprague Dawley rats to examine its in vivo degradation performance for up to 6 months. It was found that Mg-1.8Zn-0.2Gd, composed of a single α-Mg phase, owned excellent strength and toughness that were comparable to the CE marked MAGNEZIX, the mischmetal added Mg alloy. Owing to the uniform single-phased microstructure, the degradation rate of this alloy was around 0.12 mm/y measured by electrochemical testing, which was comparable to high purity magnesium. Moreover, the Mg-1.8Zn-0.2Gd alloy exhibited no cytotoxicity to L929, MG63, and VSMC cells. In vivo degradation characterized by micro-computed tomography revealed that the Mg-1.8Zn-0.2Gd implant could maintain structural integrity in the first 2 months, and serious degradation could be observed after 6 months. A remarkable 100% survival rate of experimental animals was observed with no negative effects on bone tissues. The implant and the surrounding bone were well integrated within 2 months, implying good biocompatibility and osteoconductivity of the experimental alloy. On the basis of the above findings, the feasibility of Mg-Zn-Gd alloys for use as orthopedic implants was systematically discussed. This study provides a new strategy for development of high-performance Mg-rare earth (RE)-based alloys with superior mechanical properties and corrosion resistance while effectively avoiding the possible standing toxic effect of RE elements.

Biogeochemical cycles associated with mesoscale eddies in the South China Sea (SCS) were investigated. The study was based on a coupled physical–biogeochemical Pacific Ocean model (Regional Ocean Model System–Carbon, Silicate, and Nitrogen Ecosystem, ROMS-CoSiNE) simulation for the period from 1991 to 2008. A total of 568 mesoscale eddies with lifetime longer than 30 days were used in the analysis. Composite analysis revealed that the cyclonic eddies were associated with abundance of nutrients, phytoplankton, and zooplankton while the anticyclonic eddies depressed biogeochemical cycles, which are generally controlled by the eddy pumping mechanism. In addition, diatoms were dominant in phytoplankton species due to the abundance of silicate. Dipole structures of vertical fluxes with net upward motion in cyclonic eddies and net downward motion in anticyclonic eddies were revealed. During the lifetime of an eddy, the evolutions of physical, biological, and chemical structures were not linearly coupled at the eddy core where plankton grew, and composition of the community depended not only on the physical and chemical processes but also on the adjustments by the predator–prey relationship.

Titanium-based implants possessing adequately low elasticity modulus and custom­designed structures are urgently demanded in recent years for orthopedic applications. Electron beam melting (EBM) provides an opportunity to fabricated porous titanium scaffolds that meet the as-mentioned requirements, and it further allows for improved bone regeneration and increased contact area at implant–tissue interface. As a novel additive manufacturing (AM) technique, EBM could conveniently produce scaffolds with tunable porosity and shapes and complex structures based on the popular “bottom-up” concept. In the present work, EBM-produced Ti6Al4V cylinders designed with either a small pore size (EBMS, 640 μm) or a large one (EBML, 1200 μm) were characterized in respect of microstructure, permeability and specific surface area, and their cytocompatibility and osteogenic ability were evaluated subsequently in vitro. Both samples EBMS and EBML could support the attachment and proliferation of hMSCs with minimal inflammatory cytokines secretion. The EBMS scaffolds were relatively more compatible with hMSCs than the EBML and they better sustained osteogenesis probably for their larger specific surface area.

The newly built CoSiNE-31 ecosystem model developed for the Pacific Ocean is employed here to evaluate carbon cycling in the equatorial Pacific upwelling region. This model explicitly includes 31 state variables capable of reproducing key biogeochemical features in this region, such as high-nutrient low-chlorophyll conditions. In the so-called Wyrtki Box (5°S–5°N, 90–180°W), the modeled area-averaged carbon export data show the predominance of the particulate organic carbon flux. This is consistent with observations, and amounts to 7.88 mmol C m–2 day–1 at the bottom of the euphotic zone (120 m water depth). Nearly as important is the dissolved organic carbon export flux, at 6.62 mmol C m–2 day–1. The modeled particulate inorganic carbon (PIC) export flux of 2.07 mmol C m–2 day–1 is much higher than the global average, indicating a key role of PIC sedimentation in the study region. The modeled carbon-to-nitrogen export ratio for particulate organic matter (POM) is 7.8, which is consistent with the Redfield ratio. The export ratio increases to 13.8 for dissolved organic matter (DOM). By implication, carbon export is markedly more efficient via DOM than via POM. This is the case also under simulated iron enrichment conditions, although there are measurable increases in carbon export efficiency for both DOM and POM.

From the perspective of element biosafety and dietetics, the ideal alloying elements for magnesium should be those which are essential to or naturally presented in human body. Element germanium is a unique metalloid in the carbon group, chemically similar to its group neighbors, Si and Sn. It is a dietary trace element that naturally presents in human body. Physiological role of Ge is still unanswered, but it might be necessary to ensure normal functioning of the body. In present study, novel magnesium alloys with dietary trace element Ge were developed. Feasibility of those alloys to be used as orthopaedic implant applications was systematically evaluated. Mg-Ge alloys consisted of α-Mg matrix and eutectic phases (α-Mg + Mg 2 Ge). Mechanical properties of Mg-Ge alloys were comparable to current Mg-Ca, Mg-Zn and Mg-Sr biodegradable metals. As-rolled Mg-3Ge alloy exhibited outstanding corrosion resistance in vitro (0.02 mm/y, electrochemical) with decent corrosion rate in vivo (0.6 mm/y, in rabbit tibia). New bone could directly lay down onto the implant and grew along its surface. After 3 months, bone and implant were closely integrated, indicating well osseointegration being obtained. Generally, this is a pioneering study on the in vitro and in vivo performances of novel Mg-Ge based biodegradable metals, and will benefit the future development of this alloy system. Statement of Significance The ideal alloying elements for magnesium-based biodegradable metals should be those which are essential to or naturally presented in human body. Element germanium is a unique metalloid in the carbon group. It is a dietary trace element that naturally presents in human body. In present study, feasibility of Mg-Ge alloys to be utilized as orthopedic applications was systematically investigated, mainly focusing on the microstructure, mechanical property, corrosion behavior and biocompatibility. Our findings showed that Mg-3Ge alloy exhibited superior corrosion resistance to current Mg-Ca, Mg-Zn and Mg-Sr alloys with favorable biocompatibility. This is a pioneering study on the in vitro & in vivo performances of Mg-Ge biodegradable metals, and will benefit the future development of this alloy system.

The purpose of this study was to investigate whether the therapeutic activity of gemcitabine (GCB) in hepatocellular carcinoma (HCC) could be increased by the down-regulation of secretory clusterin (sCLU), a glycoprotein that is considered to play a cytoprotective role in the resistance to chemotherapy. The expression of sCLU was detected in HCC tumor tissues and cell lines. A cell viability and apoptosis assay were performed in parental HCC cells or the same cells transfected with sCLU shRNA and treated with or without GCB. The potential downstream pathways were investigated using the Human Apoptosis RT2 Profiler™ PCR Array. The expression levels of sCLU in HCC tissues were significantly higher than in adjacent non-tumor liver tissues and were associated with the histological grade and transarterial chemoembolization. sCLU overexpression was also found in three HCC cell lines and hepatocytes. The depletion of sCLU synergistically increased GCB sensitivity in Bel7402 and SMMC7721 cells and induced cell apoptosis. Based on the PCR array analysis, sCLU depletion also resulted in the up-regulation of BNIP1, GADD45A, TNFRSF10A, and TRADD and down-regulation of AKT1 in Bel7402 and SMMC7721 cells compared with the parental controls. These results were further supported by a Western blot analysis, which showed increased GADD45a protein expression and the decreased expression of phosphorylated AKT. GADD45a overexpression also increased the sensitivity to GCB in the Bel7402 and SMMC7721 cells. Targeting sCLU may be a useful method to enhance the cytotoxic effect of GCB in hepatocellular carcinoma.

[1] In the study, the responses of chlorophyll to decadal oscillations of Kuroshio Extension (KE) between two dynamical states are investigated using satellite data. Associated with the KE stable and unstable states, the surface chlorophyll south of 35°N also undergoes two different contrast patterns: low (high) chlorophyll (∼12% relative to multiyear mean) corresponding to strengthened (weakened) KE jet, i.e., stable (unstable) KE. Two distinct seesaw patterns exist on the north and south side of 35°N for both chlorophyll and sea level anomaly and on the east and west side of 153°E for both chlorophyll and eddy kinetic energy. Similarly, the magnitude of spring bloom was also modulated by decadal variations of KE. The spring bloom was suppressed (enhanced) relative to the magnitude of climatological spring bloom south of 35°N during the KE stable (unstable) period. This change is significant and can reach 35% in extreme years of 2006 and 2009. The decadal variation of chlorophyll in the KE is likely modulated by vertical nutrient supply induced by divergences (convergences) associated with the westward propagation of wind-induced Rossby waves in the central and eastern North Pacific Ocean, which are dynamically modulated by the North Pacific Gyre Oscillations (NPGO) or PDO (Pacific Decadal Oscillations).

Restoring large-scale bone defects, where osteogenesis is slow while infections lurk, with biomaterials represents a formidable challenge in orthopedic clinics. Here, we propose a scaffold-based multipurpose anti-infection and bone repairing strategy to meet such restorative needs. To do this, personalized multifunctional titanium meshes were produced through an advanced additive manufacturing process and dual “TiO2–poly(dopamine)/Ag (nano)” post modifications, yielding macroporous constructs with micro-/nanoporous walls and nanosilver bullets immobilized/embedded therein. Ultrahigh loading capacity and durable release of Ag+ were accomplished. The scaffolds were active against planktonic/adherent bacteria (Gram-negative and positive) for up to 12 weeks. Additionally, they not only defended themselves from biofilm colonization but also helped destroy existing biofilms, especially in combination with antibiotics. Further, the osteoblasts/bacteria coculture study displayed that the engineered surfaces aided...

New evidences were provided that Kuroshio intrusion in winter is able to increase phytoplankton growth in the open ocean of the northern South China Sea (SCS) based on multiple data sources. Strong fronts due to Kuroshio intrusion and interactions with the SCS water are associated with intense upwelling, supplying high nutrients from the subsurface SCS water and increasing phytoplankton productivity in the frontal region. High chlorophyll is more dynamically related to these fronts than to the alongshore wind, wind stress curl, and eddy kinetic energy on interannual time scale. Further examinations suggest that fronts associated with Kuroshio intrusion into the SCS are linked with large-scale climate variability. During El Nino years, stronger Kuroshio intrusion results in stronger fronts that generate intensified local upwelling and enhanced Luzon winter blooms.

Understanding how nanomaterials interact with cell membranes is related to how they cause cytotoxicity and is therefore critical for designing safer biomedical applications. Recently, graphene (a two-dimensional nanomaterial) was shown to have antibacterial activity on Escherichia coli, but its underlying molecular mechanisms remain unknown. Here we show experimentally and theoretically that pristine graphene and graphene oxide nanosheets can induce the degradation of the inner and outer cell membranes of Escherichia coli, and reduce their viability. Transmission electron microscopy shows three rough stages, and molecular dynamics simulations reveal the atomic details of the process. Graphene nanosheets can penetrate into and extract large amounts of phospholipids from the cell membranes because of the strong dispersion interactions between graphene and lipid molecules. This destructive extraction offers a novel mechanism for the molecular basis of graphene's cytotoxicity and antibacterial activity.

With the widespread applications of nanomaterials such as carbon nanotubes, there is a growing concern on the biosafety of these engineered nanoparticles, in particular their interactions with proteins. In molecular simulations of nanoparticle-protein interactions, the choice of empirical parameters (force fields) plays a decisive role, and thus is of great importance and should be examined carefully before wider applications. Here we compare three commonly used force fields, CHARMM, OPLSAA, and AMBER in study of the competitive binding of a single wall carbon nanotube (SWCNT) with a native proline-rich motif (PRM) ligand on its target protein SH3 domain, a ubiquitous protein-protein interaction mediator involved in signaling and regulatory pathways. We find that the SWCNT displays a general preference over the PRM in binding with SH3 domain in all the three force fields examined, although the degree of preference can be somewhat different, with the AMBER force field showing the highest preference. The SWCNT prevents the ligand from reaching its native binding pocket by (i) occupying the binding pocket directly, and (ii) binding with the ligand itself and then being trapped together onto some off-sites. The pi-pi stacking interactions between the SWCNT and aromatic residues are found to play a significant role in its binding to the SH3 domain in all the three force fields. Further analyses show that even the SWCNT-ligand binding can also be relatively more stable than the native ligand-protein binding, indicating a serious potential disruption to the protein SH3 function.

The significance of the molecular chirality of drugs has been widely recognized due to the thalidomide tragedy. Most of the new drugs reaching the market today are single enantiomers, rather than racemic mixtures. However, many optically pure drugs, including thalidomide, undergo enantiomerization in vivo, thus negating the single enantiomers' benefits or inducing unexpected effects. A detailed atomic level understanding of chiral conversion, which is still largely lacking, is thus critical for drug development. Herein, we use first-principle density function theory (DFT) to explore the mechanism of enantiomerization of thalidomide. We have identified the two most plausible interconversion pathways for isolated thalidomide: 1) proton transfer from the chiral carbon center to an adjacent carbonyl oxygen atom, followed by isomerization and rotation of the glutarimide ring (before the proton hops back to the chiral carbon atom); and 2) a pathway that is the same as "1", but with the isomerization of the glutarimide ring occurring ahead of the initial proton transfer reaction. There are two remarkable energy barriers, 73.29 and 23.59 kcal mol(-1), corresponding to the proton transfer and the rotation of the glutarimide ring, respectively. Furthermore, we found that water effectively catalyzes the interconversion by facilitating the proton transfer with the highest energy barrier falling to approximately 30 kcal mol(-1), which, to our knowledge, is the first time that this important role of water in chiral conversion has been demonstrated. Finally, we show that the hydroxide ion can further lower the enantiomerization energy barrier to approximately 24 kcal mol(-1) by facilitating proton abstraction, which agrees well with recent experimental data under basic conditions. Our current findings highlight the importance of water and hydroxide ions in the enantiomerization of thalidomide and also provide new insights into the mechanism of enantiomerization at an atomic level.

The widespread application of nanomaterials has spurred an interest in the study of interactions between nanoparticles and proteins due to the biosafety concerns of these nanomaterials. In this review, a summary is presented of some of the recent studies on this important subject, especially on the interactions of proteins with carbon nanotubes (CNTs) and metallofullerenols. Two potential molecular mechanisms have been proposed for CNTs' inhibition of protein functions. The driving forces of CNTs' adsorption onto proteins are found to be mainly hydrophobic interactions and the so-called π-π stacking between CNTs' carbon rings and proteins' aromatic residues. However, there is also recent evidence showing that endohedral metallofullerenol Gd@C82 (OH)22 can be used to inhibit tumor growth, thus acting as a potential nanomedicine. These recent findings have provided a better understanding of nanotoxicity at the molecular level and also suggested therapeutic potential by using nanoparticles' cytotoxicity against cancer cells.

In a previous study, we explored the mechanism of urea-induced denaturation of proteins by performing molecular dynamics (MD) simulations of hen lysozyme in 8 M urea and supported the "direct interaction mechanism" whereby urea denatures protein via dispersion interaction (Hua, L.; Zhou, R. H.; Thirumalai, D.; Berne, B. J. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 16928). Here we perform large scale MD simulations of five representative protein/peptide systems in aqueous urea to investigate if the above mechanism is common to other proteins. In all cases, accumulations of urea around proteins/peptide are observed, suggesting that urea denatures proteins by directly attacking protein backbones and side chains rather than indirectly disrupting water structure as a "water breaker". Consistent with our previous case study of lysozyme, the current energetic analyses with five protein/peptide systems reveal that urea's preferential binding to proteins mainly comes from urea's stronger dispersion interactions with proteins than with bulk solution, whereas the electrostatic (hydrogen-bonded) interactions only play a relatively minor (even negative) role during this denaturation process. Furthermore, the simulations of the peptide system at different urea concentrations (8 and 4.5 M), and with different force fields (CHARMM and OPLSAA) suggest that the above mechanism is robust, independent of the urea concentration and force field used. Last, we emphasize the importance of periodic boundary conditions in pairwise energetic analyses. This article provides a comprehensive study on the physical mechanism of urea-induced protein denaturation and suggests that the "dispersion-interaction-driven" mechanism should be general.

We perform molecular dynamics simulations of narrow single-walled carbon nanotubes (SWNTs) in aqueous urea to investigate the structure and dynamical behavior of urea molecules inside the SWNT. Even at low urea concentrations (e.g., 0.5 M), we have observed spontaneous and continuous filling of SWNT with a one-dimensional urea wire (leaving very few water molecules inside the SWNT). The urea wire is structurally ordered, both translationally and orientationally, with a contiguous hydrogen-bonded network and concerted urea's dipole orientations. Interestingly, despite the symmetric nature of the whole system, the potential energy profile of urea along the SWNT is asymmetric, arising from the ordering of asymmetric urea partial charge distribution (or dipole moment) in confined environment. Furthermore, we study the kinetics of confined urea and find that the permeation of urea molecules through the SWNT decreases significantly (by a factor of ∼20) compared to that of water molecules, due to the stronger dispersion interaction of urea with SWNT than water, and a maximum in urea permeation happens around a concentration of 5 M. These findings might shed some light on the better understanding of unique properties of molecular wires (particularly the wires formed by polar organic small molecules) confined within both artificial and biological nanochannels, and are expected to have practical applications such as the electronic devices for signal transduction and multiplication at the nanoscale.

Reliable structural information of extremal points in a reaction is important but difficult to achieve in molecular chiral transitions under confinement due to the complex molecular interactions. In this Letter, based on statistical results of a number of classical molecular dynamics simulations, we found that a complete chiral transition process of a difluorobenzo[c]phenanthrene molecule (C18H12F2, called D molecule) within a single-walled boron-nitride nanotube involves at least five extremal point structures, showing a unique feature of chiral transition in the confined environment and suggesting an alternative to conventional first-principles calculations to determine the complex potential energy surface of intermolecular interactions.

Molecular dynamic simulations of the chiral transition of a difluorobenzo[c]phenanthrene molecule (C(18)H(12)F(2), D molecule) in single-walled boron-nitride nanotubes (SWBNNTs) revealed remarkable effects of the nanoscale confinement. The critical temperature, above which the chiral transition occurs, increases considerably with the nanotube diameter, and the chiral transition frequency decreases almost exponentially with respect to the reciprocal of temperature. The chiral transitions correlate closely with the orientational transformations of the D molecule. Furthermore, the interaction energy barriers between the D molecule and the nanotube for different orientational states can characterize the chiral transition. This implies that the temperature threshold of a chiral transition can be controlled by a suitable nanotube. These findings provide new insights to the effect of nanoscale confinement on molecular chirality.