Structure and function of pancreatic lipase-related protein 2 and its relationship with pathological states

Pancreatic lipase is critical for the digestion and absorption of dietary fats. The most abundant lipolytic enzymes secreted by the pancreas are pancreatic triglyceride lipase (PTL or PNLIP) and its family members, pancreatic lipase-related protein 1 (PNLIPRP1or PLRP1) and pancreatic lipase-related protein 2 (PNLIPRP2 or PLRP2). Unlike the family\u27s other members, PNLIPRP2 plays an elemental role in lipid digestion, especially for newborns. Therefore, if genetic factors cause gene mutation, or other factors lead to non-expression, it may have an effect on fat digestion and absorption, on the susceptibility to pancreas and intestinal pathogens. In this review, we will summarize what is known about the structure and function of PNLIPRP2 and the levels of PNLIPRP2 and associated various pathological states

Heightening of an Existing Embankment Dam: Results from Numerical Simulations

The old dam of the Zhushou Reservoir is a clay core rock-debris dam with a maximum height of 63.4 m. After heightening, the new dam is a concrete-faced rockfill dam with a maximum height of 98.1 m. In the initial design stage, a rigid connection is proposed between the cutoff wall and toe slab. After the concrete cutoff wall is built at the axis of the old dam, a complete cutoff system is composed of cutoff wall, toe slab, and face slab. In this paper, based on the static and dynamic tests of dam materials, the Shen Zhujiang double-yield surface elastic-plastic model is used as the static constitutive model, and the contact friction model is used as the contact surface model. The three-dimensional finite element method is used to simulate the construction filling and water storage process during operation. The simulation results show that the maximum horizontal displacement occurs in the dam body of the old dam and the maximum settlement occurs at the interface between the old and new dams. During the storage period, the cutoff wall will not be damaged, and the tensile stress of the local area at the junction of toe slab and bank slope has exceeded the allowable value for C30 plain concrete, so the reinforcement should be strengthened at this location

Magnetic Borophenes from an Evolutionary Search

A computational methodology based on ab initio evolutionary algorithms and spin-polarized density functional theory was developed to predict two-dimensional magnetic materials. Its application to a model system borophene reveals an unexpected rich magnetism and polymorphism. A metastable borophene with nonzero thickness is an antiferromagnetic semiconductor from first-principles calculations, and can be further tuned into a half-metal by finite electron doping. In this borophene, the buckling and coupling among three atomic layers are not only responsible for magnetism, but also result in an out-of-plane negative Poisson\u27s ratio under uniaxial tension, making it the first elemental material possessing auxetic and magnetic properties simultaneously

Hsp47 Promotes Cancer Metastasis by Enhancing Collagen-Dependent Cancer Cell-Platelet Interaction

Increased expression of extracellular matrix (ECM) proteins in circulating tumor cells (CTCs) suggests potential function of cancer cell-produced ECM in initiation of cancer cell colonization. Here, we showed that collagen and heat shock protein 47 (Hsp47), a chaperone facilitating collagen secretion and deposition, were highly expressed during the epithelial-mesenchymal transition (EMT) and in CTCs. Hsp47 expression induced mesenchymal phenotypes in mammary epithelial cells (MECs), enhanced platelet recruitment, and promoted lung retention and colonization of cancer cells. Platelet depletion in vivo abolished Hsp47-induced cancer cell retention in the lung, suggesting that Hsp47 promotes cancer cell colonization by enhancing cancer cell–platelet interaction. Using rescue experiments and functional blocking antibodies, we identified type I collagen as the key mediator of Hsp47-induced cancer cell–platelet interaction. We also found that Hsp47-dependent collagen deposition and platelet recruitment facilitated cancer cell clustering and extravasation in vitro. By analyzing DNA/RNA sequencing data generated from human breast cancer tissues, we showed that gene amplification and increased expression of Hsp47 were associated with cancer metastasis. These results suggest that targeting the Hsp47/collagen axis is a promising strategy to block cancer cell–platelet interaction and cancer colonization in secondary organs

Enhanced Immune Responses Conferring Cross-Protection by Skin Vaccination With a Tri-Component Influenza Vaccine Using a Microneedle Patch

Skin vaccination using biodegradable microneedle patch (MNP) technology in vaccine delivery is a promising strategy showing significant advantages over conventional flu shots. In this study, we developed an MNP encapsulating a 4M2e-tFliC fusion protein and two types of whole inactivated influenza virus vaccines (H1N1 and H3N2) as a universal vaccine candidate. We demonstrated that mice receiving this tri-component influenza vaccine via MNP acquired improved IgG1 antibody responses with more balanced IgG1/IgG2a antibody responses and enhanced cellular immune responses, including increased populations of IL-4 and IFN-γ producing cells and higher frequencies of antigen-specific plasma cells compared with intramuscular injection. In addition, stronger germinal center reactions, increased numbers of Langerin-positive migratory dendritic cells, and increased cytokine secretion were observed in the skin-draining lymph nodes after immunization with the tri-component influenza MNP vaccine. The MNP-immunized group also possessed enhanced protection against a heterologous reassortant A/Shanghai/2013 H7N9 (rSH) influenza virus infection. Furthermore, the sera collected from 4M2e-tFliC MNP-immunized mice were demonstrated to have antiviral efficacy against reassortant A/Vietnam/1203/2004 H5N1 (rVet) and A/Shanghai/2013 H7N9 (rSH) virus challenges. The immunological advantages of skin vaccination with this tri-component MNP vaccine could offer a promising approach to develop an easily applicable and broadly protective universal influenza vaccine

Case report: Cervical brachytherapy technique for locally advanced cervical cancer in a patient with complete bicorporeal uterus

PurposeThe purpose of this study was to describe an approach to cervical brachytherapy for a patient with a complete bicorporeal uterus and locally advanced cervical cancer (LACC).Materials and methodsThe patient was a 53-year-old woman with a complete bicorporeal uterus, diagnosed with stage IIB cervical squamous cell carcinoma due to contact bleeding. The patient underwent concurrent chemoradiotherapy (CCRT), external beam pelvic radiotherapy with 45 Gy/25 fractions, and weekly cisplatin (40 mg/m2). Brachytherapy was administered following the completion of external beam radiotherapy.ResultsThe brachytherapy, which was CT (Computed Tomography)-guided using two CT-compatible tandems and two CT-compatible ovoids, delivered a prescription dose of HRCTV D90 was 6 Gy*5F, which achieved satisfactory dose coverage. The patient’s final HRCTV D90 EQD210 was 84.9 Gy, and IRCTV D90 EQD210 was 63.5 Gy. Rectum D2cc EQD23 was 66.03 Gy, bladder D2cc EQD23 was 75.57 Gy, sigmoid D2cc EQD23 was 63.93 Gy, and intestine D2cc EQD23 was 65.86 Gy. Follow-up at 1 year was CR.ConclusionsFor patients with cervical cancer and a complete bicorporeal uterus, using double tandems combined with double ovoids is a feasible treatment method to ensure adequate dose coverage without causing additional damage. This method is also applicable to patients with endometrial cancer

Platelet Secretion and Hemostasis Require Syntaxin-binding Protein STXBP5

Genome-wide association studies (GWAS) have linked genes encoding several soluble NSF attachment protein receptor (SNARE) regulators to cardiovascular disease risk factors. Because these regulatory proteins may directly affect platelet secretion, we used SNARE-containing complexes to affinity purify potential regulators from human platelet extracts. Syntaxin-binding protein 5 (STXBP5; also known as tomosyn-1) was identified by mass spectrometry, and its expression in isolated platelets was confirmed by RT-PCR analysis. Coimmunoprecipitation studies showed that STXBP5 interacts with core secretion machinery complexes, such as syntaxin-11/SNAP23 heterodimers, and fractionation studies suggested that STXBP5 also interacts with the platelet cytoskeleton. Platelets from Stxbp5 KO mice had normal expression of other key secretory components; however, stimulation-dependent secretion from each of the 3 granule types was markedly defective. Secretion defects in STXBP5-deficient platelets were confirmed via lumi-aggregometry and FACS analysis for P-selectin and LAMP-1 exposure. Interestingly, STXBP5-deficient platelets had altered granule cargo levels, despite having normal morphology and granule numbers. Consistent with secretion and cargo deficiencies, Stxbp5 KO mice showed dramatic bleeding in the tail transection model and defective hemostasis in the FeCl3-induced carotid injury model. Transplantation experiments indicated that these defects were due to loss of STXBP5 in BM-derived cells. Our data demonstrate that STXBP5 is required for normal arterial hemostasis, due to its contributions to platelet granule cargo packaging and secretion

Analysis on time delay of tuberculosis among adolescents and young adults in Eastern China

BackgroundTuberculosis (TB) is recognized as a significant global public health concern. Still, there remains a dearth of comprehensive evaluation regarding the specific indicators and their influencing factors of delay for adolescents and young adults.MethodsAll notified pulmonary TB (PTB) patients in Jiaxing City were collected between 2005 and 2022 from China’s TB Information Management System. Logistic regression models were conducted to ascertain the factors that influenced patient and health system delays for PTB cases, respectively. Furthermore, the impact of the COVID-19 pandemic on local delays has been explored.ResultsFrom January 1, 2005 to December 31, 2022, a total of 5,282 PTB cases were notified in Jiaxing City, including 1,678 adolescents and 3,604 young adults. For patient delay, female (AOR: 1.18, 95%CI: 1.05–1.32), PTB complicated with extra-pulmonary TB (AOR: 1.70, 95% CI: 1.28–2.26), passive case finding (AOR: 1.46, 95% CI: 1.07–1.98) and retreatment (AOR: 1.52, 95% CI: 1.11–2.09) showed a higher risk of delay. For health system delay, minorities (AOR: 0.69, 95% CI: 0.53–0.90) and non-students (AOR: 0.83, 95% CI: 0.71–0.98) experienced a lower delay. Referral (AOR: 1.46, 95% CI: 1.29–1.65) had a higher health system delay compared with clinical consultation. Furthermore, county hospitals (AOR: 1.47, 95% CI: 1.32–1.65) and etiological positive results (AOR: 1.46, 95% CI: 1.30–1.63) were associated with comparatively high odds of patient delay. Contrarily, county hospitals (AOR: 0.88, 95% CI: 0.78–1.00) and etiological positive results (AOR: 0.67, 95% CI: 0.59–0.74) experienced a lower health system delay. Besides, the median of patient delay, health system delay, and total delay during the COVID-19 pandemic were significantly lower than that before.ConclusionIn general, there has been a noteworthy decline in the notification rate of PTB among adolescents and young adults in Jiaxing City while the declining trend was not obvious in patient delay, health system delay, and total delay, respectively. It also found factors such as gender, case-finding method, and the hospital level might influence the times of seeking health care and diagnosis in health agencies. These findings will provide valuable insights for refining preventive and treatment strategies for TB among adolescents and young adults