SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.

Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.

Deep integration of metabolome and transcriptome characterizes alkaloid metabolism in Houttuynia cordata.

Alkaloids are the main medicinal components in Houttuynia cordata. In this study, two accessions 6# and 7# of H. cordata underwent thorough metabolomic analyses to identify and quantify alkaloid phytometabolites. It turned out that the alkaloid types were largely similar between 6# and 7#, and the identified 81 alkaloids could be divided into nine structural classes. However, the content of alkaloids in the two accessions was quite different. According to transcriptome data, a total of 114 differentially expressed genes related to alkaloid metabolism were screened. The alkaloid synthesis pathway of the two varieties was mainly different in the isoquinoline alkaloid biosynthesis and indole alkaloid biosynthesis; four genes A22110063c_transcript_59323, A22110063c_transcript_60118, A22110063c_transcript_51672 and A22110063c_transcript_48784 were highly expressed in 7#, which could be key candidate genes of alkaloid metabolism and warrant further analysis. These results provide a reference for the medicinal application of H. cordata and breeding alkaloid rich varieties.

Orthogonally woven 3D nanofiber scaffolds promote rapid soft tissue regeneration by enhancing bidirectional cell migration.

Repairing large-area soft tissue defects caused by traumas is a major surgical challenge. Developing multifunctional scaffolds with suitable scalability and favorable cellular response is crucial for soft tissue regeneration. In this study, we developed an orthogonally woven three-dimensional (3D) nanofiber scaffold combining electrospinning, weaving, and modified gas-foaming technology. The developed orthogonally woven 3D nanofiber scaffold had a modular design and controlled fiber alignment. In vitro, the orthogonally woven 3D nanofiber scaffold exhibited adjustable mechanical properties, good cell compatibility, and easy drug loading. In vivo, for one thing, the implantation of an orthogonally woven 3D nanofiber scaffold in a full abdominal wall defect model demonstrated that extensive granulation tissue formation with enough mechanical strength could promote recovery of abdominal wall defects while reducing intestinal adhesion. Another result of diabetic wound repair experiments suggested that orthogonally woven 3D nanofiber scaffolds had a higher wound healing ratio, granulation tissue formation, collagen deposition, and re-epithelialization. Taken together, this novel orthogonally woven 3D nanofiber scaffold may provide a promising and effective approach for optimal soft tissue regeneration.

TCAF1 promotes TRPV2-mediated Ca2+ release in response to cytosolic DNA to protect stressed replication forks.

The protection of the replication fork structure under stress conditions is essential for genome maintenance and cancer prevention. A key signaling pathway for fork protection involves TRPV2-mediated Ca2+ release from the ER, which is triggered after the generation of cytosolic DNA and the activation of cGAS/STING. This results in CaMKK2/AMPK activation and subsequent Exo1 phosphorylation, which prevent aberrant fork processing, thereby ensuring genome stability. However, it remains poorly understood how the TRPV2 channel is activated by the presence of cytosolic DNA. Here, through a genome-wide CRISPR-based screen, we identify TRPM8 channel-associated factor 1 (TCAF1) as a key factor promoting TRPV2-mediated Ca2+ release under replication stress or other conditions that activate cGAS/STING. Mechanistically, TCAF1 assists Ca2+ release by facilitating the dissociation of STING from TRPV2, thereby relieving TRPV2 repression. Consistent with this function, TCAF1 is required for fork protection, chromosomal stability, and cell survival after replication stress.

Advancements in Dermatological Applications of Curcumin: Clinical Efficacy and Mechanistic Insights in the Management of Skin Disorders.

Curcumin, derived from Curcuma longa (turmeric), exhibits significant potential in dermatology, addressing conditions like atopic dermatitis, psoriasis, chronic wounds, skin cancer, and infections through its anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. This review synthesizes evidence on curcumin's mechanisms, including modulation of immune responses and promotion of wound healing, showcasing its efficacy in reducing inflammation, cytokine levels, and enhancing skin barrier functions. Studies highlight curcumin's ability to selectively target tumor cells, suggesting a multifaceted approach to cancer therapy with minimal side effects. Despite promising therapeutic benefits, challenges remain in bioavailability, potency, and targeted delivery, underscoring the need for further research to optimize dosages, delivery methods, and assess long-term safety. The integration of curcumin into dermatological practice requires a balanced consideration of evidence-based efficacy and safety. Curcumin's comprehensive utility in dermatology, coupled with the necessity for advanced scientific exploration, emphasizes the importance of combining traditional knowledge with contemporary research to improve patient care in dermatology. This approach could significantly enhance outcomes for individuals with skin-related conditions, marking curcumin as a versatile and promising agent in the field.

An unsupervised water quality anomaly detection method based on a combination of time-frequency analysis and clustering.

Anomalies in water quality, which frequently arise due to pollution, constitute a substantial menace to human health. The preservation of public welfare critically entails the timely recognition of abnormal water quality. Conventional techniques for detecting water quality anomalies face obstacles such as the necessity of expert knowledge, limited accuracy in detection, and delays in identification. In this paper, we proposed an original unsupervised technique for identifying water quality anomalies combined with time-frequency analysis and clustering (TCAD). We chose time-frequency analysis because it effectively evaluates water quality changes, generating distinct multi-band signals that reflect different aspects of water quality dynamics. We also proposed a clustering technique which can identify water quality markers and amalgamate data from multi-band signals for accurate anomaly detection. We seek to clarify the reasoning behind our methodology by portraying how time-frequency analysis and clustering address the deficiencies of conventional methods. Our experiments evaluated various indicators of water quality, and the effectiveness of our proposed approach was supported by comparative analyses with commonly used models for detecting anomalies in water quality.

Soluble signal inhibitory receptor on leukocytes-1 reflects disease activity and assists diagnosis of patients with rheumatoid arthritis.

BACKGROUND: SIRL-1, an immunosuppressive receptor encoded by the VSTM1 gene, has recently been linked to rheumatoid arthritis (RA) due to its association with activated polymorphonuclear neutrophils (PMNs). Considering that the activated PMNs play a crucial role in the pathogenesis of rheumatoid arthritis (RA), we aimed to measure the levels of soluble SIRL-1, investigating whether they add value to RA in the clinical diagnosis. METHODS: Utilizing an enzyme-linked immunosorbent assay, the concentration of sSIRL-1 was measured in serum samples from cohort 1 diagnosed with RA (n = 96), gout (n = 54), osteoarthritis (n = 47), healthy controls (n = 86) and synovial fluid samples from OA (n = 8) and RA (n = 8) patients, respectively. Additionally, an external validation in cohort 2 (n = 156) comprising various inflammatory diseases was employed. RESULTS: The study revealed a distinctive upregulation of sSIRL-1 in the serum of RA compared to HC and other arthralgia diseases (p < 0.0001), which also displayed a significant elevation in synovial fluid from RA compared to OA (p < 0.05). Notably, sSIRL-1 levels exhibited a significant decrease in patients who achieved disease remission (p < 0.05). Furthermore, the diagnostic accuracy of RA was enhanced when sSIRL-1 was combined with anti-CCP and RF, yielding an impressive AUC value of 0.950. CONCLUSION: The expression pattern of sSIRL-1 in RA, coupled with its correlation with disease activity, underscores its potential clinical utility for both diagnosis and disease monitoring in RA patients. This study offers valuable insights into the evolving diagnostic landscape of RA.

Anti-Inflammatory Peptide-Conjugated Silk Fibroin/Cryogel Hybrid Dual Fiber Scaffold with Hierarchical Structure Promotes Healing of Chronic Wounds.

Chronic wounds resulting from diabetes, pressure, radiation therapy, and other factors continue to pose significant challenges in wound healing. To address this, this study introduces a novel hybrid fibroin fibrous scaffold (FFS) comprising randomly arranged fibroin fibers and vertically aligned cryogel fibers (CFs). The fibroin scaffold is efficiently degummed at room temperature and simultaneously formed a porous structure. The aligned CFs are produced via directional freeze-drying, achieved by controlling solution concentration and freezing polymerization temperature. The incorporation of aligned CFs into the expanded fibroin fiber scaffold leads to enhanced cell infiltration both in vitro and in vivo, further elevating the hybrid scaffold's tissue compatibility. The anti-inflammatory peptide 1 (AP-1) is also conjugated to the hybrid fibrous scaffold, effectively transforming the inflammatory status of chronic wounds from pro-inflammatory to pro-reparative. Consequently, the FFS-AP1+CF group demonstrates superior granulation tissue formation, angiogenesis, collagen deposition, and re-epithelialization during the proliferative phase compared to the commercial product PELNAC. Moreover, the FFS-AP1+CF group displays epidermis thickness, number of regenerated hair follicles, and collagen density closer to normal skin tissue. These findings highlight the potential of random fibroin fibers/aligned CFs hybrid fibrous scaffold as a promising approach for skin tissue filling and tissue regeneration.

Effects of ultrasound-assisted intermittent tumbling on the quality of cooked ham through modifying muscle structure and protein extraction.

BACKGROUND: Tumbling treatment is widely used in the production of cooked ham. However, traditional intermittent tumbling (IT) treatment is time-consuming. To enhance the tumbling efficiency, high-intensity ultrasound was used to assist IT treatment (UIT). RESULTS: UIT treatment reduced the tumbling time and significantly improved the water holding capacity, tenderness, sliceability and texture of cooked ham compared to IT treatment. Furthermore, more violent destruction of meat tissue was exhibited in the UIT treatment. This change facilitated extraction of more salt-soluble protein, which in turn welded meat pieces tightly and improved the quality of the cooked ham. CONCLUSION: UIT treatment could accelerate the tumbling process and enhance the quality of cooked ham. These results may provide guidance on effective strategies for a high-quality meat production process. © 2023 Society of Chemical Industry.

Additively Manufactured Flexible Liquid Metal-Coated Self-Powered Magnetoelectric Sensors with High Design Freedom.

Although additive manufacturing enables controllable structural design and customized performance for magnetoelectric sensors, their design and fabrication still require careful matching of the size and modulus between the magnetic and conductive components. Achieving magnetoelectric integration remains challenging, and the rigid coils limit the flexibility of the sensors. To overcome these obstacles, this study proposes a composite process combining selective laser sintering (SLS) and 3D transfer printing for fabricating flexible liquid metal-coated magnetoelectric sensors. The liquid metal forms a conformal conductive network on the SLS-printed magnetic lattice structure. Deformation of the structure alters the magnetic flux passing through it, thereby generating voltage. A reverse model segmentation and summation method is established to calculate the theoretical magnetic flux. The impact of the volume fraction, unit size, and height of the sensors on the voltage is studied, and optimization of these factors yields a maximum voltage of 45.6 µV. The sensor has excellent sensing performance with a sensitivity of 10.9 kPa-1 and a minimum detection pressure of 0.1 kPa. The voltage can be generated through various external forces. This work presents a significant advancement in fabricating liquid metal-based magnetoelectric sensors by improving their structural flexibility, magnetoelectric integration, and design freedom.

Co-Mn-Fe spinel-carbon composite catalysts enhanced persulfate activation for degradation of neonicotinoid insecticides: (Non) radical path identification, degradation pathway and toxicity analysis.

The extensive utilization of neonicotinoid insecticides (NNIs) in agricultural practices ultimately poses a significant threat to both the environment and human health. This work focuses on the efficient degradation and detoxification of the representative NNI, thiamethoxam (THX), and explores the underlying mechanism using a Co-Fe-Mn mixed spinel doped carbon composite catalyst activated persulfate. The findings demonstrate that the composite effectively degrades THX, achieving a degradation rate of 95% in 30 mins, while requiring only a fraction (one-sixteenth) of the oxidant dosage compared to pure carbon. The study aimed to examine the negative impact of reactive halogens on reactive oxygen species within a saline environment. The degradation byproducts were linked to the presence of two common electron-withdrawing groups, namely halogens and nitro in the THX molecule. It was hypothesized that the degradation process was primarily influenced by C-N bond breaking and hydroxylation occurring between the diazine oxide and 2-chlorothiazole rings. Consequently, dehalogenation and carbonylation processes facilitated the elimination of halogenated components and pharmacophores from the THX, leading to detoxification. In addition to the identified free radical pathway including SO4•-, •OH and O2•- contributed to THX degradation, the participation of non-radical pathways (1O2 and electron transfer) were also confirmed. The efficacy of detoxification was further validated through toxicity assessment, employing quantitative conformation relationship prediction and microbial culture utilizing Bacillus subtilis.

Does air pollution exposure affect semen quality? Evidence from a systematic review and meta-analysis of 93,996 Chinese men.

Background: Air pollution may impair male fertility, but it remains controversial whether air pollution affects semen quality until now. Objectives: We undertake a meta-analysis to explore potential impacts of six pollutants exposure during the entire window (0-90 days prior to ejaculation) and critical windows (0-9, 10-14, and 70-90 days prior to ejaculation) on semen quality. Methods: Seven databases were retrieved for original studies on the effects of six pollutants exposure for 90 days prior to ejaculation on semen quality. The search process does not limit the language and search date. We only included original studies that reported regression coefficients (ß) with 95% confidence intervals (CIs). The ß and 95% CIs were pooled using the DerSimonian-Laird random effect models. Results: PM2.5 exposure was related with decreased total sperm number (10-14 lag days) and total motility (10-14, 70-90, and 0-90 lag days). PM10 exposure was related with reduced total sperm number (70-90 and 0-90 lag days) and total motility (0-90 lag days). NO2 exposure was related with reduced total sperm number (70-90 and 0-90 lag days). SO2 exposure was related with declined total motility (0-9, 10-14, 0-90 lag days) and total sperm number (0-90 lag days). Conclusion: Air pollution affects semen quality making it necessary to limit exposure to air pollution for Chinese men. When implementing protective measures, it is necessary to consider the key period of sperm development.

Single-cell massively-parallel multiplexed microbial sequencing (M3-seq) identifies rare bacterial populations and profiles phage infection.

Bacterial populations are highly adaptive. They can respond to stress and survive in shifting environments. How the behaviours of individual bacteria vary during stress, however, is poorly understood. To identify and characterize rare bacterial subpopulations, technologies for single-cell transcriptional profiling have been developed. Existing approaches show some degree of limitation, for example, in terms of number of cells or transcripts that can be profiled. Due in part to these limitations, few conditions have been studied with these tools. Here we develop massively-parallel, multiplexed, microbial sequencing (M3-seq)-a single-cell RNA-sequencing platform for bacteria that pairs combinatorial cell indexing with post hoc rRNA depletion. We show that M3-seq can profile bacterial cells from different species under a range of conditions in single experiments. We then apply M3-seq to hundreds of thousands of cells, revealing rare populations and insights into bet-hedging associated with stress responses and characterizing phage infection.

Bi-functional biochar-g-C3N4-MgO composites for simultaneously minimizing pollution：Photocatalytic degradation of pesticide and phosphorus recovery as slow-release fertilizer.

Significant progress has been made in the development of phosphorus recovery adsorbents and photocatalysts for degradation of pesticides. However, the bifunctional materials for phosphorus recovery and photocatalytic degradation of pesticides have not been designed, and the mechanism of the interaction between photocatalysis and P adsorption remains unexplored. Herein, we develop biochar-g-C3N4-MgO composites (BC-g-C3N4-MgO) with bi-function application to minimize water toxicity and eutrophication. The results show phosphorus adsorption capacity of the BC-g-C3N4-MgO composite reaches 111.0 mg·g-1, and its degradation ratio of dinotefuran reaches 80.1% within 260 min. The mechanism studies show that MgO can play variety roles in BC-g-C3N4-MgO composite, in which can improve the adsorption capacity of phosphorus, enhance the utilization efficiency of visible light and the separation efficiency of photoinduced electron-hole pairs. The biochar existed in BC-g-C3N4-MgO serves as charge transporter with a good conductivity, which promotes the fluent transfer of photo-generated charge carriers. The ESR indicates that both •O2- and •OH generated from BC-g-C3N4-MgO are responsible for dinotefuran degradation. Finally, pot experiments reveal that P laden BC-g-C3N4-MgO promotes the growth of pepper seedlings with high P utilization efficiency of 49.27%.

Does exposure to air pollution during different time windows affect pregnancy outcomes of in vitro fertilization treatment? A systematic review and meta-analysis.

Few researches have examined the impact of air pollution exposure during various time windows on clinical outcomes in women receiving in vitro fertilization (IVF) therapy, and the findings of studies have been conflicting. We investigated the effects of six air pollutants exposure during different time windows (period 1, 85 days before egg retrieval to the beginning of gonadotropin; period 2, the beginning of gonadotropin to egg collection; period 3, egg collection to embryo transfer; period 4, embryo transfer to serum hCG measurement; period 5, serum hCG measurement to transvaginal ultrasonography; period 6, 85 days before egg retrieval to hCG measurement; period 7, 85 days before egg retrieval to transvaginal ultrasonography) on clinical outcomes of IVF therapy. A total of seven databases were searched. NO2 (period 6), SO2 (period 2, 3, and 7), CO (period 1, 2 and 7) exposure were linked to lower likelihoods of clinical pregnancy. PM2.5 (period 1), PM10 (period 1), SO2 (period 1, 2, 3, 4, and 6), NO2 (period 1) were linked to lower likelihoods of biochemical pregnancy. PM2.5 (period 1), SO2 (period 2 and 4) and CO (period 2) were linked to reduced probabilities of live birth. Our results implied that period 1 might be the most sensitive exposure window. Air pollution exposure is linked to reduced probabilities of clinical pregnancy, biochemical pregnancy, and live birth. Therefore, preventive measures to limit air pollution exposure should be started at least three months in advance of IVF therapy to improve pregnancy outcomes.

Targeting the endocannabinoid system: Structural determinants and molecular mechanism of allosteric modulation.

Although drugs targeting the orthosteric binding site of cannabinoid receptors (CBRs) have several therapeutic effects on human physiological and pathological conditions, they can also cause serious adverse effects. Only a few orthosteric ligands have successfully passed clinical trials. Recently, allosteric modulation has become a novel option for drug discovery, with fewer adverse effects and the potential to avoid drug overdose. In this review, we highlight novel findings related to the drug discovery of allosteric modulators (AMs) targeting CBRs. We summarize newly synthesized AMs and the reported/predicted allosteric binding sites. We also discuss the structural determinants of the AMs binding as well as the molecular mechanism of CBR allostery.

Weakly acidic microenvironment of the wound bed boosting the efficacy of acidic fibroblast growth factor to promote skin regeneration.

The pH value within the wound microenvironment influences indirectly and directly all biochemical reactions taking place in the process of skin wound healing. Currently, it is generally believed that a low pH value, such as it is found on normal skin, is favorable for wound regeneration, while some investigations have shown that in fact alkaline microenvironments are required for some healing processes. The role of growth factors in promoting wound healing requires a specific microenvironment. In wound microenvironments of different pH, growth factors with different isoelectric points may have different effects. To explore whether the application of FGF with different isoelectric points in wounds with different pH values interferes with the healing process to different degrees, GelMA hydrogels with different pH values were prepared to maintain the wounds microenvironment with the same pH values, in which aFGF and bFGF were loaded as well. The results show that GelMA hydrogels of different pH values maintained the same pH of the wound microenvironment sustainably on the 4th day. Moreover, aFGF and bFGF promoted skin wound healing to varying degrees in different pH wound microenvironments. In particular, aFGF significantly promoted wound re-epithelialization in a weak acidic microenvironment, while bFGF promoted collagen synthesis and deposition in the early stage of weak acid wounds. In addition, aFGF plays a superior role in inhibiting inflammation in weak acidic wounds.

Molecular Modeling Study of a Receptor-Orthosteric Ligand-Allosteric Modulator Signaling Complex.

Allosteric modulators (AMs) are considered as a perpetual hotspot in research for their higher selectivity and various effects on orthosteric ligands (OL). They are classified in terms of their functionalities as positive, negative, or silent allosteric modulators (PAM, NAM, or SAM, respectively). In the present work, 11 pairs of three-dimensional (3D) structures of receptor-orthosteric ligand and receptor-orthosteric ligand-allosteric modulator complexes have been collected for the studies, including three different systems: GPCR, enzyme, and ion channel. Molecular dynamics (MD) simulations are applied to quantify the dynamic interactions in both the orthosteric and allosteric binding pockets and the structural fluctuation of the involved proteins. Our results showed that MD simulations of moderately large molecules or peptides undergo insignificant changes compared to crystal structure results. Furthermore, we also studied the conformational changes of receptors that bound with PAM and NAM, as well as the different allosteric binding sites in a receptor. There should be no preference for the position of the allosteric binding pocket after comparing the allosteric binding pockets of these three systems. Finally, we aligned four distinct ß2 adrenoceptor structures and three N-methyl-d-aspartate receptor (NMDAR) structures to investigate conformational changes. In the ß2 adrenoceptor systems, the aligned results revealed that transmembrane (TM) helices 1, 5, and 6 gradually increased outward movement from an enhanced inactive state to an improved active state. TM6 endured the most significant conformational changes (around 11 Å). For NMDAR, the bottom section of NMDAR's ligand-binding domain (LBD) experienced an upward and outward shift during the gradually activating process. In conclusion, our research provides insight into receptor-orthosteric ligand-allosteric modulator studies and the design and development of allosteric modulator drugs using MD simulation.

Health risk assessment of volatile organic compounds (VOCs) emitted from landfill working surface via dispersion simulation enhanced by probability analysis.

The assessment of the health risks of volatile organic compounds (VOCs) emitted from landfills via dispersion model is crucial but also challenging because of remarkable variations in their emissions and meteorological conditions. This study used a probabilistic approach for the assessment of the health risks of typical VOCs by combining artificial neural network models for emission rates and a numerical dispersion model enhanced by probability analysis. A total of 8753 rounds of simulation were performed with distributions of waste compositions and the valid hourly meteorological conditions for 1 year. The concentration distributions and ranges of the typical health-risky VOCs after dispersion were analyzed with 95% probability. The individual and cumulative non-carcinogenic risks of the typical VOCs were acceptable with all values less than 1 in the whole study domain. For individual carcinogenic risks, only ethylbenzene, benzene, chloroform, and 1, 2-dichloroethane at extreme concentrations showed minor or moderate risks with a probability of 0.1%-1% and an impact distance of 650-3000 m at specific directions. The cumulative carcinogenic risks were also acceptable at 95% probability in the whole study domain, but exceeded 1 × 10-6 or even 1 × 10-4 at some extreme conditions, especially within the landfill area. The vertical patterns of the health risks with height initially increased, and then decreased rapidly, and the peak values were observed around the height of the emission source. The dispersion simulation and health risk assessment of the typical health-risky VOCs enhanced by Monte Carlo can accurately reflect their probabilistic dispersion patterns and health risks to surrounding residents from both spatial and temporal dimensions. With this approach, this study can provide important scientific basis and technical support for the health risk assessment and management of landfills.

Towards Fair Patient-Trial Matching via Patient-Criterion Level Fairness Constraint.

Clinical trials are indispensable in developing new treatments, but they face obstacles in patient recruitment and retention, hindering the enrollment of necessary participants. To tackle these challenges, deep learning frameworks have been created to match patients to trials. These frameworks calculate the similarity between patients and clinical trial eligibility criteria, considering the discrepancy between inclusion and exclusion criteria. Recent studies have shown that these frameworks outperform earlier approaches. However, deep learning models may raise fairness issues in patient-trial matching when certain sensitive groups of individuals are underrepresented in clinical trials, leading to incomplete or inaccurate data and potential harm. To tackle the issue of fairness, this work proposes a fair patient-trial matching framework by generating a patient-criterion level fairness constraint. The proposed framework considers the inconsistency between the embedding of inclusion and exclusion criteria among patients of different sensitive groups. The experimental results on real-world patient-trial and patient-criterion matching tasks demonstrate that the proposed framework can successfully alleviate the predictions that tend to be biased.