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Abstract Background Lychee seeds were fermented by three kinds of bacteria (Lactobacillus plantarum, Saccharomyces cerevillus and ganoderma lucidum mycelium), and two effective strains were selected by two indexes of activity content and antioxidant, so as to further verify whether lychee seeds have waste multiplication effect and can protect cells damaged by oxidation from anti-inflammatory, anti-aging and safety. Results The contents of polyphenols, flavonoids and proteins in the solution fermented by Ganoderma lucidum mycelium did not increase, thus affecting the antioxidant capacity of the solution was far less than that of the water extract. The active content of the other two fermentation solutions was higher than that of the water extract, and the ability of scavenging free radicals of the two solutions increased with the increase of the volume fraction. At the cellular level, the two fermentation solutions showed repair effects on UVA-induced damaged cells. The contents of type I collagen (COL-1), total antioxidant capacity and ELN were increased, the contents of reactive oxygen species and MDA were decreased, and the expressions of inflammatory factors IL-6, TNF-a, iNOS and COX-2 were decreased in HaCaT cells. From the gene level, the mRNA contents of IL-6, TNF-a, Caspase-3, Caspase-9, Bax and Bcl were significantly decreased. The test of chick embryo chorioallantoic membrane (HTET CAM) showed that there was no bleeding and litchi seed fermentation liquid was not irritating. Conclusions Therefore, two kinds of litchi seed fermentation can be used as natural plant raw materials for cosmetics, and have strong antioxidant, anti-inflammatory and anti-aging functions on skin, and also have good human safety. Graphical Abstract

Abstract Global reanalyzes are widely used for investigations of Antarctic climate variability and change. The European Centre for Medium‐Range Weather Forecasts 5th generation reanalysis (ERA5) is well regarded and spans 1940 to today. We investigate whether ERA5 reliably represents the 2‐m air temperature trends across the 1940–2022 (83 years) period at seasonal and annual time scales. We compare ERA5 temperatures with an observation‐based temperature reconstruction for Antarctica (RECON) that has monthly resolution for 1958–2022, the period of reliable observational availability. Results for individual stations are also examined. ERA5 anomalously warms Antarctica in relation RECON especially for the period prior to 1979 when satellite observations over the Southern Ocean were sparse. Trend hotspots that are shown to be artifacts are found at three locations and are present until today. The results demonstrate that ERA5 temperature trends can be questionable even today, but variability is well captured after 1979.

Abstract The Antarctic Peninsula (AP) experienced a new extreme warm event and record-high surface melt in February 2022, rivaling the recent temperature records from 2015 and 2020, and contributing to the alarming series of extreme warm events over this region showing stronger warming compared to the rest of Antarctica. Here, the drivers and impacts of the event are analyzed in detail using a range of observational and modeling data. The northern/northwestern AP was directly impacted by an intense atmospheric river (AR) attaining category 3 on the AR scale, which brought anomalous heat and rainfall, while the AR-enhanced foehn effect further warmed its northeastern side. The event was triggered by multiple large-scale atmospheric circulation patterns linking the AR formation to tropical convection anomalies and stationary Rossby waves, with an anomalous Amundsen Sea Low and a record-breaking high-pressure system east of the AP. This multivariate and spatial compound event culminated in widespread and intense surface melt across the AP. Circulation analog analysis shows that global warming played a role in the amplification and increased probability of the event. Increasing frequency of such events can undermine the stability of the AP ice shelves, with multiple local to global impacts, including acceleration of the AP ice mass loss and changes in sensitive ecosystems.

Introduction: Sanjin tablets (SJT) are a well-known Chinese patent drug that have been used to treat urinary tract infections (UTIs) for the last 40 years. The drug consists of five herbs, but only 32 compounds have been identified, which hinders the clarification of its effective substances and mechanism.Methods: The chemical constituents of SJT and their effective substances and functional mechanism involved in the treatment of UTIs were investigated by using high performance liquid chromatography-electrospray ionization-ion trap-time of flight-mass spectrometry (HPLC-ESI-IT-TOF-MSn), network pharmacology, and molecular docking.Results: A total of 196 compounds of SJT (SJT-MS) were identified, and 44 of them were unequivocally identified by comparison with the reference compounds. Among 196 compounds, 13 were potential new compounds and 183 were known compounds. Among the 183 known compounds, 169 were newly discovered constituents of SJT, and 93 compounds were not reported in the five constituent herbs. Through the network pharmacology method, 119 targets related to UTIs of 183 known compounds were predicted, and 20 core targets were screened out. Based on the “compound–target” relationship analysis, 94 compounds were found to act on the 20 core targets and were therefore regarded as potential effective compounds. According to the literature, 27 of the 183 known compounds were found to possess antimicrobial and anti-inflammatory activities and were verified as effective substances, of which 20 were first discovered in SJT. Twelve of the 27 effective substances overlapped with the 94 potential effective compounds and were determined as key effective substances of SJT. The molecular docking results showed that the 12 key effective substances and 10 selected targets of the core targets have good affinity for each other.Discussion: These results provide a solid foundation for understanding the effective substances and mechanism of SJT.

In order to assess the unique beauty of Tongjian Lake in Hangzhou, 80 sample photographs were selected for landscape beauty degree assessment using the Scenic Beauty Estimation method. The 14 characteristic influencing factors of landscape photos were extracted according to the Scenic Beauty Estimation value, and the influencing factors with insignificant differences and small bias correlation coefficients were eliminated through multiple linear regression analysis. The results showed that the main factors affecting the expression of the beauty of Tongjian Lake were water ecology, greenway morphology, landscape openness, water area ratio, vegetation color richness, and vignette matching. Combining the abovementioned analysis results, the two-dimensional plan, isometric map, and three-dimensional space are combined to show the main factors in a visual way, and on this basis, the corresponding optimization strategy is proposed. It provides a reference for future urban waterfront greenway landscape creation.

PurposeTo evaluate the correlation between microvascular density (MVD) and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) parameters and the effect of glycolytic flux after transarterial chemoembolization (TACE) in a rabbit VX2 liver tumor.Materials and methodsVX2 liver tumor allografts in 15 New Zealand white rabbits were treated with sterile saline (control group, n = 5) or lipiodol-doxorubicin emulsion (experimental group, n = 10). MRI was performed 2 weeks after the procedure to evaluate IVIM parameters, including apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF). All animal samples were taken of the tumor and surrounding liver. Immunostaining for CD31, CD34, CD105, and VEGF was used to evaluate MVD. The protein expression of Glut4, HK2, PKM2, LDHA, and MCT1 was determined using western blotting. Pearson correlation tests were used to analyze the relationship between MVD and IVIM parameters.ResultsD* value in the peritumoral region was negatively correlated with CD34 (r = –0.71, P = 0.01). PF value positively correlated with CD34 (r = 0.68, P = 0.015), CD105 (r = 0.76, P = 0.004) and VEGF (r = 0.72, P = 0.008) in the peritumoral region. Glut4, HK2, PKM2, and MCT1 in the peritumoral regions were higher in the experimental group than in the control group (all P < 0.05).ConclusionIVIM parameters were correlated with MVD in the intratumoral and peritumoral regions after TACE in a rabbit liver tumor model. The angiogenesis reflected by MVD may be related to changes of glycolytic flux.

Abstract The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss‐of‐function and gain‐of‐function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production.

In order to improve the positioning accuracy and motion stability of endoscopy surgery robot with remote motion center (RCM) of slave manipulator，the equivalent centroid position of the component is obtained by dynamic equivalence of slave manipulator，and the gravity compensation of the manipulator is carried out by the pull spring-rope wheel. Then the dynamic model of RCM mechanism from the slave manipulator is established according to the Lagrange equation，and the gravity compensation is carried out by the method of calculating moment. By comparing and analyzing the motion response curves of each joint of the manipulator after gravity compensation with Adams，it shows that gravity compensation model can effectively compensate gravity items.

Abstract Circular RNA (circRNAs) functions vital in the pathogenesis and progression of hepatocellular carcinoma (HCC). However, the expressions and functions of certain circRNAs on metastasis and proliferation of that cancer is still unclear. Bioinformation analysis and qRT-PCR indicated that CircC16orf62 was prominent upregulated in HCC of which the expression level was positively associated to cancer’s malignant progression. Gain or loss-of-function studies indicated that the reduction of CircC16orf62 expression promotes the proliferation, invasion, and glycolysis of HCC in vitro and in vivo. The bioinformatic analysis found that miR-138-5p and PTK2 were the downstream target of CircC16or62. Then, the FISH(Fluorescence immunoin situ hybridization) and cell nucleoplasmic separation determined that CircC16orf62 located in the cell cytoplasm. Plasmid vectors or siRNAs were used to change the expression of CircC16orf62, miR-138-5p, and PTK2 in PC cell lines. CircC16orf62 functioned as a molecular sponge for miR-138-5p, and a competitive endogenous RNA for PTK2, promoting AKT/mTOR pathway activation. Our observations lead us to conclude that CircC16orf62 functions as an oncogene in HCC progression, behaving as a competitive endogenous RNA for miR-138-5p binding, thus activating the AKT/mTOR pathway. In conclusion, CircC16orf62 is an oncogene through the miR-138-5p/PTK2/Akt axis in HCC cells, indicating CircC16orf62 can be a therapeutic target with potentiality for liver cancer and a predictive marker for people with HCC.

Abstract The development of biosimilar products or follow-on biologics has been flourishing in recent years because of their lower price than the originators. In this study, a multivariate data analysis method based on JMP software was proposed to assess the glycosylation pattern similarity of antibody candidates from different conditions in optimization experiments with a reference. A specific distance was generated by this method and indicated the glycoform similarity between the biosimilar and the reference. This method can be applied to analyze the similarity of other physicochemical and functional characteristics between follow-on biologics and originators. Then, the design of experimental methods can be realized to optimize the conditions of cell culture to attain similar antibody candidates. A higher concentration of GlcNAc added to the basal media made the glycan of the antibody more similar to the glycan of the reference in this study.

Abstract Glycosylation is critical for monoclonal antibody production because of its impact on pharmacokinetics and pharmacodynamics. Modulation of glycan profile is frequently needed in biosimilar development. However, glycosylation profile is not a single value like that of cell culture titer, hence making it challenging for the Design of Experiment (DoE) methodology to be directly applied. In this study, a Her2-binding antibody was developed as a biosimilar to Herceptin. Cluster analysis was introduced to demonstrate the similarity of glycan profiles between the samples and the reference with specific value—distance. The glycosylation was subsequently optimized with the DoE method. Basal medium and feed medium were found to be the significant factors to the glycosylation pattern. Moreover, a combination of medium and feed strategy was developed to attain the most similar glycoprotein molecule to that of the originator biologic drug. This study may provide an additional option to evaluate multivariable factors and assess biosimilarity and/or comparability in monoclonal antibody production.

The surgical robots with remote motion center （RCM） play an important role in the field of minimally invasive surgery （MIS）. Considering the advantages and disadvantages of double parallelogram and double synchronous belt RCM mechanism， a new RCM mechanism based on single synchronous belt， single parallelogram is proposed. Based on Adams and SimMechanics， the accuracy and workspace of the fixed point at the end of the new RCM mechanism are analyzed. The simulation results show that the new RCM mechanism has higher fixed point accuracy， simple and compact mechanism and good stability on the basis of meeting the motion space required by the operation.

We propose a method based on neural networks to accurately predict hydration sites in proteins. In our approach, high-quality data of protein structures are used to parametrize our neural network model, which is a differentiable score function that can evaluate an arbitrary position in 3D structures on proteins and predict the nearest water molecule that is not present. The score function is further integrated into our water placement algorithm to generate explicit hydration sites. In experiments on the OppA protein dataset used in previous studies and our selection of protein structures, our method achieves the highest model quality in terms of F1 score, compared to several previous studies.

Abstract Background X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by germline mutations in the Bruton tyrosine kinase (BTK) gene on X chromosome. These mutations disturb B-cell development, decrease immunoglobulin levels, increase susceptibility to infection or neoplasms, and increase the risk of developing colorectal cancer (CRC). For occasional cases of CRC have been reported in XLA patients, low levels of B lymphocytes and immunoglobulins induced by congenital immune disorder make them more susceptible to drug-related toxicities (DRT). Therefore, gene sequencing, therapeutic drug monitoring and any possible measurement to predict DRT should be considered before determining the course of chemotherapy for XLA patients with CRC. Case presentation In this study, we reported a 21-year-old male who developed metastatic CRC in the context of XLA. Since the whole exome sequencing and therapeutic drug monitoring did not reveal any predictive markers of DRT, we applied standard first-line chemotherapy to the patient. However, progressive disease occurred after the fifth treatment cycle. Therefore, the administration of oxaliplatin was changed to irinotecan as second-line therapy. After that, the patient firstly suffered from severe hypocalcemia and eventually died due to metastatic CRC after the eighth treatment cycle. The overall survival time was 7.5 months. Conclusions This study reported the first written record of a Chinese XLA patient with metastatic CRC and severe hypocalcemia. Whole exome sequencing and bioinformatic analysis indicated the somatic mutations in ABCA6, C6 and PAX3 genes might contribute to the early-onset and metastasis CRC. Besides, a number of germline mutations in genes related to calcium metabolism (CACNA2D4, CD36, etc.) and the administration of irinotecan were speculated to be the causes of severe hypocalcemia. We therefore suggested that in order to avoid severe DRT, clinicians should take genetic background and therapeutic drug monitoring into consideration while planning chemotherapy treatment for XLA patients with CRC.

The fluctuation of groundwater causes a change in the groundwater environment and then affects the migration and transformation of pollutants. To study the influence of water level fluctuations on nitrogen migration and transformation, physical experiments on the nitrogen migration and transformation process in the groundwater level fluctuation zone were carried out. A numerical model of nitrogen migration in the Vadose zone and the saturated zone was constructed by using the software HydrUS-1D. The correlation coefficient and the root mean square error of the model show that the model fits well. The numerical model is used to predict nitrogen migration and transformation in different water level fluctuation scenarios. The results show that, compared with the fluctuating physical experiment scenario, when the fluctuation range of the water level increases by 5 cm, the fluctuation range of the nitrogen concentration in the coarse sand, medium sand and fine sand media increases by 37.52%, 31.40% and 21.14%, respectively. Additionally, when the fluctuation range of the water level decreases by 5 cm, the fluctuation range of the nitrogen concentration in the coarse sand, medium sand and fine sand media decreases by 36.74%, 14.70% and 9.39%, respectively. The fluctuation of nitrogen concentration varies most significantly with the amplitude of water level fluctuations in coarse sand; the change in water level has the most significant impact on the flux of nitrate nitrogen and has little effect on the change in nitrite nitrogen and ammonium nitrogen, and the difference in fine sand is the most obvious, followed by medium sand, and the difference in coarse sand is not great.

Forecasting Antarctic atmospheric, oceanic, and sea ice conditions on subseasonal to seasonal scales remains a major challenge. During both the freezing and melting seasons current operational ensemble forecasting systems show a systematic overestimation of the Antarctic sea-ice edge location. The skill of sea ice cover prediction is closely related to the accuracy of cloud representation in models, as the two are strongly coupled by cloud radiative forcing. In particular, surface downward longwave radiation (DLW) deficits appear to be a common shortcoming in atmospheric models over the Southern Ocean. For example, a recent comparison of ECMWF reanalysis 5th generation (ERA5) global reanalysis with the observations from McMurdo Station revealed a year-round deficit in DLW of approximately 50 Wm ^−2 in marine air masses due to model shortages in supercooled cloud liquid water. A comparison with the surface DLW radiation observations from the Ocean Observatories Initiative mooring in the South Pacific at 54.08° S, 89.67° W, for the time period January 2016–November 2018, confirms approximately 20 Wm ^−2 deficit in DLW in ERA5 well north of the sea-ice edge. Using a regional ocean model, we show that when DLW is artificially increased by 50 Wm ^−2 in the simulation driven by ERA5 atmospheric forcing, the predicted sea ice growth agrees much better with the observations. A wide variety of sensitivity tests show that the anomalously large, predicted sea-ice extent is not due to limitations in the ocean model and that by implication the cause resides with the atmospheric forcing.

Because of the nitrogen pollution problem in groundwater, the migration conversion mechanism of nitrogen in groundwater level fluctuations was analyzed. Technology and methods through indoor experiments and theoretical analysis were used to study coarse sand, medium sand, and fine sand groundwater level fluctuation in the aeration zone and saturated zone under the situation of nitrogen distribution characteristics, revealing groundwater level fluctuation with the nitrogen migration mechanism. The experimental results showed that the variation range of the nitrate-nitrogen (NO3−−N) concentration with the water level is medium sand > fine sand > coarse sand. The ammonium nitrogen (NH4+−N) concentration showed a downward trend after water level fluctuations, and there were more apparent fluctuations in coarse sand and medium sand. The nitrite nitrogen (NO2−−N) in coarse sand and medium sand first increased the water level and then gradually reached a balance. The sampling points below the water level in fine sand showed a downward trend with fluctuation of the water level, and then gradually reached equilibrium. The results provide a scientific basis for the remediation and treatment of soil and groundwater pollution.

This paper proposes a trajectory-based optimal area forwarding (TOAF) algorithm tailored for multihop data delivery from infrastructure nodes (e.g., Internet access points) to moving vehicles (infrastructure-to-vehicle) in vehicular ad hoc networks (VANETs) with partial deployment of stationary nodes. It focuses on reducing the delivery-delay jitter and improving the low reliability of infrastructure-to-vehicle communication. To adapt with the real world, TOAF supposes that stationary nodes are partially installed at intersections in VANETs, and nodes' trajectories can be calculated and predicted, such as using cloud services and GPS, to find the optimal area where the destination vehicle may receive a packet timely. AP selects the optimal area from the trajectory of the destination vehicle and determines the delivery sequence, which includes stationary and mobile nodes from the AP to the optimal area. During delivery, if a new node finds that the delay to the next stationary node is less than that of the current carrier, it can be added to the sequence, reducing the delivery delay. The addition of a new node continues until the packet reaches the optimal area and infrastructure-to-vehicle communication is achieved. The simulation results confirm that TOAF can improve the performance of delivery-delay jitters and reliability of infrastructure-to-vehicle communication with partial deployment of stationary nodes.

Atmospheric rivers (ARs) are the primary mechanism for transporting water vapor from low latitudes to polar regions, playing a significant role as drivers of extreme weather, such as heavy precipitation and heat waves in both the Arctic and Antarctica. With the rapidly growing interest in polar ARs during the past decade, it is imperative to establish an objective framework to quantify the strength and impact of these ARs for both scientific research and practical application. The AR scale introduced by Ralph et al. (2019) ranks ARs based on the duration of AR conditions and the intensity. However, the thresholds of integrated water vapor transport (IVT) used to rank ARs are selected based on the IVT climatology at middle latitudes. These thresholds are insufficient for polar regions due to the substantially lower temperature and moisture content. In this study, we analyze the IVT climatology in polar regions, focusing on the coasts of Antarctica and Greenland. Then we introduce an extended version of the AR scale tuned to polar regions by adding lower IVT thresholds of 100, 150, and 200 kg m-1 s-1 to the standard AR scale, which starts at 250 kg m-1 s-1. The polar AR scale is utilized to examine AR frequency, seasonality, trends, and associated precipitation and surface melt over the Antarctic and Greenland coasts. The polar AR scale better characterizes the strength and impacts of ARs in the Antarctic and Arctic regions, and has the potential to enhance communications across observation, research, and forecasts for polar regions. [ABSTRACT FROM AUTHOR]

Abstract. The Ross Ice Shelf, West Antarctica, experienced an extensive melt event in January 2016. We examine the representation of this event by the HIRHAM5 and MetUM high-resolution regional atmospheric models, as well as a sophisticated offline coupled firn model forced with their outputs. The model results are compared with satellite-based estimates of melt days. The firn model estimates of the number of melt days are in good agreement with the observations over the eastern and central sectors of the ice shelf, while the HIRHAM5 and MetUM estimates based on their own surface schemes are considerably underestimated, possibly due to deficiencies in these schemes and an absence of spin-up. However, the firn model simulates sustained melting over the western sector of the ice shelf, in disagreement with the observations that show this region as being melt-free. This is attributed to deficiencies in the HIRHAM5 and MetUM output, and particularly a likely overestimation of nighttime net surface radiative flux. This occurs in response to an increase in nighttime downwelling longwave flux from around 180-200 W m-2 to 280 W m-2 over the course of a few days, leading to an excessive amount of energy at the surface available for melt. Satellite-based observations show that this change coincides with a transition from clear-sky conditions to clouds containing both liquid-water and ice-water. The models capture the initial clear-sky conditions but seemingly struggle to correctly represent the ice-to-liquid mass partitioning associated with the cloudy conditions, which we suggest is responsible for the radiative flux errors. [ABSTRACT FROM AUTHOR]

We calculate a regional surface "melt potential" index (MPI) over Antarctic ice shelves that describes the frequency (MPI-freq; %) and intensity (MPI-int; K) of daily maximum summer temperatures exceeding a melt threshold of 273.15 K. This is used to determine which ice shelves are vulnerable to melt-induced hydrofracture and is calculated using near-surface temperature output for each summer from 1979/80 to 2018/19 from two high-resolution regional atmospheric model hindcasts (using the MetUM and HIRHAM5). MPI is highest for Antarctic Peninsula ice shelves (MPI-freq 23%-35%, MPI-int 1.2-2.1 K), lowest (2%-3%, 0 K) for the Ronne-Filchner and Ross ice shelves, and around 10%-24% and 0.6-1.7 K for the other West and East Antarctic ice shelves. Hotspots of MPI are apparent over many ice shelves, and they also show a decreasing trend in MPI-freq. The regional circulation patterns associated with high MPI values over West and East Antarctic ice shelves are remarkably consistent for their respective region but tied to different large-scale climate forcings. The West Antarctic circulation resembles the central Pacific El Niño pattern with a stationary Rossby wave and a strong anticyclone over the high-latitude South Pacific. By contrast, the East Antarctic circulation comprises a zonally symmetric negative Southern Annular Mode pattern with a strong regional anticyclone on the plateau and enhanced coastal easterlies/weakened Southern Ocean westerlies. Values of MPI are 3-4 times larger for a lower temperature/melt threshold of 271.15 K used in a sensitivity test, as melting can occur at temperatures lower than 273.15 K depending on snowpack properties. [ABSTRACT FROM AUTHOR]