Gene-modified NK cells expressing CD64 and preloaded with HIV-specific BNAbs target autologous HIV-1-infected CD4+ T cells by ADCC.

Natural killer (NK) cells can efficiently mediate antibody-dependent cellular cytotoxicity (ADCC) of antibody coated target cells via the low-affinity Fc-receptor, CD16, but cannot retain antibodies over time. To increase antibody retention and facilitate targeted ADCC, we genetically modified human NK cells with the high-affinity Fc receptor, CD64, so that we could preload them with HIV-specific broadly neutralizing antibodies (BNAbs) and enhance their capacity to target HIV-infected cells via ADCC. Purified NK cells from the peripheral blood of control donors or persons living with HIV were activated with interleukin (IL)-2/IL-15/IL-21 cytokines and transduced with a lentivirus encoding CD64.

Prognosis of pulmonary hypertension in patients with hypertrophic cardiomyopathy: A multicenter propensity score matching study.

Objectives: Pulmonary hypertension (PH) is known to be associated with increased mortality in patients suffering from left ventricular disease. The aim of this study was to assess the incidence of PH among patients diagnosed with hypertrophic cardiomyopath (HCM) and to evaluate its prognostic significance.

Methods: The study cohort consisted of 2781 patients with HCM.

Effect of Ticagrelor Versus Clopidogrel After Off-Pump Coronary Artery Bypass Grafting on Postoperative Atrial Fibrillation: A Cohort Study.

Background: This study aimed to explore the effect of a P2Y inhibitor regimen on the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft surgery in carriers with the cytochrome P450 family 2 subfamily C member19 loss-of-function allele.

Methods And Results: From May 2019 to November 2023, patients containing the cytochrome P450 family 2 subfamily C member19*2 or *3 allele undergoing elective first-time off-pump coronary artery bypass graft surgery including aspirin 100 mg/d and ticagrelor 180 mg/d (AT group; n=95) versus clopidogrel 75 mg/d (aspirin and clopidogrel group; n=95) were prospectively followed. The primary end point was the cumulative incidence of POAF in a week.

Association of CYP2C19 genotypes with postoperative atrial fibrillation after coronary artery bypass surgery.

This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first-time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping.

Simultaneous Measurement of Group Refractive Index Dispersion and Thickness of Fused Silica Using a Scanning White Light Interferometer.

In this study, we simultaneously measured the group refractive index dispersion and thickness of fused silica using a scanning white light interferometer on a spectral range from 800 to 1050 nm. A delay error correction was performed using a He-Ne laser. The accuracy of the measured group refractive index dispersion of fused silica, when compared to the temperature-dependent Sellmeier equation, is within 4 × 10.

Sequential Exposure to IL21 and IL15 During Human Natural Killer Cell Expansion Optimizes Yield and Function.

Natural killer (NK) cells are frequently expanded for the clinic using irradiated, engineered K562 feeder cells expressing a core transgene set of membrane-bound (mb) IL15 and/or mbIL21 together with 41BBL. Prior comparisons of mbIL15 to mbIL21 for NK expansion lack comparisons of key attributes of the resulting NK cells, including their high-dimensional phenotype, polyfunctionality, the breadth and potency of cytotoxicity, cellular metabolism, and activity in xenograft tumor models. Moreover, despite multiple rounds of K562 stimulation, studies of sequential use of mbIL15- and mbIL21-based feeder cells are absent.

Analysis of genetic diversity and structure of Mongolian horse using microsatellite markers.

Mongolian horses are one of the oldest horse breeds, and are very important livestock in Mongolia as they are used in various fields such as transportation, food (milk, meat), and horse racing. In addition, research and preservation on pure Mongolian breeds are being promoted under the implementation of the new Genetics of Livestock Resources' act in Mongolia. However, despite the implementation of this act, genetic research on Mongolian horses using microsatellites (MS) has not progressed enough.

Thermal suppression of high-repetition rate SBS pulse compression in liquid media.

Thermal problems of high-repetition-rate stimulated Brillouin scattering (SBS) pulse compression in liquid media are theoretically and experimentally analyzed in detail. A wedge lens with less coma-aberration was designed using the ray tracing method and the thermally induced beam-pattern distortion was compensated by inhibiting thermal convection. The heat transfer form and fluid state were quantitatively analyzed for different SBS liquid media.

Clinical characteristics and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction: results from the China Cardiovascular Association Database-Heart Failure Center Registry.

Aim: We aimed to evaluate clinical characteristics and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction (HFpEF) from China. Factors associated with outcomes (hospitalization for HF [HHF] and cardiovascular [CV] death) were assessed.

Method And Results: Data were from the China Cardiovascular Association (CCA) Database-HF Center Registry.

Quantitative immunopeptidomics reveals a tumor stroma-specific target for T cell therapy.

T cell receptor (TCR)-based immunotherapy has emerged as a promising therapeutic approach for the treatment of patients with solid cancers. Identifying peptide-human leukocyte antigen (pHLA) complexes highly presented on tumors and rarely expressed on healthy tissue in combination with high-affinity TCRs that when introduced into T cells can redirect T cells to eliminate tumor but not healthy tissue is a key requirement for safe and efficacious TCR-based therapies. To discover promising shared tumor antigens that could be targeted via TCR-based adoptive T cell therapy, we employed population-scale immunopeptidomics using quantitative mass spectrometry across ~1500 tumor and normal tissue samples.

ARNI or ARB Treats Residual Left Ventricular Remodelling after Surgery for Valvular Regurgitation: ReReRe study protocol.

Aims: Patients with persistent or de novo left ventricular (LV) dilation and/or reduced ejection fraction (EF) after correction for primary aortic (AR) or mitral (MR) regurgitation (i.e. residual LV remodelling) have not been well studied with regard to guideline-directed medical therapy after successful aetiology-reversing surgery.

Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis.

Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous "inflammation brake.

Genetic diversity and population structure of Mongolian regional horses with 14 microsatellite markers.

Objective: This study aimed to identify the genetic diversity and population structure of Mongolian horse populations according to the province of residence (Khentii, KTP; Uvs, USP; Omnogovi and Dundgovi, GOP; Khovsgol, KGP) using 14 microsatellite (MS) markers.

Methods: A total of 269 whole blood samples were obtained from the four populations (KTP, USP, GOP, KGP) geographically distinct provinces. Multiplex polymerase chain reaction (PCR) was conducted using 14 MS markers (AHT4, ASB2, ASB17, ASB23, CA425, HMS1, HMS2, HMS3, HMS6, HMS7, HTG4, HTG6, HTG7, and VHL20), as recommended by the International Society for Animal Genetics.

NPM-ALK-Induced Reprogramming of Mature TCR-Stimulated T Cells Results in Dedifferentiation and Malignant Transformation.

Fusion genes including NPM-ALK can promote T-cell transformation, but the signals required to drive a healthy T cell to become malignant remain undefined. In this study, we introduce NPM-ALK into primary human T cells and demonstrate induction of the epithelial-to-mesenchymal transition (EMT) program, attenuation of most T-cell effector programs, reemergence of an immature epigenomic profile, and dynamic regulation of c-Myc, E2F, and PI3K/mTOR signaling pathways early during transformation. A mutant of NPM-ALK failed to bind several signaling complexes including GRB2/SOS, SHC1, SHC4, and UBASH3B and was unable to transform T cells.

CCR5-edited CD4+ T cells augment HIV-specific immunity to enable post-rebound control of HIV replication.

BackgroundWe conducted a phase I clinical trial that infused CCR5 gene-edited CD4+ T cells to determine how these T cells can better enable HIV cure strategies.MethodsThe aim of trial was to develop RNA-based approaches to deliver zinc finger nuclease (ZFN), evaluate the effect of CCR5 gene-edited CD4+ T cells on the HIV-specific T cell response, test the ability of infused CCR5 gene-edited T cells to delay viral rebound during analytical treatment interruption, and determine whether individuals heterozygous for CCR5 Δ32 preferentially benefit. We enrolled 14 individuals living with HIV whose viral load was well controlled by antiretroviral therapy (ART).

Impact of COVID-19 pandemic on patients with rare disease in Hong Kong.

The COVID-19 pandemic has had significant health, social, and economic consequences internationally. While the pandemic has direct implications on infected patients and families, there is a need to examine the pandemic's effect on patients with non-COVID-19-related diseases. This study examines the impact of the COVID-19 pandemic on 272 rare disease patients with 89 distinct rare diseases in Hong Kong using a cross-sectional online survey between April 10 and April 29, 2020 from the patient and caregiver perspective.

Sub-nanosecond stimulated Brillouin scattering pulse compression using HT270 for kHz repetition rate operation.

With mitigation of thermal effects in a generator cell based on a rotating off-centered lens, the effects of thermal blooming, self-defocusing, and thermal convection in the amplifier cell have experimentally proven to be the main factors limiting high-repetition-rate stimulated Brillouin scattering (SBS) pulse compression. To alleviate these effects, Galden HT270, which has a large viscosity coefficient, is used and compared experimentally. The operating repetition rate using HT270 was improved from 200 Hz to 1,000 Hz, comparable to the values in the literature.

Rotating off-centered lens in SBS phase conjugation mirror for high-repetition-rate operation.

A new method using a rotating off-centered lens is proposed to reduce the heat accumulation at the focal spot of a stimulated Brillouin scattering phase conjugation mirror at high-repetition-rate operation. Theoretical simulation of the beam intensity pattern at the focal point indicates there is less coma-aberration using a rotating off-centered focusing lens than with a rotating wedge and a conventional lens. The resultant SBS output parameters using this new method are substantially improved comparable to those of a non-rotating conventional method for high-repetition-rate operation, while the former operates quite well for higher power and the latter operates only for lower input power.

Remote ischaemic preconditioning ameliorates sinus rhythm restoration rate through Cox maze radiofrequency procedure associated with inflammation reaction reduction.

Remote ischaemic preconditioning (RIPC) as adjuvant to selective heart surgery attenuates cardiac injury and atrial fibrillation (AF) occurrence. We investigated its effect on sinus rhythm (SR) restoration rate in permanent AF patients undergoing Cox maze (CM) radiofrequency ablation with concomitant mitral valve surgery. From May 2013 to May 2017, 206 patients with rheumatic valve disease concomitant with permanent AF were randomized to receive prosthesis valve replacement and CM radiofrequency ablation procedure with (n = 104) or without (n = 102) RIPC (intermittent arm ischaemia through three cycles of 5-min inflation, followed by 5-min deflation of a blood pressure cuff).

Morphine induces dysfunction of PINK1/Parkin-mediated mitophagy in spinal cord neurons implying involvement in antinociceptive tolerance.

The development of opioid-induced analgesic tolerance is a clinical challenge in long-term use for managing chronic pain. The mechanisms of morphine tolerance are poorly understood. Mitochondria-derived reactive oxygen species (ROS) is a crucial signal inducing analgesic tolerance and pain.

Minimizing cross sectional pulse width difference between central and edge parts of SBS compressed beam.

For minimizing the spatial cross-sectional pulse width difference in the reflected SBS compressed beam, two new methods, blocking beam edge and parameter optimization, are proposed and compared experimentally. Results show that the sub-nanosecond compressed pulse width at the beam edge can be obtained by using both two methods in this paper. The pulse width difference between the beam center and the edge is minimized through selecting a proper medium and the optimized structural parameters in a single-cell SBS compressor.

Improved Expansion and Function of Patient T Cells by a Serum-free Medium.

Improvements to T cell culture systems that promote long-term engraftment and function of adoptively transferred T cells will likely result in superior clinical benefit to more individuals. To this end, we recently developed a chemically defined cell culture medium that robustly expands all T cell subsets in the absence of human serum. Using a humanized mouse model, we observed that T cells expanded in the absence of human serum provided durable control of tumors, whereas T cells expanded in medium supplemented with human serum only mediated transient control of tumor growth.