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Perovskite oxide has good sensitivity to VOCs gases, but its gas-sensitive properties are negatively affected by high humidity, thereby limiting its potential application in respiratory gas detection. This study focuses on synthesizing porous LaFeO 3 of perovskite type used a dual-process method involved hydrothermal synthesis with thermal treatment. The morphology and evolution of porous LaFeO 3 microspheres was studied. The LaFeO 3 sensors exhibited p-type gas-sensitive behavior with notable selectivity for respiratory gases. The LaFeO 3 sensor represented a significant response value of 9.7 to a 100 ppm C 2 H 5 OH concentration, with a rapid response/recovery time of 8 s/9 s at 300 °C. The sensor demonstrated a high response ( S  = 4.2) and a low detection limit of 100 ppb at 90% relative humidity. The superior sensor performance was due to the porous surface structure of LaFeO 3 microspheres, which improved the gas diffusion channels and reaction sites with microspheres. The density of states map revealed a strong orbital hybridization between C 2 H 5 OH and LaFeO 3 , resulted in a calculated adsorption energy of − 1.18 eV, signified a strong adsorption affinity in line with the experimental results. Graphical abstract

An optical receiver employs an all-inverter-based front-end design that provides maximum transconductance for a given power supply and allows for ultra-low power consumption. The feedback transimpedance amplifier (TIA) input stage utilizes a multi-stage amplifier to achieve a dramatic increase in feedback resistance and lower input-referred noise. Cascading an inverter-based active inductor continuous-time linear equalizer provides frequency peaking to compensate the input stage TIA that is intentionally designed with a reduced bandwidth to achieve adequate sensitivity at low power. Fabricated in 28 nm CMOS, the 12.5 Gb/s optical receiver achieves - 10.7 dBm OMA sensitivity at 0.11 pJ/bit energy efficiency and occupies only 720  μ m 2 area.

A single channel 1.5GS/s 8-bit pipelined-SAR ADC utilizes a novel output level shifting (OLS) settling technique to reduce the power and enable low-voltage operation of the dynamic residue amplifier. The ADC consists of a 4-bit first stage and a 5-bit second stage, with 1-bit redundancy to relax the offset, gain, and settling requirements of the first stage. Employing the OLS technique allows for an inter-stage gain of ~4 from the dynamic residue amplifier with a settling time that is only 28% of a conventional CML amplifier. The ADC's conversion speed is further improved with the use of parallel comparators in the two asynchronous stages. Fabricated in a 14nm FinFET technology, the ADC occupies 0.0013mm2 core area and operates with a 0.8V supply. 6.6-bit ENOB is achieved at Nyquist while consuming 2.4mW, resulting in an FOM of 16.7fJ/conv.-step.

While the majority of wireline research investigates bandwidth improvement and how to overcome the high channel loss, pin efficiency is also critical in high-performance wireline applications. This dissertation proposes two different implementations for high pin efficiency wireline transceivers. The first prototype achieves twice pin efficiency than unidirectional signaling, which is 32Gb/s simultaneous bidirectional transceiver supporting transmission and reception on the same channel at the same time. It includes an efficient low-swing voltage-mode driver with an R-gm hybrid for signal separation, combining the continuous-time-linear-equalizer (CTLE) and echo cancellation (EC) in a single stage, and employing a low-complexity 5/4X CDA system. Support of a wide range of channels is possible with foreground adaptation of the EC finite impulse response (FIR) filter taps with a sign-sign least-mean-square (SSLMS) algorithm. Fabricated in TSMC 28-nm CMOS, the 32Gb/s SBD transceiver occupies 0.09 mm2 area and achieves 16Gb/s uni-directional and 32Gb/s simultaneous bi-directional signals. 32Gb/s SBD operation consumes 1.83mW/Gb/s with 10.8dB channel loss at Nyquist rate. The second prototype presents an optical transmitter with a quantum-dot (QD) microring laser. This can support wavelength-division multiplexing allowing for high pin efficiency application by packing multiple high-bandwidth signals onto one optical channel. The development QD microring laser model accurately captures the intrinsic photonic high-speed dynamics and allows for the future co-design of the circuits and photonic device. To achieve higher bandwidth than intrinsic one, utilizing both techniques of optical injection locking (OIL) and 2-tap asymmetric Feed-forward equalizer (FFE) can perform 22Gb/s operation with 3.2mW/Gb/s. The first hybrid-integration directly-modulated OIL QD microring laser system is demonstrated.

There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 Å resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution. In this study, Qin et al. present a murine-adapted SARS-CoV-2 strain, MASCp36, as a model for studying the pathogenicity, evolution and adaptation of the virus to human and animal hosts.

A four-year-old boy developed recurrent fever and severe pneumonia in April, 2022. High-throughput sequencing revealed a reassortant avian influenza A-H3N8 virus (A/Henan/ZMD-22-2/2022(H3N8) with avian-origin HA and NA genes. The six internal genes were acquired from Eurasian lineage H9N2 viruses. Molecular substitutions analysis revealed the haemagglutin retained avian-like receptor binding specificity but that PB2 genes possessed sequence changes (E627K) associated with increased virulence and transmissibility in mammalian animal models. The patient developed respiratory failure, liver, renal, coagulation dysfunction and sepsis. Endotracheal intubation and extracorporeal membrane oxygenation were administered. H3N8 RNA was detected from nasopharyngeal swab of a dog, anal swab of a cat, and environmental samples collected in the patient’s house. The full-length HA sequences from the dog and cat were identical to the sequence from the patient. No influenza-like illness was developed and no H3N8 RNA was identified in family members. Serological testing revealed neutralizing antibody response against ZMD-22-2 virus in the patient and three family members. Our results suggest that a triple reassortant H3N8 caused severe human disease. There is some evidence of mammalian adaptation, possible via an intermediary mammalian species, but no evidence of person-to-person transmission. The potential threat from avian influenza viruses warrants continuous evaluation and mitigation. The H3N8 influenza virus is known to circulate in wild birds but cross-species transmission to mammalian hosts was also reported. In this case study, the authors report human infection with a reassortment avian influenza A H3N8 virus in a four-year old boy that developed severe symptoms.

A flavonoids-rich extract of Scutellaria baicalensis shoots and its eight high content flavonoids were investigated for their inhibitory effects against α-glucosidase and α-amylase. Results show that abilities of the extract in inhibiting the two enzymes were obviously higher than those of acarbose. Moreover, inhibitory abilities of all the eight individual flavonoids against the two enzymes show exactly a same order (i.e., apigenin > baicalein > scutellarin > chrysin > apigenin-7-O-glucuronide > baicalin > chrysin-7-O-glucuronide > isocarthamidin-7-O-glucuronide), and their structure–activity relationship could be well-interpretated by the refined assign-score method. Furthermore, based on the inhibitory abilities and their contents in the extract, it was found that the eight flavonoids made predominant contributions, among which baicalein and scutellarin played roles as preliminary contributors, to overall inhibitory effects of the extract against the two enzymes. Beyond these, contributions of the eight flavonoids to the overall enzyme inhibitory activity were compared with those to the overall antioxidant activity characterized in our recent study, and it could be inferred that within the basic flavonoid structure the hydroxyl on C-4′ of ring B was more effective than that on C-6 of ring A in enzyme inhibitory activities while they behaved inversely in antioxidant activities; scutellarin and apigenin contributed more to the overall enzyme inhibitory activity, and baicalin and scutellarin, to the overall antioxidant activity of the extract; and flavonoids of the extract, apart from directly inhibiting enzymes, might also be conducive to curing type 2 diabetes via scavenging various free radicals caused by increased oxidative stresses.

AimsProgesterone receptor (PR) is a crucial prognostic marker in breast cancer. However, achieving consistent results in PR immunohistochemistry (IHC) remains challenging due to the lack of well-defined low-positive controls. This study aimed to identify benign tissues with consistent low-level PR expression to serve as ideal controls for IHC.MethodsWe evaluated PR expression in the squamous epithelium of the uterine cervix, nipple smooth muscle and pancreatic islets. QuPath digital image analysis was employed to compare the intensity and quantity of PR staining in target cells within a 2×2 mm area.ResultsThe squamous epithelium of the secretory phase cervix, nipple smooth muscle and pancreatic islets displayed appreciable weak PR expression, with mean values of 73, 55 and 60 cells, respectively. Notably, 62% (8/13) of the 2×2 mm areas in the atrophic cervix were completely negative for PR expression. The coefficients of variation for weak PR-expressing cells in pancreatic islets (57.4%) and nipple smooth muscle (65.0%) were lower than those observed in the cervix (96.2%–222.0%). The squamous epithelium of the cervix, especially during the secretory phase, exhibited weak positivity confined to the basal layers, providing another viable control option. However, variations in PR expression may be influenced by physiological factors, such as hormonal fluctuations.ConclusionsPancreatic islets and nipple smooth muscle, with their consistent low-level PR expression, offer a promising solution to the challenges associated with PR IHC. This approach may help minimise variations resulting from differing staining methods across laboratories.

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne bunyavirus, causes mild-to-moderate infection to critical illness or even death in human patients. The effect of virus variations on virulence and related clinical significance is unclear. We prospectively recruited SFTSV-infected patients in a hotspot region of SFTS endemic in China from 2011 to 2020, sequenced whole genome of SFTSV, and assessed the association of virus genomic variants with clinical data, viremia, and inflammatory response. We identified seven viral clades (I-VII) based on phylogenetic characterization of 805 SFTSV genome sequences. A significantly increased case fatality rate (32.9%) was revealed in one unique clade (IV) that possesses a specific co-mutation pattern, compared to other three common clades (I, 16.7%; II, 13.8%; and III, 11.8%). The phenotype-genotype association (hazard ratios ranged 1.327-2.916) was confirmed by multivariate regression adjusting age, sex, and hospitalization delay. We revealed a pronounced inflammation response featured by more production of CXCL9, IL-10, IL-6, IP-10, M-CSF, and IL-1β, in clade IV, which was also related to severe complications. We observed enhanced cytokine expression from clade IV inoculated PBMCs and infected mice. Moreover, the neutralization activity of convalescent serum from patients infected with one specified clade was remarkably reduced to other viral clades. Together, our findings revealed a significant association between one specific viral clade and SFTS fatality, highlighting the need for molecular surveillance for highly lethal strains in endemic regions and unravelled the importance of evaluating cross-clade effect in development of vaccines and therapeutics.

This study is the first to report the use of response surface methodology to improve phenolic yield and antioxidant activity of Acer truncatum leaves extracts (ATLs) obtained by ultrasonic-assisted extraction. The phenolic composition in ATLs extracted under the optimized conditions were characterized by UPLC-QTOF-MS/MS. Solvent and extraction time were selected based on preliminary experiments, and a four-factors-three-levels central composite design was conducted to optimize solvent concentration (X1), material-to-liquid ratio (X2), ultrasonic temperature (X3) and power (X4) for an optimal total phenol yield (Y1) and DPPH• antioxidant activity (Y2). The results showed that the optimal combination was ethanol:water (v:v) 66.21%, material-to-liquid ratio 1:15.31 g/mL, ultrasonic bath temperature 60 °C, power 267.30 W, and time 30 min with three extractions, giving a maximal total phenol yield of 7593.62 mg gallic acid equivalent/100 g d.w. and a maximal DPPH• antioxidant activity of 74,241.61 μmol Trolox equivalent/100 g d.w. Furthermore, 22 phenolics were first identified in ATL extract obtained under the optimized conditions, indicating that gallates, gallotannins, quercetin, myricetin and chlorogenic acid derivatives were the main phenolic components in ATL. What’s more, a gallotannins pathway existing in ATL from gallic acid to penta-O-galloylglucoside was proposed. All these results provide practical information aiming at full utilization of phenolics in ATL, together with fundamental knowledge for further research.