The emerging role of sacubitril/valsartan in pulmonary hypertension with heart failure.

Pulmonary hypertension due to left heart disease (PH-LHD) represents approximately 65%-80% of all patients with PH. The progression, prognosis, and mortality of individuals with left heart failure (LHF) are significantly influenced by PH and right ventricular (RV) dysfunction. Consequently, cardiologists should devote ample attention to the interplay between HF and PH. Patients with PH and HF may not receive optimal benefits from the therapeutic effects of prostaglandins, endothelin receptor antagonists, or phosphodiesterase inhibitors, which are specific drugs for pulmonary arterial hypertension (PAH). Sacubitril/valsartan, the angiotensin receptor II blocker-neprilysin inhibitor (ARNI), was recommended as the first-line therapy for patients with heart failure with reduced ejection fraction (HFrEF) by the 2021 European Society of Cardiology Guidelines. Although ARNI is effective in treating left ventricular (LV) enlargement and lower ejection fraction, its efficacy in treating individuals with PH and HF remains underexplored. Considering its vasodilatory effect at the pre-capillary level and a natriuretic drainage role at the post-capillary level, ARNI is believed to have a broad range of potential applications in treating PH-LHD. This review discusses the fundamental pathophysiological connections between PH and HF, emphasizing the latest research and potential benefits of ARNI in PH with various types of LHF and RV dysfunction.

A root phloem pole cell atlas reveals common transcriptional states in protophloem-adjacent cells.

Single-cell sequencing has recently allowed the generation of exhaustive root cell atlases. However, some cell types are elusive and remain underrepresented. Here we use a second-generation single-cell approach, where we zoom in on the root transcriptome sorting with specific markers to profile the phloem poles at an unprecedented resolution. Our data highlight the similarities among the developmental trajectories and gene regulatory networks common to protophloem sieve element (PSE)-adjacent lineages in relation to PSE enucleation, a key event in phloem biology. As a signature for early PSE-adjacent lineages, we have identified a set of DNA-binding with one finger (DOF) transcription factors, the PINEAPPLEs (PAPL), that act downstream of PHLOEM EARLY DOF (PEAR) genes and are important to guarantee a proper root nutrition in the transition to autotrophy. Our data provide a holistic view of the phloem poles that act as a functional unit in root development.

Identification of Genomic Regions Associated with Vine Growth and Plant Height of Soybean.

Vining growth (VG) and high plant height (PH) are the physiological traits of wild soybean that preclude their utilization for domesticated soybean breeding and improvement. To identify VG- and PH-related quantitative trait loci (QTLs) in different genetic resources, two populations of recombinant inbred lines (RILs) were developed by crossing a cultivated soybean, Zhonghuang39 (ZH39), with two wild soybean accessions, NY27-38 and NY36-87. Each line from the two crosses was evaluated for VG and PH. Three QTLs for VG and three for PH, detected in the ZH39 × NY27-38 population of the RILs, co-located on chromosomes 2, 17 and 19. The VG- and PH-related QTL in the ZH39 × NY36-87 population co-located on chromosome 19. A common QTL shared by the two populations was located on chromosome 19, suggesting that this major QTL was consistently selected for in different genetic backgrounds. The results suggest that different loci are involved in the domestication or adaptations of soybean of various genetic backgrounds. The molecular markers presented here would benefit the fine mapping and cloning of candidate genes underlying the VG and PH co-localized regions and thus facilitate the utilization of wild resources in breeding by avoiding undesirable traits.

Extracellular Mitochondrial Components and Effects on Cardiovascular Disease.

Besides being powerhouses of the cell, mitochondria released into extracellular space act as intercellular signaling. Mitochondria and their components mediate cell-to-cell communication in free form or embedded in a carrier. The pathogenesis of cardiovascular disease is complex, which shows close relationship with inflammation and metabolic abnormalities. Since mitochondria sustain optimal function of the heart, extracellular mitochondria are emerging as a key regulator in the development of cardiovascular disease. In this review, we provide recent findings in the presence and forms of mitochondria transfer between cells, as well as the effects of these mitochondria on vascular inflammation and ischemic myocardium. Mitochondrial transplantation is a novel treatment paradigm for patients suffering from acute cardiovascular accident and challenges the traditional methods of mitochondria isolation.

Lifetime Risks, Life Expectancy, and Health Care Expenditures for Rheumatoid Arthritis: A Nationwide Cohort Followed Up From 2003 to 2016.

OBJECTIVE: This study was undertaken to estimate the cumulative incidence rate of rheumatoid arthritis (RA) in the Taiwanese population ages 16-84 years, and life expectancy, loss of life expectancy, and lifetime health care expenditures for incident RA in Taiwan after 2003, when biologics began to be prescribed. METHODS: We obtained all claims data for the period 1999 to 2016 from the National Health Insurance program of Taiwan, and validated the data against the Catastrophic Illness Registry to establish the study cohort. We estimated the survival function for RA and extrapolated to lifetime using a rolling-over algorithm. For every RA case, we simulated sex-, age-, and calendar year-matched referents from vital statistics and estimated their life expectancy. The difference between the life expectancy of the referent and the life expectancy of the RA patient was the loss of life expectancy for the RA patient. Average monthly health care expenditures were multiplied by the corresponding survival rates and summed up throughout the lifetime to calculate the lifetime health care expenditures. RESULTS: A total of 29,352 new RA cases were identified during 2003-2016. There was a decreasing trend in cumulative incidence rate in those ages 16-84 for both sexes. Mean life expectancy after diagnosis of RA was 26.3 years, and mean lifetime cost was $72,953. RA patients had a mean loss of life expectancy of 4.97 years. Women with RA survived 1-2 years longer than men with RA of the same age, which resulted in higher lifetime expenditures for the former. Since the life expectancy for women in Taiwan was 6-7 years higher than that for men, the loss of life expectancy for women with RA was higher than that for men with RA. Annual health care expenditures were similar for both sexes. CONCLUSION: Our findings indicate that since biologics became available, RA patients have lived longer and had higher lifetime expenditures, which should be monitored and evaluated for cost-effectiveness.

Ultrasonic Fingerprint Sensor With Transmit Beamforming Based on a PMUT Array Bonded to CMOS Circuitry.

In this paper, we present a single-chip 65 ×42 element ultrasonic pulse-echo fingerprint sensor with transmit (TX) beamforming based on piezoelectric micromachined ultrasonic transducers directly bonded to a CMOS readout application-specific integrated circuit (ASIC). The readout ASIC was realized in a standard 180-nm CMOS process with a 24-V high-voltage transistor option. Pulse-echo measurements are performed column-by-column in sequence using either one column or five columns to TX the ultrasonic pulse at 20 MHz. TX beamforming is used to focus the ultrasonic beam at the imaging plane where the finger is located, increasing the ultrasonic pressure and narrowing the 3-dB beamwidth to [Formula: see text], a factor of 6.4 narrower than nonbeamformed measurements. The surface of the sensor is coated with a poly-dimethylsiloxane (PDMS) layer to provide good acoustic impedance matching to skin. Scanning laser Doppler vibrometry of the PDMS surface was used to map the ultrasonic pressure field at the imaging surface, demonstrating the expected increase in pressure, and reduction in beamwidth. Imaging experiments were conducted using both PDMS phantoms and real fingerprints. The average image contrast is increased by a factor of 1.5 when beamforming is used.

Monolithic ultrasound fingerprint sensor.

This paper presents a 591×438-DPI ultrasonic fingerprint sensor. The sensor is based on a piezoelectric micromachined ultrasonic transducer (PMUT) array that is bonded at wafer-level to complementary metal oxide semiconductor (CMOS) signal processing electronics to produce a pulse-echo ultrasonic imager on a chip. To meet the 500-DPI standard for consumer fingerprint sensors, the PMUT pitch was reduced by approximately a factor of two relative to an earlier design. We conducted a systematic design study of the individual PMUT and array to achieve this scaling while maintaining a high fill-factor. The resulting 110×56-PMUT array, composed of 30×43-µm2 rectangular PMUTs, achieved a 51.7% fill-factor, three times greater than that of the previous design. Together with the custom CMOS ASIC, the sensor achieves 2 mV kPa-1 sensitivity, 15 kPa pressure output, 75 µm lateral resolution, and 150 µm axial resolution in a 4.6 mm×3.2 mm image. To the best of our knowledge, we have demonstrated the first MEMS ultrasonic fingerprint sensor capable of imaging epidermis and sub-surface layer fingerprints.