Pullulan Polysaccharide as an Eco-Friendly Depressant for Flotation Separation of Chalcopyrite and Molybdenite.

It is difficult to separate molybdenite and chalcopyrite by froth flotation due to the good floatability of the two minerals. In this paper, the separation of copper-molybdenum sulfide minerals was realized by using pullulan polysaccharide (PU) as the depressant. The flotation test results showed that the copper concentrate grade increased from 16.24 to 29.86%, and the copper concentrate recovery reached 83.55% under low alkali conditions. The selective separation mechanism of the two minerals by PU was revealed through contact angle measurements, ζ-potential measurements, Fourier transform infrared (FTIR) spectroscopy analyses, and X-ray photoelectron spectroscopy (XPS) analyses. The ζ-potential and contact angle results showed that PU is more easily adsorbed on molybdenite to strengthen the hydrophilicity of molybdenite. The FTIR and XPS results showed that PU is adsorbed on molybdenite by physical interactions, and hydrophobic interactions and hydrogen bonding play a major role.

Fast, high-quality, and unshielded 0.2 T low-field mobile MRI using minimal hardware resources.

OBJECTIVE: To propose a deep learning-based low-field mobile MRI strategy for fast, high-quality, unshielded imaging using minimal hardware resources. METHODS: Firstly, we analyze the correlation of EMI signals between the sensing coil and the MRI coil to preliminarily verify the feasibility of active EMI shielding using a single sensing coil. Then, a powerful deep learning EMI elimination model is proposed, which can accurately predict the EMI components in the MRI coil signals using EMI signals from at least one sensing coil. Further, deep learning models with different task objectives (super-resolution and denoising) are strategically stacked for multi-level post-processing to enable fast and high-quality low-field MRI. Finally, extensive phantom and brain experiments were conducted on a home-built 0.2 T mobile brain scanner for the evaluation of the proposed strategy. RESULTS: 20 healthy volunteers were recruited to participate in the experiment. The results show that the proposed strategy enables the 0.2 T scanner to generate images with sufficient anatomical information and diagnostic value under unshielded conditions using a single sensing coil. In particular, the EMI elimination outperforms the state-of-the-art deep learning methods and numerical computation methods. In addition, 2 × super-resolution (DDSRNet) and denoising (SwinIR) techniques enable further improvements in imaging speed and quality. DISCUSSION: The proposed strategy enables low-field mobile MRI scanners to achieve fast, high-quality imaging under unshielded conditions using minimal hardware resources, which has great significance for the widespread deployment of low-field mobile MRI scanners.

Biomimetic nanomedicine cocktail enhances selective targeting for ovarian Cancer chemo- and immunotherapy.

Ovarian cancer is one of the deadliest cancers, and combined chemo- and immunotherapies are potential strategies to combat it. However, the anti-cancer efficacy of the combined therapies may be limited by the non-selective co-delivery of chemotherapy and immunotherapy. Herein, a combined chemo- and immunotherapy is designed to selectively target ovarian tumor (ID8) cells and dendritic cells (DCs) using ID8 cell membrane (IM) and bacterial outer membrane vesicles (OMVs), respectively. Doxorubicin (DOX) and Ovalbumin (OVA) peptide (OVA257-264) are chosen as model chemotherapy and immunotherapy agents, respectively. A DNA nanocube capable of easily loading DOX or OVA257-264 is chosen as the carrier. Firstly, the DNA nanocube is used to load DOX or OVA257-264 to prepare cube-DOX or cube-OVA. This nanocube was then encapsulated with IM to form IM@Cube-DOX and with OMV to form OMV@Cube-OVA. IM@Cube-DOX can be selectively taken up by ID8 cells, leading to effective cell killing, while OMV@Cube-OVA targets and activates DC2.4 cells in vitro. Both IM@Cube-DOX and OMV@Cube-OVA show increased accumulation at ID8 tumors in C57BL/6 mice. Combined IM@Cube-DOX + OMV@Cube-OVA therapy demonstrates better anti-tumor efficacy than non-selective delivery methods such as OMV@(Cube-DOX + Cube-OVA) or IM@(Cube-DOX + Cube-OVA) in ID8-OVA tumor-bearing mice. In conclusion, this study demonstrates a biomimetic delivery strategy that enables selective drug delivery to tumor cells and DCs, thereby enhancing the anti-tumor efficacy of combined chemo- and immunotherapy through the selective delivery strategy.

Dual Nickel/Photoredox-Catalyzed Arylsulfonylation of Allenes.

The nickel/photoredox dual catalysis system is an efficient conversion platform for the difunctionalization of unsaturated hydrocarbons. Herein, we disclose the first dual nickel/photoredox-catalyzed intramolecular 1,2-arylsulfonylation of allenes, which can accurately construct a C(sp2)-C(sp2) bond and a C(sp3)-S bond. The reaction exhibits excellent chemoselectivity and regioselectivity, allowing modular conformations of a diverse series of 3-sulfonylmethylbenzofuran derivatives. Control experiments showed that the bipyridine ligand is crucial for the formation of a stable σ-alkyl nickel intermediate, providing the possibility for sulfonyl radical insertion. Meanwhile, the electrophilic sulfonyl radical facilitates further oxidative addition of the σ-alkyl nickel intermediate and inhibits addition with allenes. In addition, control experiments, cyclic voltammetry tests, Stern-Volmer experiments, and density functional theory calculations afford evidence for the Ni(0)/Ni(I)/Ni(II)/Ni(III) pathway in this 1,2-arylsulfonylation.

Silver-catalyzed P-centered anion nucleophilic addition to isocyanide: access to 2-phosphinoyl indoles/indol-3-ols.

A silver-catalyzed chemoselective cascade nucleophilic addition of a P-centered anion to isocyanides and cyclization reaction was developed for the efficient and practical synthesis of a wide range of 2-phosphinoyl indole and indol-3-ol derivatives. Unlike the well-documented synthesis of phosphorus-functionalized heterocycles via a P-centered radical, an anionic reactivity profile of phosphine oxides is most likely involved in this domino transformation.

Mice fatal pneumonia model induced by less-virulent Streptococcus pneumoniae via intratracheal aerosolization.

Aim: Animal models of fatal pneumonia caused by Streptococcus pneumoniae (Spn) have not been reliably generated using many strains of less virulent serotypes. Materials & methods: Pulmonary infection of a less virulent Spn serotype1 strain in the immunocompetent mice was established via the intratracheal aerosolization (ITA) route. The survival, local and systemic bacterial spread, pathological changes and inflammatory responses of this model were compared with those of mice challenged via the intratracheal instillation, intranasal instillation and intraperitoneal injection routes. Results: ITA and intratracheal instillation both induced fatal pneumonia; however, ITA resulted in better lung bacterial deposition and distribution, pathological homogeneity and delivery efficiency. Conclusion: ITA is an optimal route for developing animal models of severe pulmonary infections.

What is this article about? Streptococcus pneumoniae (Spn), a type of bacteria, can cause serious illness and death in otherwise healthy people. One way that we study pneumonia is using animals. However, pneumonia in animals infected with Spn in the laboratory does not mimic that in humans very well. To study this illness, we need a new way to set up a proper animal model.What were the results? This study set up a method called intratracheal aerosolization (ITA). In ITA, bacteria can form small droplets called aerosols and reach the deepest parts of a mouse's lung. ITA can cause deadly illness in mice infected with Spn, even if the mice are healthy.What do the results of the study mean? The ITA method could be a useful tool to set up animal models of serious pneumonia with less virulent bacteria.

PtbNet: Based on Local Few-Shot Classes and Small Objects to accurately detect PTB.

Pulmonary Tuberculosis (PTB) is one of the world's most infectious illnesses, and its early detection is critical for preventing PTB. Digital Radiography (DR) has been the most common and effective technique to examine PTB. However, due to the variety and weak specificity of phenotypes on DR chest X-ray (DCR), it is difficult to make reliable diagnoses for radiologists. Although artificial intelligence technology has made considerable gains in assisting the diagnosis of PTB, it lacks methods to identify the lesions of PTB with few-shot classes and small objects. To solve these problems, geometric data augmentation was used to increase the size of the DCRs. For this purpose, a diffusion probability model was implemented for six few-shot classes. Importantly, we propose a new multi-lesion detector PtbNet based on RetinaNet, which was constructed to detect small objects of PTB lesions. The results showed that by two data augmentations, the number of DCRs increased by 80% from 570 to 2,859. In the pre-evaluation experiments with the baseline, RetinaNet, the AP improved by 9.9 for six few-shot classes. Our extensive empirical evaluation showed that the AP of PtbNet achieved 28.2, outperforming the other 9 state-of-the-art methods. In the ablation study, combined with BiFPN+ and PSPD-Conv, the AP increased by 2.1, APs increased by 5.0, and grew by an average of 9.8 in APm and APl. In summary, PtbNet not only improves the detection of small-object lesions but also enhances the ability to detect different types of PTB uniformly, which helps physicians diagnose PTB lesions accurately. The code is available at https://github.com/Wenhui-person/PtbNet/tree/master.

Securinine inhibits carcinogenesis in gastric cancer by targeting AURKA-ß-catenin/Akt/STAT3 and the cell cycle pathway.

BACKGROUND: Gastric cancer (GC) is difficult to treat with currently available treatments. Securinine (SCR) has a lengthy history of use in the treatment of disorders of the nervous system, and its anticancer potential has been gaining attention in recent years. The aim of this study was to explore the repressive effect of SCR on GC and its fundamental mechanism. METHODS: The efficacy of SCR in GC cells was detected by MTT assays. Colony formation, flow cytometry and Transwell assays were used to assess the changes in the proliferation, apoptosis, cell cycle distribution, migration and invasion of GC cells after treatment. AGS (human gastric carcinoma cell)-derived xenografts were used to observe the effect of SCR on tumor growth in vivo. The molecular mechanism of action of SCR in GC was explored via RNA sequencing, bioinformatics analysis, Western blotting, molecular docking, and immunohistochemistry. RESULTS: SCR was first discovered to inhibit the proliferation, migration, and invasion of GC cells while initiating apoptosis and cell cycle arrest in vitro. It was also established that SCR has excellent anticancer effects in vivo. Interestingly, AURKA acts as a crucial target of SCR, and AURKA expression can be blocked by SCR. Moreover, this study revealed that SCR suppresses the cell cycle and the ß-catenin/Akt/STAT3 pathways, which were previously reported to be regulated by AURKA. CONCLUSION: SCR exerts a notable anticancer effect on GC by targeting AURKA and blocking the cell cycle and ß-catenin/Akt/STAT3 pathway. Thus, SCR is a promising pharmacological option for the treatment of GC.

Molecular Simulation Study on the Hydrogen Permeation Behavior and Mechanism of Common Polymers.

This research aimed to provide an understanding of the selection and safe application of pipeline liner materials for hydrogen transport by examining the permeation properties and mechanisms of hydrogen within polymers commonly used for this purpose, such as high-density polyethylene (HDPE) and ethylene-vinyl alcohol copolymer (EVOH), through molecular simulation. The study was carried out within defined operational parameters of temperature (ranging from room temperature to 80 °C) and pressure (from 2.5 to 10 MPa) that are pertinent to hydrogen pipeline infrastructures. The results reveal that with an increase in temperature from 30 °C to 80 °C, the solubility, diffusion, and permeability coefficients of hydrogen in HDPE increase by 18.7%, 92.9%, and 129.0%, respectively. Similarly, in EVOH, these coefficients experience increments of 15.9%, 81.6%, and 112.7%. Conversely, pressure variations have a negligible effect on permeability in both polymers. HDPE exhibits significantly higher hydrogen permeability compared to EVOH. The unique chain segment configuration of EVOH leads to the formation of robust hydrogen bonds among the hydroxyl groups, thereby impeding the permeation of hydrogen. The process by which hydrogen is adsorbed in polymers involves aggregation at low potential energy levels. During diffusion, the hydrogen molecule primarily vibrates within a limited range, with intermittent occurrences of significant hole-to-hole transitions over larger distances. Hydrogen exhibits a stronger interaction with HDPE compared to EVOH, leading to a higher number of adsorption sites and increased hydrogen adsorption capacity in HDPE. Hydrogen molecules move more actively in HDPE than in EVOH, exhibiting greater hole amplitude and more holes in transition during the diffusion process.

PD-1 antibody in combination with chemotherapy for the treatment of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum: Two case reports.

BACKGROUND: SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting (SWI/SNF) complexes and plays an essential role in oncogenesis. SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis. There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies. Programmed death 1 (PD-1) antibodies, known as immune checkpoint inhibitor antibodies, potentially play a role in treating gastrointestinal tract malignancies. CASE SUMMARY: We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum. For both patients, SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein, while TP53 gene mutations were observed via next-generation sequencing. Both patients were administered chemotherapy in combination with an anti-PD-1 antibody. The two patients exhibited completely different responses to treatment and had different prognoses. Case 1 experienced rapid progression after PD-1 infusion and chemotherapy, case 2 experienced a remarkable response after treatment, and the progression-free survival was more than 6 months. CONCLUSION: This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum. PD-1 combined with chemotherapy showed a certain efficacy in select patients, providing options for treating these highly malignant tumors. Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.

Arsenic field test kits based on solid-phase fluorescence filter effect induced by silver nanoparticle formation.

Millions of people worldwide are affected by naturally occurring arsenic in groundwater. The development of a low-cost, highly sensitive, portable assay for rapid field detection of arsenic in water is important to identify areas for safe wells and to help prioritize testing. Herein, a novel paper-based fluorescence assay was developed for the on-site analysis of arsenic, which was constructed by the solid-phase fluorescence filter effect (SPFFE) of AsH3-induced the generation of silver nanoparticles (AgNPs) toward carbon dots. The proposed SPFFE-based assay achieves a low arsenic detection limit of 0.36 µg/L due to the efficient reduction of Ag+ by AsH3 and the high molar extinction coefficient of AgNPs. In conjunction with a smartphone and an integrated sample processing and sensing platform, field-sensitive detection of arsenic could be achieved. The accuracy of the portable assay was validated by successfully analyzing surface and groundwater samples, with no significant difference from the results obtained through mass spectrometry. Compared to other methods for arsenic analysis, this developed system offers excellent sensitivity, portability, and low cost. It holds promising potential for on-site analysis of arsenic in groundwater to identify safe well locations and quickly obtain output from the global map of groundwater arsenic.

Electrochemical Azo-free Mitsunobu-type Reaction.

The classic chemical Mitsunobu reaction suffers from the need of excess alcohol activation reagents and the generation of significant by-products. Efforts to overcome these limitations have resulted in numerous creative solutions, but the substrate scope of these catalytic processes remains limited. Here we report an electrochemical Mitsunobu-type reaction, which features azo-free alcohol activation and broad substrate scope. This user-friendly technology allows a vast collection of heterocycles as the nucleophile, which can couple with a series of chiral cyclic and acyclic alcohols in moderate to high yields and excellent ee's. This practical reaction is scalable, chemoselective, uses simple Electrasyn setup with inexpensive electrodes and requires no precaution to exclude air and moisture. The synthetic utility is further demonstrated on the structural modification of diverse bioactive natural products and pharmaceutical derivatives and its straightforward application in a multiple-step synthesis of a drug candidate.

Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses.

The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.

Portable purge and trap-microplasma optical emission spectrometric device for field detection of iodine in water.

Iodine is essential for human growth and can enter the body through food, water, and air. Analyzing its presence in the environment is crucial for ensuring healthy human development. However, current large-scale instruments have limitations in the field analysis of iodine. Herein, a miniaturized purge and trap point discharge microplasma optical emission spectrometric (P&T-µPD-OES) device was developed for the field analysis of iodine in water. Volatile iodine molecules were produced from total inorganic iodine (TII) through a basic redox reaction under acidic conditions, then the purge and trap module effectively separated and preconcentrated iodine molecules. The iodine molecules were subsequently atomized and excited by the integrated point discharge microplasma and an iodine atomic emission line at 206.24 nm was monitored by the spectrometer. Under optimal conditions, this proposed method had a detection limit of 16.2 µg L-1 for iodine and a precision better than 4.8%. Besides, the accuracy of the portable device was validated by successful analysis of surface and groundwater samples and a comparison of the mass spectrometry method. This proposed portable, low-power device is expected to support rapid access to iodine levels and distribution in water.

Multi-target field control for matrix gradient coils.

OBJECTIVE: Conventional single-target field control for matrix gradient coils will add control complexity in MRI spatial encoding, such as designing specialized fields and sequences. This complexity can be reduced by multi-target field control, which is realized by optimizing the coil structure according to target fields. METHODS: Based on the principle of multi-target field control, the X, Y and Z gradient fields can be set as target fields, and all coil elements can then be divided into three groups to generate these fields. An improved simulated annealing algorithm is proposed to optimize the coil element distribution of each group to generate the corresponding target field. In the improved simulated annealing process, two swapping modes are presented, and randomly selected with certain probabilities that are set to 0.25, 0.5 and 0.75, respectively. The flexibility of the final designed structure is demonstrated by a spherical harmonic basis up to the full second order with single-target field control. An experimental platform is built to measure the gradient fields generated by the designed structure with multi-target target control. RESULTS: With three probabilities of swapping modes, three similar coil element distributions are optimized, and their maximum magnetic field errors for generating X, Y and Z gradients are all below 5%. The structure selected for the final design is the one with a probability of 0.75, considering the coil performance and structural symmetry. The maximum error for all target fields generated by single-target field control is also below 5%. The experimental results show that the measured gradient fields along the axes have enough strength and high linearity. CONCLUSIONS: With the proposed improved simulated annealing algorithm and swapping modes, multi-target field control for matrix gradient coils is verified and achieved in this study by optimizing the coil element distribution. Moreover, this study provides a solution to simplify the complexity of controlling the matrix gradient coil in spatial encoding.

Long-read sequencing reveals the structural complexity of genomic integration of HPV DNA in cervical cancer cell lines.

BACKGROUND: Cervical cancer (CC) causes more than 311,000 deaths annually worldwide. The integration of human papillomavirus (HPV) is a crucial genetic event that contributes to cervical carcinogenesis. Despite HPV DNA integration is known to disrupt the genomic architecture of both the host and viral genomes in CC, the complexity of this process remains largely unexplored. RESULTS: In this study, we conducted whole-genome sequencing (WGS) at 55-65X coverage utilizing the PacBio long-read sequencing platform in SiHa and HeLa cells, followed by comprehensive analyses of the sequence data to elucidate the complexity of HPV integration. Firstly, our results demonstrated that PacBio long-read sequencing effectively identifies HPV integration breakpoints with comparable accuracy to targeted-capture Next-generation sequencing (NGS) methods. Secondly, we constructed detailed models of complex integrated genome structures that included both the HPV genome and nearby regions of the human genome by utilizing PacBio long-read WGS. Thirdly, our sequencing results revealed the occurrence of a wide variety of genome-wide structural variations (SVs) in SiHa and HeLa cells. Additionally, our analysis further revealed a potential correlation between changes in gene expression levels and SVs on chromosome 13 in the genome of SiHa cells. CONCLUSIONS: Using PacBio long-read sequencing, we have successfully constructed complex models illustrating HPV integrated genome structures in SiHa and HeLa cells. This accomplishment serves as a compelling demonstration of the valuable capabilities of long-read sequencing in detecting and characterizing HPV genomic integration structures within human cells. Furthermore, these findings offer critical insights into the complex process of HPV16 and HPV18 integration and their potential contribution to the development of cervical cancer.

T-cell infiltration and its regulatory mechanisms in cancers: insights at single-cell resolution.

Tumor-infiltrating T cells recognize, attack, and clear tumor cells, playing a central role in antitumor immune response. However, certain immune cells can impair this response and help tumor immune escape. Therefore, exploring the factors that influence T-cell infiltration is crucial to understand tumor immunity and improve therapeutic effect of cancer immunotherapy. The use of single-cell RNA sequencing (scRNA-seq) allows the high-resolution analysis of the precise composition of immune cells with different phenotypes and other microenvironmental factors, including non-immune stromal cells and the related molecules in the tumor microenvironment of various cancer types. In this review, we summarized the research progress on T-cell infiltration and the crosstalk of other stromal cells and cytokines during T-cell infiltration using scRNA-seq to provide insights into the mechanisms regulating T-cell infiltration and contribute new perspectives on tumor immunotherapy.

A metal-organic framework (MOF) built on surface-modified Cu nanoparticles eliminates tumors via multiple cascading synergistic therapeutic effects.

Tumors produce a hypoxic environment that greatly influences cancer treatment, and conventional chemotherapeutic drugs cannot selectively accumulate in the tumor region because of the lack of a tumor targeting mechanism, causing increased systemic toxicities and side effects. Hence, designing and developing new nanoplatforms that combine multimodal therapeutic regimens is essential to improve tumor therapeutic efficacy. Herein, we report the synthesis of ultrafine Cu nanoparticles loaded with a drug combination of cisplatin (Pt) and 1-methyl-d-tryptophan (1-MT) and externally coated with 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) photosensitizer, polydopamine (PDA) and CaO2 of MIL-101(Fe) as a new nanoplatform (Cu@MIL-101@PMTPC). The nanoplatform synergistically combined chemodynamic therapy (CDT), photodynamic therapy (PDT), and immunochemotherapy. The Fe3+ in MIL-101(Fe) and the surface Cu nanoparticles exhibited strong ability to consume intracellular glutathione (GSH), thereby generating a Fenton-like response in the tumor microenvironment (TME) with substantial peroxidase (POD)-like and superoxide dismutase (SOD)-like activities. In this design, we used the indoleamine 2,3-dioxygenase (IDO) inhibitor 1-MT to overcome chemotherapy-induced immune escape phenomena including enhanced CD8+ and CD4+ T cell expression, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) production, and accelerated immunogenic cell death. The targeted release of cisplatin loaded into Cu@MIL-101@PMTPC also reduced toxic side effects of chemotherapy. TCPP generated a large amount of singlet oxygen (1O2) upon specific laser irradiation to effectively kill tumor cells. CaO2 on the outer layer generated oxygen (O2) and hydrogen peroxide (H2O2) to ameliorate hypoxia in the tumor microenvironment, enhance the PDT effect, and provide a continuous supply of H2O2 for the Fenton-like reaction. Thus, this nanocarrier platform exhibited a powerful chemodynamic, photodynamic, and immunochemotherapeutic cascade, providing a new strategy for cancer treatment.

Knockdown of SQLE promotes CD8+ T cell infiltration in the tumor microenvironment.

Cholesterol biosynthesis and metabolism are critical aspects that shape the process of tumor development and associated microenvironmental conditions owing to the ability of cholesterol to drive tumor growth and invasion. Squalene Epoxidase (SQLE) is the second rate-limiting enzyme involved in the synthesis of cholesterol. The functional role of SQLE within the tumor microenvironment, however, has yet to be established. Here we show that SQLE is distinctively expressed across most types of cancer, and the expression level is highly correlated with tumor mutation burden and microsatellite instability. Accordingly, SQLE was identified as a prognostic risk factor in cancer patients. In addition, we observed a negative correlation between SQLE expression and immune cell infiltration across multiple cancers, and murine xenograft model further confirmed that SQLE knockdown was associated with enhanced intratumoral CD8+ T cell infiltration. Using next-generation sequencing, we identified 410 genes distinctively expressed in tumors exhibiting SQLE inhibition. KEGG and GO analysis further verified that SQLE altered the immune response in the tumor microenvironment. Furthermore, we found that the metabolism and translation of proteins is the main binding factor with SQLE. Our findings ascertain that SQLE is a potential target in multiple cancers and suppressing SQLE establishes an essential mechanism for shaping tumor microenvironment.

Avoiding unnecessary biopsy: the combination of PRIMARY score with prostate-specific antigen density for prostate biopsy decision.

BACKGROUND: Avoiding unnecessary biopsies for men with suspected prostate cancer remains a clinical priority. The recently proposed PRIMARY score improves diagnostic accuracy in detecting clinically significant prostate cancer (csPCa). The aim of this study was to determine the best strategy combining PRIMARY score or MRI reporting scores (Prostate Imaging Reporting and Data System [PI-RADS]) with prostate-specific antigen density (PSAD) for prostate biopsy decision making. METHODS: A retrospective analysis of 343 patients who underwent both 68Ga-PSMA PET/CT and MRI before prostate biopsy was performed. PSA was restricted to <20 ng/ml. Different biopsy strategies were developed and compared based on PRIMARY score or PI-RADS with PSAD thresholds. Decision curve analysis (DCA) was plotted to define the optimal biopsy strategy. RESULTS: The prevalence of csPCa was 41.1% (141/343). According to DCA, the strategies of PRIMARY score +PSAD (strategy #1, strategy #2, strategy #6) had a higher net benefit than the strategies of PI-RADS + PSAD at the risk threshold of 8-20%. The best diagnostic strategy was strategy #1 (PRIMARY score 4-5 or PSAD ≥ 0.20), which avoided 38.2% biopsy procedures while missed 9.2% of csPCa cases. From a clinical perspective, strategies with a lower risk of missing csPCa were strategy #2 (PRIMARY score ≥4 or PSAD ≥ 0.15), which avoided 28.6% biopsies while missed 5.7% of csPCa cases, or strategy #6 (PRIMARY score≥3 or PSAD ≥ 0.15), which avoided 20.7% biopsies while missed only 3.5% of csPCa cases. The limitations of the study were the retrospective single-center nature. CONCLUSIONS: The combination of PRIMARY score +PSAD allows individualized decisions to avoid unnecessary biopsy, outperforming the strategies of PI-RADS + PSAD. Further prospective trials are needed to validate these findings.