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Herein the one‐pot thioesterification and hydrothiolation of α, β‐unsaturated esters with aliphatic thiols was reported at room temperature. The mechanism was indirectly revealed which α, β‐unsaturated thioester was the intermediate. The advantages of this method included transition‐metal‐free, mild conditions, broad substrate scope and good functional group tolerance. On the other hand, the hydrothiolation of α, β‐unsaturated aliphatic esters at room temperature was also developed. [ABSTRACT FROM AUTHOR]

The MEF2D rearrangement is a recurrent chromosomal abnormality detected in approximately 2.4–5.3% of patients with acute B-cell lymphoblastic leukemia (B-ALL). Currently, MEF2D-rearranged B-ALL is not classified as an independent subtype in the WHO classification. Consequently, the clinical significance of MEF2D rearrangement in B-ALL remains largely unexplored. In this study, we retrospectively screened 260 B-ALL patients with RNA sequencing data collected between November 2018 and December 2022. Among these, 10 patients were identified with MEF2D rearrangements (4 with MEF2D::HNRNPUL1, 3 with MEF2D::BCL9, 1 with MEF2D::ARID1B, 1 with MEF2D::DAZAP1 and 1 with MEF2D::HNRNPM). Notably, HNRNPM and ARID1B are reported as MEF2D fusion partners for the first time. The patient with the MEF2D::HNRNPM fusion was resistant to chemotherapy and chimeric antigen receptor T-cell therapy and relapsed early after allogenic stem cell transplantation. The patient with MEF2D::ARID1B experienced early extramedullary relapse after diagnosis. All 10 patients achieved complete remission after induction chemotherapy. However, 9/10 (90%) of whom experienced relapse. Three of the 9 patients relapsed with aberrant expression of myeloid antigens. The median overall survival of these patients was only 11 months. This small cohort showed a high incidence of early relapse and short survival in patients with MEF2D rearrangements. [ABSTRACT FROM AUTHOR]

Rock damage model is of great significance to the forecast of rock failure in engineering design such as tunnel, drilling, stability of slope, and mine. However, the applicability of statistical damage constitutive models and efficient model selection criteria of rock have not been fully investigated, which leads to difficulties in resolving issues practice via employing models. In the paper, we developed a rock damage constitutive model based on power law distribution and investigated the corresponding applicability in describing rock damage behavior. The uniaxial compression tests for different rocks (e.g., sandstone, granite, mudstone, shale, and marble) are carried out to verify the applicability of the model, and the criterion for model selection is proposed based on the rock porosity strain ratio. The results show that the proposed model exhibits better performance in predicting variation for the brittle rock damage compared with the common damage model based on Weibull distribution. Besides, the applicability of the proposed model can be extended to elastic–plastic rock by adopting the sigmoid function. The research in this study provides an effective model to describe rock damage behavior for brittle and elastic–plastic and presents a criterion for model selection. [ABSTRACT FROM AUTHOR]

This paper investigates the structural performance of a new prefabricated H-shaped steel beam assembled using high-strength bolts under three-point bending. The study evaluates four bolt hole types in five layout schemes through experimental tests. The results show that specimens with standard round holes in both the H-shaped steel and connecting plates exhibited 11% to 30% higher flexural bearing capacity compared to other hole types. Additionally, ANSYS simulations closely matched the experimental results, with a 6% difference. The research results provide important references for the design of prefabricated H-shaped steel beams with different bolt hole types, offering a practical foundation for enhancing the flexural performance of steel beam designs. [ABSTRACT FROM AUTHOR]

Diarrheal disease continues to be a major cause of global morbidity and mortality among children under 5 years of age. To address the current issues associated with oral attenuated rotavirus vaccines, the study of parenteral rotavirus vaccines has promising prospects. In our previous study, we reported that rotavirus nonstructural protein 4 (NSP4) did not increase the IgG antibody titer of co-immune antigen but did have a protective effect against diarrhea via the intramuscular injection method. Here, we explored whether NSP4 can exert adjuvant effects on mucosal immune pathways. In this study, we immunized mice via muscle and nasal routes, gavaged them with the rotavirus Wa strain or the rotavirus SA11 strain, and then tested the protective effects of immune sera against both viruses. The results revealed that the serum-specific VP8* IgG antibody titers of the mice immunized via the nasal route were much lower than those of the mice immunized by intramuscular injection, and the specific IgA antibodies were almost undetectable in the bronchoalveolar lavage fluid (BALF). NSP4 did not increase the titer of specific VP8* antibodies in either immune pathway. Therefore, in the two vaccines (PP-NSP4-VP8* and PP-VP8*+NSP4) used in this study, NSP4 was unable to perform its potential adjuvant role through the mucosal immune pathway. Instead, NSP4 was used as a co-immunized antigen to stimulate the mice to produce specific binding antibodies that play a protective role against diarrhea. [ABSTRACT FROM AUTHOR]

The article focuses on comparing the efficacy of venetoclax plus hypomethylating agents (VEN + HMA) versus intensive chemotherapy in treating acute myeloid leukemia with myelodysplasia-related gene mutations (AML-MR). Topics include the impact of genetic mutations on treatment decisions, the outcomes of VEN + HMA compared to standard chemotherapy, and the effects of different treatment regimens on overall and event-free survival rates in AML-MR patients.

Thrombotic diseases, emerging as a global public health hazard with high mortality and disability rates, pose a significant threat to human health and longevity. Although current antithrombotic therapies are effective in treating these conditions, they often carry a substantial risk of bleeding, highlighting the urgent need for safer therapeutic alternatives. Recent evidence has increasingly pointed to a connection between elastase activity and thrombosis. In the current study, we investigated the antithrombotic effects of ShSPI, an elastase inhibitor peptide derived from the venom of Scolopendra hainanum. Results showed that ShSPI significantly attenuated carrageenan-induced thrombosis in vivo. Furthermore, ShSPI effectively inhibited the carrageenan-induced decrease in serum superoxide dismutase (SOD) activity and increase in prothrombin time, fibrinogen level, and endothelial nitric oxide synthase (eNOS) activity. In addition, ShSPI reduced intracerebral thrombosis and improved functional outcomes following ischemic stroke in a transient middle cerebral artery occlusion (tMCAO) mouse model. Collectively, these findings suggest that ShSPI is a promising candidate for the development of novel thrombotic therapies. [ABSTRACT FROM AUTHOR]

Background: The molecular mechanisms underlying nonalcoholic fatty liver disease (NAFLD) remain to be fully elucidated. Ubiquitin specific protease 13 (USP13) is a critical participant in inflammation-related signaling pathways, which are linked to NAFLD. Herein, the roles of USP13 in NAFLD and the underlying mechanisms were investigated. Methods: L02 cells and mouse primary hepatocytes were subjected to free fatty acid (FFA) to establish an in vitro model reflective of NAFLD. To prepare in vivo model of NAFLD, mice fed a high-fat diet (HFD) for 16 weeks and leptin-deficient (ob/ob) mice were used. USP13 overexpression and knockout (KO) strategies were employed to study the function of USP13 in NAFLD in mice. Results: The expression of USP13 was markedly decreased in both in vitro and in vivo models of NAFLD. USP13 overexpression evidently inhibited lipid accumulation and inflammation in FFA-treated L02 cells in vitro. Consistently, the in vivo experiments showed that USP13 overexpression ameliorated hepatic steatosis and metabolic disorders in HFD-fed mice, while its deficiency led to contrary outcomes. Additionally, inflammation was similarly attenuated by USP13 overexpression and aggravated by its deficiency in HFD-fed mice. Notably, overexpressing of USP13 also markedly alleviated hepatic steatosis and inflammation in ob/ob mice. Mechanistically, USP13 bound to transforming growth factor β-activated kinase 1 (TAK1) and inhibited K63 ubiquitination and phosphorylation of TAK1, thereby dampening downstream inflammatory pathways and promoting insulin signaling pathways. Inhibition of TAK1 activation reversed the exacerbation of NAFLD caused by USP13 deficiency in mice. Conclusions: Our findings indicate the protective role of USP13 in NAFLD progression through its interaction with TAK1 and inhibition the ubiquitination and phosphorylation of TAK1. Targeting the USP13-TAK1 axis emerges as a promising therapeutic strategy for NAFLD treatment. [ABSTRACT FROM AUTHOR]

Wavefront control is the fundamental requirement in optical informatics. Planar optics have drawn intensive attention due to the merits of compactness and light weight. However, it remains a challenge to freely manipulate the dispersion, hindering practical applications, especially in imaging. Here, we propose the concept of frequency-synthesized phase engineering to solve this problem. A phasefront-frequency matrix is properly designed to encode different spatial phases to separate frequencies, thus makes arbitrary dispersion tailoring and even frequency-separated functionalization possible. The periodically rotated director endows cholesteric liquid crystal with a spin and frequency selective reflection. Moreover, via presetting the local initial orientation of liquid crystal, geometric phase is encoded to the reflected light. We verify the proposed strategy by cascading the chiral anisotropic optical media of specifically designed helical pitches and initial director orientations. By this means, planar lenses with RGB achromatic, enhanced chromatic aberration and color routing properties are demonstrated. Inch-sized and high-efficient lenses are fabricated with low crosstalk among colors. It releases the freedom of dispersion control of planar optics, and even enables frequency decoupled phase modulations. This work brings new insights to functional planar optics and may upgrade the performance of existing optical apparatuses. [ABSTRACT FROM AUTHOR]

Wavefront control is the fundamental requirement in optical informatics. Planar optics have drawn intensive attention due to the merits of compactness and light weight. However, it remains a challenge to freely manipulate the dispersion, hindering practical applications, especially in imaging. Here, we propose the concept of frequency-synthesized phase engineering to solve this problem. A phasefront-frequency matrix is properly designed to encode different spatial phases to separate frequencies, thus makes arbitrary dispersion tailoring and even frequency-separated functionalization possible. The periodically rotated director endows cholesteric liquid crystal with a spin and frequency selective reflection. Moreover, via presetting the local initial orientation of liquid crystal, geometric phase is encoded to the reflected light. We verify the proposed strategy by cascading the chiral anisotropic optical media of specifically designed helical pitches and initial director orientations. By this means, planar lenses with RGB achromatic, enhanced chromatic aberration and color routing properties are demonstrated. Inch-sized and high-efficient lenses are fabricated with low crosstalk among colors. It releases the freedom of dispersion control of planar optics, and even enables frequency decoupled phase modulations. This work brings new insights to functional planar optics and may upgrade the performance of existing optical apparatuses. [ABSTRACT FROM AUTHOR]

The primary radiation damage in pure V and TiVTa concentrated solid-solution alloy (CSA) was studied using a molecular dynamics method. We have performed displacement cascade simulations to explore the generation and evolution behavior of irradiation defects. The results demonstrate that the defect accumulation and agglomeration in TiVTa CSA are significantly suppressed compared to pure V. The peak value of Frenkel pairs during cascade collisions in TiVTa CSA is much higher than that in pure V due to the lower formation energy of point defects. Meanwhile, the longer lifetime of the thermal spike relaxation and slow energy dissipation capability of TiVTa CSA can facilitate the recombination of point defects. The defect agglomeration rate in TiVTa CSA is much lower due to the lower binding energy of interstitial clusters and reduced interstitial diffusivity. Furthermore, the occurrence probability of dislocation loops in TiVTa CSA is lower than that in pure V. The reduction in primary radiation damage may enhance the radiation resistance of TiVTa CSA, and the improved radiation tolerance is primarily attributed to the relaxation stage and long-term defect evolution rather than the ballistic stage. These results can provide fundamental insights into irradiation-induced defects evolution in refractory CSAs. [ABSTRACT FROM AUTHOR]

The existence of adversarial image makes us have to doubt the credibility of artificial intelligence system. Attackers can use carefully processed adversarial images to carry out a variety of attacks. Inspired by the theory of image compressed sensing, this paper proposes a new black-box attack, \(\mathcal {N}\text{-HSA}_{LF}\). It uses covariance matrix adaptive evolution strategy (CMA-ES) to learn the distribution of adversarial perturbation in low frequency domain, reducing the dimensionality of solution space. And sep-CMA-ES is used to set the covariance matrix as a diagonal matrix, which further reduces the dimensions that need to be updated for the covariance matrix of multivariate Gaussian distribution learned in attacks, thereby reducing the computational cost of attack. And on this basis, we propose history-driven mean update and current optimal solution-guided improvement strategies to avoid the evolution of distribution to a worse direction. The experimental results show that the proposed \(\mathcal {N}\text{-HSA}_{LF}\) can achieve a higher attack success rate with fewer queries on attacking both CNN-based and transformer-based target models under \(L_2\) -norm and \(L_\infty\) -norm constraints of perturbation. We also conduct an ablation study and the results show that the proposed improved strategies can effectively reduce the number of visits to the target model when making adversarial examples for hard examples. In addition, our attack is able to make the integrated defense strategy of GRIP-GAN and noise-embedded training ineffective to a certain extent. [ABSTRACT FROM AUTHOR]

Background: Long-chain fatty acids (LCFAs) are involved in regulating multiple physiological processes as signalling molecules. Gas chromatography–mass spectrometry (GC–MS) is widely used to quantify LCFAs. However, current quantitative methods for LCFAs using GC–MS have demonstrated complicated issues. Psoriasis is a chronic inflammatory skin disease, and its pathogenesis may be related to the overproduction of interleukin-17A (IL-17A). Clinical efficacy of anti-IL-17A monoclonal antibody (mAb) treatment in psoriasis patients has been demonstrated. Recent studies suggest that LCFAs play varying roles in the pathogenesis of psoriasis. However, more comprehensive research is needed to illuminate the mechanism of LCFAs in psoriasis. Methods: The established in situ derivatization method for analysing LCFAs with a GC–MS platform was utilized to conduct serum lipidomics analysis of healthy volunteers and psoriasis patients receiving pretherapy and posttreatment with of anti-IL-17A mAb. Imiquimod (IMQ)-treated wild type (WT) and T-cell receptor delta chain knock-out (Tcrd−/−) mice were used to investigate the correlation between IL-17A and abnormal changes in LCFAs in psoriasis patients. Results: A rapid and sensitive in situ extraction derivatization method for quantifying LCFAs using GC–MS was established. Serum lipidomic results showed that psoriasis patients had higher levels of saturated fatty acids (SFAs) and ω-6 polyunsaturated fatty acids (PUFAs) but lower levels of monounsaturated fatty acids (MUFAs) and ω-3 PUFAs than healthy individuals, indicating impaired serum LCFA metabolism. Anti-IL-17A mAb treatment affected most of these LCFA changes. Analysis of LCFAs in IMQ-treated mice showed that LCFAs increased in the serum of WT mice, while there were no significant changes in the Tcrd−/− mice. SFAs increased in IMQ-treated WT mice, while MUFAs showed the opposite trend, and PUFAs did not change significantly. Conclusions: This study presented a dependable method for quantifying LCFAs that enhanced sensitivity and reduced analysis time. The lipidomic analysis results showed that anti-IL-17A mAb not only ameliorated skin lesions in psoriasis patients but also affected abnormal LCFAs metabolism. Furthermore, the study indicated a potential correlation between IL-17A and abnormal LCFA metabolism in psoriasis patients, which was supported by the alterations in serum LCFAs observed in IMQ-treated WT and Tcrd−/− mice. [ABSTRACT FROM AUTHOR]

In modern online life, recommender systems can help us filter unimportant information. Researchers of recommendation algorithms usually utilize historical interaction data to mine potential user preferences. However, most existing methods use rating data to mine user interest preferences, ignoring rich textual information such as reviews. Although some researchers have attempted to combine ratings and reviews for recommendation, we believe the following shortcomings still exist. First, existing methods are overly dependent on the accuracy of external sentiment analysis tools. Second, existing methods do not fully utilize the features extracted from reviews. Further, existing methods focus only on the aspects that users like, while ignoring the aspects that users dislike, and they cannot completely model users' true preferences. To address the above issues, in this paper, we propose a recommendation model based on the aspect of the sentiment knowledge graph attention network (ASKAT). We first use the improved aspect-based sentiment analysis algorithm to extract aspectual sentiment features from reviews. Then, to overcome the difficulty in underutilizing the information extracted from the comments, we build aspects of sentiment-enhanced collaborative knowledge mapping. After that, we propose a new graph attention network that uses sentiment-aware attention mechanisms to aggregate neighbour information. Finally, our experimental results on three datasets, Movie, Amazon book, and Yelp, show that our model consistently outperforms the baseline model in two recommendation scenarios, click-through-rate prediction and Top-k recommendation. Compared with other models, the method shows significant improvement in both recommendation accuracy and personalised recommendation effectiveness. [ABSTRACT FROM AUTHOR]

Throughout the COVID-19 pandemic, an unprecedented level of clinical nasal swab data from around the globe has been collected and shared. Positive tests have consistently revealed viral titers spanning six orders of magnitude! An open question is whether such extreme population heterogeneity is unique to SARS-CoV-2 or possibly generic to viral respiratory infections. To probe this question, we turn to the computational modeling of nasal tract infections. Employing a physiologically faithful, spatially resolved, stochastic model of respiratory tract infection, we explore the statistical distribution of human nasal infections in the immediate 48 h of infection. The spread, or heterogeneity, of the distribution derives from variations in factors within the model that are unique to the infected host, infectious variant, and timing of the test. Hypothetical factors include: (1) reported physiological differences between infected individuals (nasal mucus thickness and clearance velocity); (2) differences in the kinetics of infection, replication, and shedding of viral RNA copies arising from the unique interactions between the host and viral variant; and (3) differences in the time between initial cell infection and the clinical test. Since positive clinical tests are often pre-symptomatic and independent of prior infection or vaccination status, in the model we assume immune evasion throughout the immediate 48 h of infection. Model simulations generate the mean statistical outcomes of total shed viral load and infected cells throughout 48 h for each "virtual individual", which we define as each fixed set of model parameters (1) and (2) above. The "virtual population" and the statistical distribution of outcomes over the population are defined by collecting clinically and experimentally guided ranges for the full set of model parameters (1) and (2). This establishes a model-generated "virtual population database" of nasal viral titers throughout the initial 48 h of infection of every individual, which we then compare with clinical swab test data. Support for model efficacy comes from the sampling of infection dynamics over the virtual population database, which reproduces the six-order-of-magnitude clinical population heterogeneity. However, the goal of this study is to answer a deeper biological and clinical question. What is the impact on the dynamics of early nasal infection due to each individual physiological feature or virus–cell kinetic mechanism? To answer this question, global data analysis methods are applied to the virtual population database that sample across the entire database and de-correlate (i.e., isolate) the dynamic infection outcome sensitivities of each model parameter. These methods predict the dominant, indeed exponential, driver of population heterogeneity in dynamic infection outcomes is the latency time of infected cells (from the moment of infection until onset of viral RNA shedding). The shedding rate of the viral RNA of infected cells in the shedding phase is a strong, but not exponential, driver of infection. Furthermore, the unknown timing of the nasal swab test relative to the onset of infection is an equally dominant contributor to extreme population heterogeneity in clinical test data since infectious viral loads grow from undetectable levels to more than six orders of magnitude within 48 h. [ABSTRACT FROM AUTHOR]

Key Clinical Message: There are no reports of application of inotuzumab ozogamicin (InO) for the treatment of MRD in r/r B‐ALL. We firstly report the efficacy of InO for a patient experienced morphological relapse after HSCT and molecular relapse after CART therapy. [ABSTRACT FROM AUTHOR]

Recently, the rotational Doppler effect has attracted broad attention in detecting rotational motion. However, the presently proposed detection techniques based on the rotational Doppler effect are generally configured relying on discrete components in free space, resulting in cumbersome and inflexible systems, which brings challenges to practical applications. In this paper, we demonstrate a fiber-based configuration on rotational Doppler measurements for the detection of a rotational object using an ultra-broadband mode-selective coupler to convert the superposed vortices. Remarkably, the results show the broadband operating range of the fiber-based measurement system intuitively through wavelength scanning. The refinement of rotational Doppler detection techniques is of great significance for lowering the cost, reducing system complexity, improving system integration, and industrial manufacturing. This fiber-based scheme might be a promising candidate for facilitating the rotational Doppler effect applied as novel motion monitoring and sensing equipment in engineering and industry. [ABSTRACT FROM AUTHOR]

This letter published in the Blood Cancer Journal presents a retrospective study comparing the effectiveness of different treatment regimens for acute myeloid leukemia (AML) patients with the RUNX1::RUNX1T1 gene mutation. The study found that venetoclax combined with hypomethylating agents (VEN + HMA) was not more effective than the standard 7 + 3 chemotherapy regimen for these patients. However, the presence of co-mutations in chromatin-cohesin genes was associated with a better response to VEN + HMA. The study highlights the need for further research to determine the best treatment approach for AML patients with the RUNX1::RUNX1T1 mutation. [Extracted from the article]

Most available long-term operation models for hydropower stations use deterministic historical data as inputs but cannot be employed to update the decision scheme in real time according to the actual solar radiation and inflow conditions, resulting in a disconnect between the given plan and actual decision-making process. In this study, a multistage rolling reservoir decision model considering the uncertainties in solar radiation and inflow is proposed to guide the formulation of long-term operational schemes for hydro-PV systems. We adopt the solar radiation and inflow series generated by the scenario tree (ST) method as inputs of the reservoir optimal operation model and use a genetic algorithm (GA) to solve the model. In the solution process, the scheme is adjusted according to the actual solar radiation and inflow conditions. Typical wet, normal, and dry years are analysed. The results illustrate that the model can better inform the design of long-term operational schemes for hydro-PV stations relative to the actual operational scheme and the traditional deterministic model. [ABSTRACT FROM AUTHOR]

Cell-mediated immunity (CMI) plays a key role in the effectiveness of varicella zoster virus (VZV) vaccines, and mRNA vaccines have an innate advantage in inducing CMI. Glycoprotein E (gE) has been used widely as an antigen for VZV vaccines, and carboxyl-terminal mutations of gE are associated with VZV titer and infectivity. In addition, the untranslated regions (UTRs) of mRNA affect the stability and half-life of mRNA in the cell and are crucial for protein expression and antigenic translational efficiency. In this study, three UTRs were designed and connected to the nucleic acid sequence of gE-M, which is double mutated in the extracellular region of gE. Then, mRNA with different nucleic acids was encapsulated in lipid nanoparticles (LNPs), forming three LNP-mRNA VZV vaccines, named gE-M-Z, gE-M-M, and gE-M-P. The immune response elicited by these vaccines in mice was evaluated at intervals of 4 weeks, and the mice were sacrificed 2 weeks after the final immunization. In the results, the gE-M-P group, which retains the nucleic acid sequence of gE-M and is connected to Pfizer/BioNTech's BNT162b2 UTRs, induced the strongest humoral immune response and CMI. Because CMI is crucial for protection against VZV and for the design of VZV vaccines, this study provides a feasible strategy for improving the effectiveness and economy of future VZV vaccines. [ABSTRACT FROM AUTHOR]

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype with a poor prognosis under conventional chemotherapy. Ph-like ALL has a similar gene expression profile to Philadelphia chromosome-positive (Ph+) ALL, but is highly heterogeneous in terms of genomic alterations. Approximately 10–20% of patients with Ph-like ALL harbor ABL class (e.g. ABL1, ABL2, PDGFRB, and CSF1R) rearrangements. Additional genes that form fusion genes with ABL class genes are still being researched. These aberrations result from rearrangements including chromosome translocations or deletions and may be targets of tyrosine kinase inhibitors (TKIs). However, due to the heterogeneity and rarity of each fusion gene in clinical practice, there is limited data on the efficacy of tyrosine kinase inhibitors. Here, we report three cases of Ph-like B-ALL with ABL1 rearrangements treated with the dasatinib backbone for the CNTRL::ABL1, LSM14A::ABL1, and FOXP1::ABL1 fusion genes. All three patients achieved rapid and profound remission with no significant adverse events. Our findings suggest that dasatinib is a potent TKI for the treatment of ABL1-rearranged Ph-like ALL and can be used as a first-line treatment option for such patients. [ABSTRACT FROM AUTHOR]

Photon plays a dominant role as the information carrier in telecom, thanks to the merits of large bandwidth and low energy consumption. Optical encryption has kept attracting intensive attention in the era of frequent information exchange. Multidegrees of light facilitate enhancing the security of data transmission. Here, following the Malus law and the phase encoding rule of the geometric phase, dual-channel intensities and a far-field hologram of the transmitted light are separately programmed. Different quick response codes that link to plaintexts are recorded into two intensity channels. They are further transformed according to the predetermined rule as revealed by the hologram to form the key. The key converts the protected information in a single-pixel imaging process, and generated ciphertexts are inserted into the plaintexts to perform the encryption. The tri-channel liquid crystal device enables simultaneous encryption in two separate routes and significantly improves information security. The design supplies a universal key for data encryption. [ABSTRACT FROM AUTHOR]

Epigenetic alterations frequently participate in the onset of hematological malignancies. Histone deacetylases (HDACs) are essential for regulating gene transcription and various signaling pathways. Targeting HDACs has become a novel treatment option for hematological malignancies. Chidamide is the first oral selective HDAC inhibitor for HDAC1, HDAC2, HDAC3, and HDAC10 and was first approved for the treatment of R/R peripheral T‐cell lymphoma by the China Food and Drug Administration in 2014. Chidamide was also approved under the name Hiyasta (HBI‐8000) in Japan in 2021. In vitro studies revealed that chidamide could inhibit proliferation and induce apoptosis via cell cycle arrest and the regulation of apoptotic proteins. In clinical studies, chidamide was also efficacious in multiple myeloma, acute leukemia and myelodysplastic syndrome. This review includes reported experimental and clinical data on chidamide monotherapy or chidamide treatment in combination with chemotherapy for various hematological malignancies, offering a rationale for the renewed exploration of this drug. [ABSTRACT FROM AUTHOR]

In this study, we propose a MOOC Analytic Statistical Visual model (MOOC-ASV) to explore students' engagement in MOOC courses and predict their performance on the basis of their behaviors logged as big data in MOOC platforms. The model has multifunctions, which performs on visually analyzing learners' data by state-of-the-art techniques. The model presents several visual analyses, which exhibit learners' interaction patterns with course videos and also statistical summaries of associated events for each video. The results showed positive indicators that would enable instructors to identify learners dropping out based on their interactions with videos. The model gives feedback into course instructors and developers to review and modify the course content, especially video content, which ultimately lead to improving the course quality and outcomes. [ABSTRACT FROM AUTHOR]

Background: Tree-structured neural networks have shown promise in extracting lexical representations of sentence syntactic structures, particularly in the detection of event triggers using recursive neural networks. Methods: In this study, we introduce an attention mechanism into Child-Sum Tree-LSTMs for the detection of biomedical event triggers. We incorporate previous researches on assigning attention weights to adjacent nodes and integrate this mechanism into Child-Sum Tree-LSTMs to improve the detection of event trigger words. We also address a limitation of shallow syntactic dependencies in Child-Sum Tree-LSTMs by integrating deep syntactic dependencies to enhance the effect of the attention mechanism. Results: Our proposed model, which integrates an enhanced attention mechanism into Tree-LSTM, shows the best performance for the MLEE and BioNLP'09 datasets. Moreover, our model outperforms almost all complex event categories for the BioNLP'09/11/13 test set. Conclusion: We evaluate the performance of our proposed model with the MLEE and BioNLP datasets and demonstrate the advantage of an enhanced attention mechanism in detecting biomedical event trigger words. [ABSTRACT FROM AUTHOR]

Orbital angular momentum (OAM) has recently attracted increasing interest in optical communications for capacity scaling by OAM mode‐division multiplexing (MDM). OAM (de)multiplexer is crucial to the success of OAM‐MDM communications. Scalable and efficient dense OAM demultiplexing is highly desired, but full of challenges. Here, a quasi‐wavelet conformal mapping method is proposed and demonstrated to implement scalable and efficient dense OAM demultiplexing. The OAM mode is divided at the input plane into multiple concentric rings, which are mapped to multiple tilted plane waves and arranged side by side in a line. The engineered transformed light beams with periodic extension and increased length enable narrow focused spot width, reduced beam overlap, and suppressed demultiplexing crosstalk. The quasi‐wavelet conformal mapping method is compared with conventional log‐polar transformation scheme and hybrid log‐polar and fan‐out technique, and the crosstalk matrix for OAM demultiplexing is measured. Efficient OAM demultiplexing is demonstrated for 15 OAM modes (OAM−7 to OAM+7) with a maximum crosstalk of −12.1 dB in the experiment. Moreover, the method is also applied to system‐level data‐carrying OAM‐MDM communications with favorable performance. The demonstrated quasi‐wavelet conformal mapping method may pave the way for future ultrahigh capacity dense OAM‐MDM communications with a large number of OAM modes. [ABSTRACT FROM AUTHOR]

Yak has evolved specific adaptative mechanisms to high‐altitude environment. Up to date, only a few studies reported the DNA methylation in yak. In the present study, genome‐wide DNA methylome and transcriptome profiles in lung, mammary, and biceps brachii muscle tissues were compared between yak and three cattle breeds (Tibetan cattle, Sanjiang cattle, and Holstein cattle). The association between differentially expressed genes (DEGs) and differentially methylated regions (DMRs) was analyzed, and the biological functions of DEGs potentially driven by DMRs were explored by KEGG enrichment analysis. Finally, we found that yak‐specific DMRs‐driven DEGs were mainly involved in neuromodulation, respiration, lung development, blood pressure regulation, cardiovascular protection, energy metabolism, DNA repair, and immune functions. The higher levels of the key genes associated with these functions were observed in yak than in cattle, suggesting that DNA methylation might regulate these genes. Overall, the present study contributes basic data at the DNA methylation level to further understand the physiological metabolism in yak. Research Highlights: The difference in methylation level were observed in lung and mammary tissues.Yak‐specific DMRs‐driven DEGs were found.The higher levels of the key genes associated with these above functions were observed in yak than in cattle. [ABSTRACT FROM AUTHOR]

A large amount of real-world data suggests that the emergence of variants of concern (VOCs) has brought new challenges to the fight against SARS-CoV-2 because the immune protection elicited by the existing coronavirus disease 2019 (COVID-19) vaccines was weakened. In response to the VOCs, it is necessary to advocate for the administration of booster vaccine doses to extend the effectiveness of vaccines and enhance neutralization titers. In this study, the immune effects of mRNA vaccines based on the WT (prototypic strain) and omicron (B1.1.529) strains for use as booster vaccines were investigated in mice. It was determined that with two-dose inactivated vaccine priming, boosting with mRNA vaccines could elevate IgG titers, enhance cell-mediated immunity, and provide immune protection against the corresponding variants, but cross-protection against distinct strains was inferior. This study comprehensively describes the differences in the mice boosted with mRNA vaccines based on the WT strain and the omicron strain, a harmful VOC that has resulted in a sharp rise in the number of infections, and reveals the most efficacious vaccination strategy against omicron and future SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

In a case study of heavy oil reservoirs in IX6 Well Block, Xinjiang Oilfiled, physical simulation test of multi-media assisted steam flooding was conducted to address such problems as prominent vertical contradiction in the late stage of steam flooding in heavy oil reservoirs and serious steam channeling in the high-permeability layer. Firstly, the gelling performance and viscosity reducing effect of gel were evaluated, and then the combination mode of multi-phase synergistic steam flooding was optimized by full-diameter core. The results show that after the high-permeability layer was plugged by gelling, the subsequently injected multi-phase media effectively entered the low-permeability layer and drove the remaining oil in the low-permeability reservoir. Nitrogen was injected after viscosity reducer injected to effectively enhance the elastic energy and fluidity of crude oil, which was conductive to expanding the sweep volume of steam. The multi-phase synergistic steam flooding development mode of plugging control, viscosity reduction and pressurization is the best combination mode, which can improve the oil recovery rate by 23. 65 percentage points. The study results can provide technical reference for the improved late development effect of steam flooding in heavy oil reservoirs. [ABSTRACT FROM AUTHOR]

Based on the principle of molecular splicing and theory of traditional Chinese medicine pairs, a new multi-active compound (HM475) was synthesized by connecting metformin with honokiol, and its structure was characterized, which not only reduced the toxicity of raw materials, but also maintained the original activity, and had a certain significance in research and innovation. At the same time, quality control and preliminary activity evaluation were carried out, and the effect of HM475 on neuroinflammation was further explored, which provided a new idea for drug development of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the herpes zoster subunit vaccine Shingrix™ performs well in clinical trials. However, the key ingredient in its adjuvant, QS21, is extracted from rare plants in South America, so vaccine production is limited. Compared with subunit vaccines, mRNA vaccines have the advantages of faster production and not requiring adjuvants, but currently, there is no authorized mRNA vaccine for herpes zoster. Therefore, this study focused on herpes zoster subunit and mRNA vaccines. We prepared a herpes zoster mRNA vaccine and compared the effects of vaccine type, immunization route, and adjuvant use on vaccine immunological efficacy. The mRNA vaccine was injected directly into mice via subcutaneous or intramuscular injection. The subunit vaccine was mixed with adjuvants before immunization. The adjuvants include B2Q or alum. B2Q is BW006S + 2395S + QS21. BW006S and 2395S are phosphodiester CpG oligodeoxynucleotides (CpG ODNs). Then, we compared the cell-mediated immunity (CIM) and humoral immunity levels of the different groups of mice. The results showed that the immune responses of mice inoculated with the mRNA vaccine prepared in this study were not significantly different from those of mice inoculated with the protein subunit vaccine supplemented with the B2Q. The mRNA vaccine-induced immune responses following subcutaneous or intramuscular injection, and the different immunization routes did not lead to significant differences in immune response intensity. Similar results were also observed for the protein subunit vaccine adjuvanted with B2Q but not alum. The above results suggest that our experiment can provide a reference for the preparation of mRNA vaccines against herpes zoster and has certain reference significance for the selection of the immunization route; that is, there is no significant difference in the immune response caused by subcutaneous versus an intramuscular injection, so the injection route can be determined according to the actual situation of individuals. [ABSTRACT FROM AUTHOR]

Bentonite cement paste (BCP) is among the grouting materials used widely in large-pore grouting and karst cave treatment. The mechanical properties of bentonite cement paste (BCP) will be improved by additional basalt fibers (BF). In this study, the effects of basalt fiber (BF) contents and their lengths on the rheological and mechanical properties of bentonite cement paste (BCP) have been examined. Yield stress (YS), plastic viscosity (PV), unconfined compressive strength (UCS), and splitting tensile strength (STS) were used to evaluate the rheological and mechanical properties of basalt fiber-reinforced bentonite cement paste (BFBCP). Scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDS) characterize microstructure development. The results indicate that the Bingham model can provide the rheological behavior of basalt fibers and bentonite cement paste (BFBCP). The yield stress (YS) and plastic viscosity (PV) increase as the content and length of basalt fiber (BF) increase. The effect of fiber content on yield stress (YS) and plastic viscosity (PV) is greater than that of fiber length. The addition of basalt fiber (BF) enhanced the unconfined compressive strength (UCS) and splitting tensile strength (STS) of basalt fiber-reinforced bentonite cement paste (BFBCP) at the optimum basalt fiber (BF) content of 0.6%. The optimum basalt fiber (BF) content tends to increase as curing age increases. The basalt fiber length of 9 mm is the most effective for improving unconfined compressive strength (UCS) and splitting tensile strength (STS). The large increments in unconfined compressive strength (UCS) and splitting tensile strength (STS) were 19.17% and 28.21% for the basalt fiber-reinforced bentonite cement paste (BFBCP), with a basalt fiber length of 9 mm and content of 0.6%. Scanning electron microscopy (SEM) shows that the randomly distributed basalt fiber (BF) forms a spatial network structure in basalt fiber-reinforced bentonite cement paste (BFBCP), which composes a stress system under the action of cementation. Basalt fibers (BF) used in crack generation processes slow down the flow through bridging and occur in the substrate to improve the mechanical properties of basalt fiber-reinforced bentonite cement paste (BFBCP). [ABSTRACT FROM AUTHOR]

Pyrogenic dissolved organic matter (pyDOM) is derived from black carbon, which is important in the global carbon cycle and other biogeochemical redox processes. The electron-exchange capacity (EEC) of pyDOM has been characterized in water using mediated chronoamperometry (MCA), which gives precise results under specific operational conditions, but the broader significance of these EECs is less clear. In this study, we described a novel but complementary electrochemical approach to quantify EECs of pyDOM without mediation using square-wave voltammetry (SWV) in dimethyl sulfoxide (DMSO). Using both the SWV and MCA methods, we determined EECs for 10 pyDOMs, 6 natural organic matter (NOM) samples, and 2 model quinones. The two methods gave similar EECs for model quinones, but SWV gave larger EECs than MCA for NOM and pyDOM (by several-fold and 1–2 orders of magnitude, respectively). The differences in the EECs obtained by SWV and MCA likely are due to multiple factors, including the potential range of electrons sampled, kinetics of electron transfer from (macro)molecular structures, and coupling of electron and proton transfer steps. Comparison of the results obtained by these two methods should provide new insights into important environmental processes such as carbon-cycling, wildfire recovery, and contaminant mitigation using carbon-based amendments. [ABSTRACT FROM AUTHOR]

This study proposes a novel physics-informed optimization approach to account for nonlayered soil conditions for the dynamic soil–structure interaction analysis that is critical for structural health monitoring involving soil–structure interaction. This approach can estimate soil properties based on a few measurements and then predict the natural frequency of structures, a key element that has been very often utilized for structural health monitoring and evaluation. A case study for frequency-based bridge scour detection has been presented for the demonstration of this approach, where a bridge pile is partially embedded in complex nonlayered soils. With this case study, we show that the nonlinear frequency–scour depth relationship can be accurately estimated using 2–4 measured data points, which is in favor of situations where conducting a field test is difficult or the demand for conducting field measurements needs to be reduced. The impact of errors resulting from measurement uncertainty on the performance of this approach is found to be insignificant. This physics-informed optimization approach thus can help analyze dynamic responses of engineering structures in complex nonlayered soil conditions involving soil–structure interaction. [ABSTRACT FROM AUTHOR]

Background: Classic (static) Roentgen stereophotogrammetric analysis (RSA) is the current gold standard to assess, in vivo, the migration of total joint arthroplasty components. To prevent potential patient motion artifacts during the acquisition of paired radiostereometric images, images must be taken by simultaneously firing both X-ray tubes. However, the influence of nonsynchronized RSA paired images or patient motion artifacts on the precision of RSA and the assessment of implant migration is not well understood.Questions/purposes: We assessed (1) the effect of possible patient motion on the precision of RSA and (2) apparent differences in implant migration among axes (in-plane and out-of-plane translations and in-plane and out-of-plane rotations) of possible motion artifacts.Methods: Radiographs of two tibial knee arthroplasty components, each fixed in two bone-implant models as a customized phantom, were taken in a uniplanar measurement setup. We evaluated both model-based (implant models from reversed engineering) and marker-based (additional attached implant markers) RSA approaches. Between the simulated reference and follow-up examinations, we used one of the bone-implant models to simulate patient motion and the other to simulate no patient motion in parallel. Two defined protocols were followed for each of the bone-implant models: no-motion and simulated motion protocols. RSA image pairs were analyzed using a model-based RSA software package (MBRSA 4.1, RSAcore). Precision was calculated through repeat examinations, and migration of the two components was assessed for comparison of the components with each other. Measurements were taken along the medial-lateral and posterior-anterior axes for translations and around the cranial-caudal axis for rotations. The maximum total point motion was measured for comparison between the two components.Results: The effect of simulated patient motion was generally small, except in the cranial-caudal axis, but the induced imprecision associated with motion was larger in model-based RSA than it was in marker-based RSA. The mean ± standard deviation values of precision in model-based RSA were 0.035 ± 0.015 mm, 0.045 ± 0.014 mm, and 0.049 ± 0.036 mm greater than those in marker-based RSA, in accordance with the simulated motion protocol in translations along the medial-lateral axis (0.018 ± 0.004 mm; p = 0.01), along the posterior-anterior axis (0.018 ± 0.007 mm; p = 0.003), and rotations around the cranial-caudal axis (0.017 ± 0.006 mm; p = 0.02). Apparent differences in implant migration were the greatest for the maximum total point motion. The maximum total point motion increased from 0.038 ± 0.007 mm for the no-motion protocol to 1.684 ± 0.038 mm (p < 0.001) for the simulated motion protocol in marker-based RSA, and from 0.101 ± 0.027 mm for the no-motion protocol to 1.973 ± 0.442 mm (p < 0.001) for the simulated motion protocol in model-based RSA, and was the worst-case scenario regarding patient motion artifacts.Conclusion: Patient motion exceeding 1 mm or 1° on nonsynchronized RSA images affects measurement errors regarding the detection of migration of a tibial component. In clinical RSA studies, the effect of patient motion on the assessment of implant migration should be of particular concern, even if clinical RSA systems have acceptable precision. Specially trained radiographers are crucial for correctly acquiring radiographs, especially when simultaneous radiography exposures are not electronically automated. In general, RSA requires synchronized image acquisition, and this should be the state-of-the-art.Clinical Relevance: In clinical RSA studies, precision assessed by repeat examinations may not be reliable using the current standards that are widely used in radiology departments. When assessing implant migration for reliability, comparison of the maximum total point motion between the tested (simulated motion) implant and baseline (no-motion) implant, as in this study, is advocated because of the accurate detection of patient motion artifacts. [ABSTRACT FROM AUTHOR]

Hydraulic fracturing is the most widely used primary method for the stimulation of unconventional oil and gas resources. While knowledge of hydraulic fracture parameters is critical to reservoir productivity, predicting the fracture initiation is important for determining the complexity of the fracture network. Subcritical crack growth in reservoir rock plays an important role in forming fracture networks, but the understanding of the influence of fracturing conditions on subcritical crack growth is still lacking. In this paper, the subcritical crack growth behavior of sandstone and shale under ambient air, deionized (DI) water, and slick‐water conditions is studied. X‐ray diffraction analysis is done on the rock samples to determine their mineralogical composition, while tensile strength is measured by the Brazilian test. Then in Load Relaxation mode, a Double‐Torsion test (DT) is carried out under different conditions to study the subcritical crack growth of the samples. To further verify the influence of clay‐rich minerals, a similar analysis is performed on clay‐free granitic rock samples. The results of the tensile strength test and DT test demonstrate that the presence of clay minerals is the main reason for the difference in the subcritical crack growth behavior of shale and sandstone samples. DI water seems to better improve the subcritical crack growth compared with other test conditions. The value of the Subcritical Index (n) is smaller in a slick‐water environment than that in a DI water environment, revealing that slick water can better promote complex fracture propagation. [ABSTRACT FROM AUTHOR]

Philadelphia chromosome‐positive acute myeloid leukemia (Ph + AML) is a rare type of AML with a low survival rate and poor prognosis. We first report a Ph + AML patient who remained in long‐term remission after the combination of flumatinib and venetoclax, which could provide corresponding treatment ideas for clinical practice. The figure shows the treatment process of the patient and the dynamic changes in blood cell count during venetoclax and flumatinib. The BCR::ABL1 transcript was negative after two courses of the combination of venetoclax anf flumatinib. No serious adverse events occurred during the treatment, although hematological toxicity was observed. [ABSTRACT FROM AUTHOR]

The complete remission (CR) rate and overall survival (OS) of relapsed/refractory (R/R) B-cell acute lymphoblastic leukaemia (B-ALL) are not satisfactory. The available salvage regimens include standard chemotherapy, inotuzumab ozogamicin, blinatumomab and cluster of differentiation (CD)19 chimeric antigen receptor T cells (CAR T), and the NCCN guidelines recommend all of these therapies with no preference. Dual CD19/CD22 CAR T-cells have emerged as new treatments and have shown some efficacy, with high CR rates and preventing CD19-negative relapse. However, direct comparisons of the CR rate and long-term survival among the different salvage therapies are lacking. Databases including PubMed, Embase, Web of Science and Cochrane were searched from inception to January 31, 2022, for relevant studies. The outcomes of interest were complete remission/complete remission with incomplete haematologic recovery (CR/CRi) rates and 1-year overall survival (OS) rates. Odds ratios (ORs) were generated for binary outcomes, and the mean difference (MD) was generated for consecutive outcomes by network meta-analysis. CD19 CAR T-cells demonstrated a significantly better effect in improving the CR/CRi rate than blinatumomab (OR = 8.32, 95% CI: 1.18 to 58.44) and chemotherapy (OR = 16.4, 95% CI: 2.76 to 97.45). In terms of OS, CD19 CAR T-cells and dual CD19/CD22 CAR T-cells both had a higher 1-year OS rate than blinatumomab, inotuzumab ozogamicin and chemotherapy. There was no significant difference between CD19 CAR T-cells and dual CD19/CD22 CAR T-cells in terms of 1-year OS and CR/CRi rates. CD19 CAR T-cells are effective in inducing CR, and CD19 CAR T-cells and dual CD19/CD22 CAR T-cells show benefits for overall survival. More high-quality randomized controlled trials and longer follow-ups are needed to confirm and update the results of this analysis in the future. [ABSTRACT FROM AUTHOR]

Background: The yak is the most important livestock in the Qinghai-Tibet Plateau, and body weight directly affects the economic values of yak. Up to date, the genome-wide profiling of single-nucleotide polymorphisms (SNPs) associating with body weight has not been reported in yak. In the present study, the SNPs in 480 yaks from three breeds were analyzed using the commercial high-density (600 K) yak SNP chips. Results: The results identified 12 and 4 SNPs potentially associated with body weight in male and female yaks, respectively. Among them, 9 and 2 SNPs showed significant difference in yak body weight between different genotypes at each locus in male and female yaks, respectively. Further exploration found 33 coding genes within the 100 kbp upstream or downstream to the SNP loci, which might be potentially affected by the variation of SNPs. Among them, G protein-coupled receptor kinase 4 (GRK4) might be potentially affected by the SNP AX-174555047, which has been reported to affect the functioning of two body-weight associated hormones (parathyroid hormone, PTH, and adrenomedullin, ADM). Determination of PTH and ADM levels in yak revealed positive relationship between PTH level and body weight, negative relationship between ADM level and body weight along with the variation of AX-174555047 mutation. Conclusions: These results suggested that the SNP AX-174555047 might potentially affect body weight through mediating GRK4 expression and then PTH and ADM functioning. Thus, the SNP AX-174555047 might be used as a biomarker for molecular breeding of yak. More investigations are required to validate this point. [ABSTRACT FROM AUTHOR]

Hydraulic fracture (HF) propagation behavior is significant when building an enhanced geothermal system for hot dry rock (HDR) and evaluating the simulated reservoir volume (SRV) for shale gas reservoirs. The HF propagation behaviors are closely related to geologically structural discontinuities (SDs), which differ significantly between HDR and shale. Granite, one of the most common HDRs, mainly possesses natural fractures (NFs), quartz veins (QVs), and lithological interfaces (LIs). The SDs in the shale are mainly bedding planes (BPs) and NFs. According to the physical and mechanical property differences regarding the rock matrix, SDs can be divided into discontinuous planes and discontinuous rocks. The physical simulation experiment of hydraulic fracturing is an effective way to assess the geometry and propagation behaviors of HFs. However, the HF propagation behaviors are not generally well understood, especially the influence of multiple SDs on the HF geometry. To clarify this further, a comparative study of hydraulic fracturing on granite and shale was conducted to investigate the intersection mechanism between HFs and different SDs. The results show that HF propagation behaviors are characterized by six basic patterns: along the SD, crossing without dilation, crossing and dilation, captured by the SD, branching, and deflection. The intersection behaviors are closely associated with the cementing strength of the SD and differences in the fracture toughness of discontinuous rocks. Moreover, the fluctuation degree of the pressure-time curve and complexity of the HFs seem positively correlated. HF propagation in a rock matrix or cross interference with multiple SDs would induce a higher injection pressure and frequent fluctuations. The acoustic emission (AE) energy in granite was higher than that observed in shale. In addition, the generation of new HFs in the rock matrix can induce more AE events than those created simply by propagating along SDs. Experimental investigations can provide a theoretical basis to optimize the engineering parameters of field fracturing. [ABSTRACT FROM AUTHOR]

Motivation In multi-cohort machine learning studies, it is critical to differentiate between effects that are reproducible across cohorts and those that are cohort-specific. Multi-task learning (MTL) is a machine learning approach that facilitates this differentiation through the simultaneous learning of prediction tasks across cohorts. Since multi-cohort data can often not be combined into a single storage solution, there would be the substantial utility of an MTL application for geographically distributed data sources. Results Here, we describe the development of 'dsMTL', a computational framework for privacy-preserving, distributed multi-task machine learning that includes three supervised and one unsupervised algorithms. First, we derive the theoretical properties of these methods and the relevant machine learning workflows to ensure the validity of the software implementation. Second, we implement dsMTL as a library for the R programming language, building on the DataSHIELD platform that supports the federated analysis of sensitive individual-level data. Third, we demonstrate the applicability of dsMTL for comorbidity modeling in distributed data. We show that comorbidity modeling using dsMTL outperformed conventional, federated machine learning, as well as the aggregation of multiple models built on the distributed datasets individually. The application of dsMTL was computationally efficient and highly scalable when applied to moderate-size (n  < 500), real expression data given the actual network latency. Availability and implementation dsMTL is freely available at https://github.com/transbioZI/dsMTLBase (server-side package) and https://github.com/transbioZI/dsMTLClient (client-side package). Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Most of the freshwater in the aquifers in the Ningbo Basin has been replaced or mixed with seawater due to transgressions during the Late Pleistocene and Holocene. Only one freshwater lens has been preserved in the central area of the basin. Scholars believe that the deep confined freshwater lens in the Ningbo Basin is connate. However, there is a lack of research focusing on this topic and the evidence is insufficient. The data obtained from monitoring wells suggest that groundwater has been exploited until now. The evolution of the tectonic stress field and fault data for the Ningbo Basin indicate that the concealed NE- and NW-trending faults are likely water-conducting. Thus, the following hypothesis was put forward: the deep confined aquifers were recharged upward by the fissure water of the concealed faults. A series of tests and analyses of hydrochemical ions and various isotopes of the deep confined water were carried out, and two sets of hydrogeochemical and isotopic data obtained in November 2017 and May 2018 were compared. The 3H activity indicates notable recharge of the aquifers with modern water. The significant correlation between the 14C age and the 222Rn activity indicates rapid groundwater replacement in several sampling wells. The location of these sampling wells is related closely to the concealed faults. Thus, the hypothesis can be confirmed; the deep confined aquifers were recharged by modern water from the bottom and the concealed faults provided the access. [ABSTRACT FROM AUTHOR]