Correcting PCR amplification errors in unique molecular identifiers to generate accurate numbers of sequencing molecules.

Unique molecular identifiers are random oligonucleotide sequences that remove PCR amplification biases. However, the impact that PCR associated sequencing errors have on the accuracy of generating absolute counts of RNA molecules is underappreciated. We show that PCR errors are a source of inaccuracy in both bulk and single-cell sequencing data, and synthesizing unique molecular identifiers using homotrimeric nucleotide blocks provides an error-correcting solution that allows absolute counting of sequenced molecules.

TMKit: a Python interface for computational analysis of transmembrane proteins.

Transmembrane proteins are receptors, enzymes, transporters and ion channels that are instrumental in regulating a variety of cellular activities, such as signal transduction and cell communication. Despite tremendous progress in computational capacities to support protein research, there is still a significant gap in the availability of specialized computational analysis toolkits for transmembrane protein research. Here, we introduce TMKit, an open-source Python programming interface that is modular, scalable and specifically designed for processing transmembrane protein data. TMKit is a one-stop computational analysis tool for transmembrane proteins, enabling users to perform database wrangling, engineer features at the mutational, domain and topological levels, and visualize protein-protein interaction interfaces. In addition, TMKit includes seqNetRR, a high-performance computing library that allows customized construction of a large number of residue connections. This library is particularly well suited for assigning correlation matrix-based features at a fast speed. TMKit should serve as a useful tool for researchers in assisting the study of transmembrane protein sequences and structures. TMKit is publicly available through https://github.com/2003100127/tmkit and https://tmkit-guide.herokuapp.com/doc/overview.

Broadband free space 2 × 4 90° optical hybrid for satellite laser communication.

We design a broadband free space 2×4 90° optical hybrid over a spectral window of 1000-1200 nm and 1470-1650 nm and verify the feasibility of the scheme experimentally. The hybrid consists of three broadband polarization beam splitters, an achromatic λ/4 wave plate, and three achromatic λ/2 wave plates. The fabricated hybrid exhibits a good quadrature phase response with an interchannel imbalance of 0.93-1.07 and a low phase deviation of less than 0.2° under the typical communication wavelengths of 1064 nm and C-band. The experimental results of the heterodyne method show that the proposed hybrid can effectively solve the wavelength incompatibility problem in satellite laser communication and realize interconnection at different wavelengths. The designed hybrid (without coupling) has a measured insertion loss of no more than 7.34 dB at 1064 nm and C-band. A high-speed transmission experiment with BPSK format has been conducted to verify the performance of the assembled device.

Role and molecular mechanism of ghrelin in degenerative musculoskeletal disorders.

Ghrelin is a brain-gut peptide, and the first 28-peptide that was found in the gastric mucosa. It has a growth hormone (GH)-releasing hormone-like effect and can potently promote the release of GH from pituitary GH cells; however, it is unable to stimulate GH synthesis. Therefore, ghrelin is believed to play a role in promoting bone growth and development. The correlation between ghrelin and some degenerative diseases of the musculoskeletal system has been reported recently, and ghrelin may be one of the factors influencing degenerative pathologies, such as osteoporosis, osteoarthritis, sarcopenia and intervertebral disc degeneration. With population ageing, the risk of health problems caused by degenerative diseases of the musculoskeletal system gradually increases. In this article, the roles of ghrelin in musculoskeletal disorders are summarized to reveal the potential effects of ghrelin as a key target in the treatment of related bone and muscle diseases and the need for further research.

Selective Chemical Labeling Strategy for Oligonucleotides Determination: A First Application to Full-Range Profiling of Transfer RNA Modifications.

To date, the extremely high polarity and poor signal intensity of macromolecular nucleic acids are greatly impeding the progress of mass spectrometry technology in the quality control of nucleic acid drugs and the characterization of DNA oxidation and RNA modifications. We recently described a general N-(tert-butyldimethylsilyl)-N-methyl-trifluoroacetamide (MTBSTFA) labeling method for oligonucleotide determination and applied it to the full-range profiling of tRNA in vitro and in vivo studies for the first time. The primary advantages of this method include strong retention, no observable byproducts, predictable and easily interpreted MS2 data, and the circumvention of instrument harmful reagents that were necessary in previous methods. Selective labeling of N-(tert-butyldimethylsilyl)-N-methyl-trifluoroacetamide to the terminal phosphate groups of oligonucleotides endows it broadly applicable for DNA/RNA profiling. Moreover, the improvement of sequence coverage was achieved in yeast tRNAphe(GAA) analysis owing to this method's good detection capability of 1-12 nucleotides in length. We also extended this strategy to determine the abundance of modified bases and discover new modifications via digesting RNA into single-nucleotide products, promoting the comprehensive mapping of RNA. The easy availability of derivatization reagent and the simple, rapid one-step reaction render it easy to operate for researchers. When applied in characterizing tRNAs in HepG2 cells and rats with nonalcoholic fatty liver disease, a fragment of U[m1G][m2G], specific for tRNAAsn(QUU) in cells, was significantly upregulated, indicating a possible clue to nonalcoholic fatty liver disease pathogenesis.

Scale-adaptive three-dimensional imaging using Risley-prism-based coherent lidar.

We present a scale-adaptive three-dimensional (3D) imaging architecture for coherent light detection and ranging (lidar) that incorporates Risley-prism-based beam scanning. An inverse design paradigm from beam steering to prism rotation is developed for demand-oriented beam scan pattern generation and prism motion law formulation, which allows the lidar to perform 3D imaging with adaptive scale and configurable resolution. By combining flexible beam manipulation with simultaneous distance and velocity measurement, the proposed architecture can achieve both large-scale scene reconstruction for situational awareness and small-scale object identification against long range. The experiment results demonstrate that our architecture enables the lidar to recover a 3D scene in a ±30° field of view and also focus on distant objects at over 500 m with spatial resolution up to 1.1 cm.

In-Plane Rotation of Prolate Colloids Adhered to a Planar Substrate in the Presence of Flow.

Micron-size spherical polystyrene colloidal particles are mechanically stretched to a prolate geometry with desirable aspect ratios. The particles in an aqueous medium with specific ionic concentration are then introduced into a microchannel and allowed to settle on a glass substrate. In the presence of unidirectional flow, the loosely adhered particles in the secondary minimum of surface interaction potential are easily washed off, but the remnant in the strong primary minimum preferentially aligns with the flow direction and exercises in-plane rotation. A rigorous theoretical model is constructed to account for filtration efficiency in terms of hydrodynamic drag, intersurface forces, reorientation of prolate particles, and their dependence on flowrate and ionic concentration.

Tea leaf-derived exosome-like nanotherapeutics retard breast tumor growth by pro-apoptosis and microbiota modulation.

While several artificial nanodrugs have been approved for clinical treatment of breast tumor, their long-term applications are restricted by unsatisfactory therapeutic outcomes, side reactions and high costs. Conversely, edible plant-derived natural nanotherapeutics (NTs) are source-widespread and cost-effective, which have been shown remarkably effective in disease treatment. Herein, we extracted and purified exosome-like NTs from tea leaves (TLNTs), which had an average diameter of 166.9 nm and a negative-charged surface of - 28.8 mV. These TLNTs contained an adequate slew of functional components such as lipids, proteins and pharmacologically active molecules. In vitro studies indicated that TLNTs were effectively internalized by breast tumor cells (4T1 cells) and caused a 2.5-fold increase in the amount of intracellular reactive oxygen species (ROS) after incubation for 8 h. The high levels of ROS triggered mitochondrial damages and arrested cell cycles, resulting in the apoptosis of tumor cells. The mouse experiments revealed that TLNTs achieved good therapeutic effects against breast tumors regardless of intravenous injection and oral administration through direct pro-apoptosis and microbiota modulation. Strikingly, the intravenous injection of TLNTs, not oral administration, yielded obvious hepatorenal toxicity and immune activation. These findings collectively demonstrate that TLNTs can be developed as a promising oral therapeutic platform for the treatment of breast cancer.

Physician-Modified Endovascular Graft for Left Subclavian Artery Fenestration during Thoracic Endovascular Aortic Repair.

BACKGROUND: This study aimed to evaluate the safety and efficacy of physician-modified endovascular graft for preservation of left subclavian artery during thoracic endovascular aortic repair. METHODS: From June 2019 to October 2022, 66 patients with a variety of thoracic aortic pathologies were treated with thoracic endovascular aortic repair using physician-modified endovascular graft left subclavian artery fenestration to achieve adequate proximal landing zone. The details of surgical techniques were described. The perioperative morbidity, mortality, and the outcomes of mid-term follow-up were analyzed. RESULTS: Of the 66 patients (men: women, 53:13; age, 55.18 [55.18 ± 10.62] years), 53 (80.30%) presented with type B aortic dissection, 10 (15.15%) with thoracic penetrating aortic ulcer, 2 (3.03%) with thoracic aortic aneurysm, and 1 (1.52%) with left subclavian artery aneurysm. All of them underwent thoracic endovascular aortic repair using physician-modified endovascular graft left subclavian artery fenestration on the sterile back table. The technique success rate was 96.97% (n = 64). Total operation time was 92 min (interquartile range, 86-118), graft modification time was 19 min (interquartile range, 17-21), fluoroscopy time was 49 min (interquartile range, 41-62), and contrast agent dosage was 165 mL (interquartile range, 155-185). 30-day perioperative morbidities were 3 (4.55%) strokes, 1 (1.52%) retrograde type A aortic dissection, 1 (1.52%) aortic intimal intussusception, 1 (1.52%) left arm ischemia, and 3 (4.55%) type Ia endoleaks. Postoperative 30-day mortality and reintervention rates were 1.52% and 4.55%, respectively. Among the 63 patients included in the follow-up of 17 months (interquartile range, 7.75-18.25), the primary patency of left subclavian artery fenestration stents was 100%. Late complications were 1 (1.59%) distal stent graft-induced new entry and 1 (1.59%) death due to retrograde type A aortic dissection during the follow-up. The stent graft-induced new entry patient was observed with stable false lumen. CONCLUSIONS: Thoracic endovascular aortic repair with physician-modified endovascular graft for left subclavian artery revascularization is a safe, feasible, and efficacious technique associated with high success rate. Further study is needed for long-term outcome investigation.

Real-time acquisition and enhancement of remote acoustic signals by a free-space monostatic homodyne laser Doppler vibrometer.

This paper systematically presents the design and performance of an extremely sensitive 1.55-µm free-space monostatic laser Doppler vibrometer (LDV) using optical homodyne detection for real-time acquisition and enhancement of the remote acoustic signals. The phase shifts produced by laser light scattered off a remote target carries the extremely tiny vibration displacement information of the target' surface motivated by the acoustic source around and is demodulated using the optical in-phase/quadrature demodulator. The real-time acquisitions of the remote acoustic signals, including the sinusoidal signal and the speech signal at the target distance of 100 m, is performed between two buildings. The real-time speech enhancement of remote speech signals is also carried out by the different algorithms based on the short-time spectral magnitude, and the comprehensible speech signals can be reconstructed. The results demonstrate that the designed free-space monostatic homodyne LDV has a low system background noise and can offer high precision for the uncooperative targets in the real-time acquisition of the remote acoustic signal.

Sensitivity Deterioration of Free-Space Optical Coherent/Non-Coherent OOK Modulation Receiver by Ambient Light Noise.

In free-space optical (FSO) communication systems, on-off keying (OOK) is a widely used modulation format. Coherent and non-coherent OOK receivers with sensitivities of -54.60 dBm and -51.25 dBm, respectively, were built with a communication rate of 1 Gbit/s and a bit error rate of 10-3. In an FSO communication system, the parameters must be designed to ensure a sufficient link margin. In contrast to optical fiber systems, FSO systems have ambient light (AL) noise such as sunlight. The efficiency of sunlight coupling in the single-mode fiber (SMF) of the receivers was calculated in this study. For a signal light with AL, the change in the main components of noise and the sensitivity deterioration were theoretically analyzed and experimentally verified in conditions of coherent reception and non-coherent reception with a preamplifier. For coherent reception, the theoretical sensitivity deterioration results are consistent with the experimental results which indicate that coherent reception exhibits better anti-AL noise performance than non-coherent reception when the power spectral density of the AL is the same. Coherent and non-coherent receivers coupled with SMF can work in direct sunlight. When the receiver lens diameter is greater than 4.88 × 10-4 m, the anti-AL noise performance of the receiver can be improved by increasing the receiver lens diameter.

Efficient Fault Detection of Rotor Minor Inter-Turn Short Circuit in Induction Machines Using Wavelet Transform and Empirical Mode Decomposition.

This paper introduces a novel approach for detecting inter-turn short-circuit faults in rotor windings using wavelet transformation and empirical mode decomposition. A MATLAB/Simulink model is developed based on electrical parameters to simulate the inter-turn short circuit by adding a resistor parallel to phase "a" of the rotor. The resulting high current in the new phase indicates the presence of the short circuit. By measuring the rotor and stator three-phase currents, the fault can be detected as the currents exhibit asymmetric behavior. Fluctuations in the electromagnetic torque also occur during the fault. The wavelet transform is applied to the rotor current, revealing an effective analysis of sideband frequency components. Specifically, changes in amplitude and frequency, particularly in d7 and a7, indicate the presence of harmonics generated by the inter-turn short circuit. The simulation results demonstrate the effectiveness of wavelet transformation in analyzing these frequency components. Additionally, this study explores the use of empirical mode decomposition to detect faults in their early stages, observing substantial changes in the instantaneous amplitudes of the first three intrinsic mode functions during fault onset. The proposed technique is straightforward and reliable, making it suitable for application in wind turbines with simple electrical inputs.

DeepsmirUD: Prediction of Regulatory Effects on microRNA Expression Mediated by Small Molecules Using Deep Learning.

Aberrant miRNA expression has been associated with a large number of human diseases. Therefore, targeting miRNAs to regulate their expression levels has become an important therapy against diseases that stem from the dysfunction of pathways regulated by miRNAs. In recent years, small molecules have demonstrated enormous potential as drugs to regulate miRNA expression (i.e., SM-miR). A clear understanding of the mechanism of action of small molecules on the upregulation and downregulation of miRNA expression allows precise diagnosis and treatment of oncogenic pathways. However, outside of a slow and costly process of experimental determination, computational strategies to assist this on an ad hoc basis have yet to be formulated. In this work, we developed, to the best of our knowledge, the first cross-platform prediction tool, DeepsmirUD, to infer small-molecule-mediated regulatory effects on miRNA expression (i.e., upregulation or downregulation). This method is powered by 12 cutting-edge deep-learning frameworks and achieved AUC values of 0.843/0.984 and AUCPR values of 0.866/0.992 on two independent test datasets. With a complementarily constructed network inference approach based on similarity, we report a significantly improved accuracy of 0.813 in determining the regulatory effects of nearly 650 associated SM-miR relations, each formed with either novel small molecule or novel miRNA. By further integrating miRNA-cancer relationships, we established a database of potential pharmaceutical drugs from 1343 small molecules for 107 cancer diseases to understand the drug mechanisms of action and offer novel insight into drug repositioning. Furthermore, we have employed DeepsmirUD to predict the regulatory effects of a large number of high-confidence associated SM-miR relations. Taken together, our method shows promise to accelerate the development of potential miRNA targets and small molecule drugs.

Oral Nanomotor-Enabled Mucus Traverse and Tumor Penetration for Targeted Chemo-Sono-Immunotherapy against Colon Cancer.

The therapeutic outcomes of oral nanomedicines against colon cancer are heavily compromised by their lack of specific penetration into the internal tumor, favorable anti-tumor activity, and activation of anti-tumor immunity. Herein, hydrogen peroxide (H2 O2 )/ultrasound (US)-driven mesoporous manganese oxide (MnOx )-based nanomotors are constructed by loading mitochondrial sonosensitizers into their mesoporous channels and orderly dual-functionalizing their surface with silk fibroin and chondroitin sulfate. The locomotory activities and tumor-targeting capacities of the resultant nanomotors (CS-ID@NMs) are greatly improved in the presence of H2 O2 and US irradiation, inducing efficient mucus-traversing and deep tumor penetration. The excess H2 O2 in the tumor microenvironment (TME) is decomposed into hydroxyl radicals and oxygen by an Mn2+ -mediated Fenton-like reaction, and the produced oxygen participates in sonodynamic therapy (SDT), yielding abundant singlet oxygen. The combined Mn2+ -mediated chemodynamic therapy and SDT cause effective ferropotosis of tumor cells and accelerate the release of tumor antigens. Importantly, animal experiments reveal that the treatment of combining oral hydrogel (chitosan/alginate)-embedding CS-ID@NMs and immune checkpoint inhibitors can simultaneously suppress the growth of primary and distal tumors through direct killing, reversion of immunosuppressive TME, and potentiation of systemic anti-tumor immunity, demonstrating that the CS-ID@NM-based platform is a robust oral system for synergistic treatment of colon cancer.

Multi-dimensional and large-sized optical phased array for space laser communication.

In this study, we propose a novel multi-dimensional and large-sized optical phased array theory for space laser communication that addresses the theoretical limitations of the conventional optical phased array. We theoretically analyzed the principle of this phased array technology. The results of simulation and laboratory experiment clearly showed it can realize the large scanning angle and high optical gain required for communication. The novel optical phased array theory is of great significance to the revolution of miniaturization and networking in the field of space laser communication.

Three-dimensional single-photon imaging through realistic fog in an outdoor environment during the day.

Due to the strong scattering of fog and the strong background noise, the signal-to-background ratio (SBR) is extremely low, which severely limits the 3D imaging capability of single-photon detector array through fog. Here, we propose an outdoor three-dimensional imaging algorithm through fog, which can separate signal photons from non-signal photons (scattering and noise photons) with SBR as low as 0.003. This is achieved by using the observation model based on multinomial distribution to compensate for the pile-up, and using dual-Gamma estimation to eliminate non-signal photons. We show that the proposed algorithm enables accurate 3D imaging of 1.4 km in the visibility of 1.7 km. Compared with the traditional algorithms, the target recovery (TR) of the reconstructed image is improved by 20.5%, and the relative average ranging error (RARE) is reduced by 28.2%. It has been successfully demonstrated for targets at different distances and imaging times. This research successfully expands the fog scattering estimation model from indoor to outdoor environment, and improves the weather adaptability of the single-photon detector array.

Dual-controlled tunable dual-band and ultra-broadband coherent perfect absorber in the THz range.

This paper proposes a vanadium dioxide metamaterial-based tunable, polarization-independent coherent perfect absorber (CPA) in the terahertz frequency range. The designed CPA demonstrates intelligent reconfigurable switch modulation from an ultra-broadband absorber mode to a dual-band absorber mode via the thermally controlled of VO2. The mode of ultra-broadband absorber is realized when the conductivity of VO2 reaches 11850 S/m via controlling its temperature around T = 328 K. In this mode, the CPA demonstrates more than 90% absorption efficiency within the ultra-wide frequency band that extends from 0.1 THz to 10.8 THz. As the conductivity of VO2 reaches 2×105 S/m (T = 340 K), the CPA switches to a dual-band absorber mode where a relatively high absorption efficiency of 98% and 99.7% is detected at frequencies of 4.5 THz and 9.8 THz, respectively. Additionally, using phase modulation of the incident light, the proposed CPA can regulate the absorption efficiency, which can be intelligently controlled from perfect absorption to high pass-through transmission. Owing to the ability of the proposed CPA to intelligently control the performance of light, this study can contribute towards enhancing the performance of stealth devices, all-optical switches and coherent photodetectors.

All-fiber low-frequency shifter based on acousto-optic interaction and its heterodyne vibration response.

We demonstrate two all-fiber low-frequency shift schemes based on the acousto-optic interaction in a few-mode fiber (FMF). Two acoustically induced fiber gratings (AIFGs) are cascaded in reverse to achieve an efficient cycle conversion between LP11 and LP01 core modes in the FMF while obtaining a frequency shift of 1.8 MHz. In addition, a long-period fiber grating (LPFG) is employed to replace the AIFG, which achieves a lower frequency shift of 0.9 MHz, and its tunable wavelength range exceeds 100 nm. Both schemes show the characteristics of an upward frequency shift. Moreover, we also present a heterodyne detection system based on the above frequency shift schemes, which is verified in response to micro-vibration signals ranging from tens to hundreds of kilohertz, as well as speech signals in a lower frequency range. The experimental results show that these all-fiber frequency shift schemes have potential applications, such as in fiber optic hydrophones, laser speech detection, and fiber optic sensors.

Role of magnesium-doped calcium sulfate and ß-tricalcium phosphate composite ceramics in macrophage polarization and osteo-induction.

In the current study, we explored the role of Mg2+-doped CaSO4/ß-TCP composite biopolymer in regulating macrophage polarization and its relation with enhanced osteogenic differentiation of periodontal ligament stem cells. Furthermore, mechanism underling the regulation of macrophage polarization by CaSO4/ß-TCP was evaluated. Mg2+-doped CaSO4/ß-TCP composite was characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Macrophage polarization was characterized using flow cytometry analysis. Macrophage morphometric analysis was conducted by FITC phalloidin staining. Western blot and qRT-PCR assays were used to assess gene expression levels and miRNAs, respectively. SEM morphology of CaSO4/ß-TCP ceramic revealed a particle size of 10-50 µm, and XRD spectrum showed that characteristic peak of samples was consistent with that of CaSO4 and ß-TCP. Results from flow cytometry evidenced significant upregulation of M2 macrophage markers after adding ceramic biopolymer, indicating the induction of inactivated M0 macrophage polarization to M2 macrophage. Macrophage morphometric analysis revealed development of lamellar pseudopodia on day 7 in CaSO4/ß-TCP group. Furthermore, flow cytometry revealed high positivity rate of 90.34% (CD44) and 89.36% (CD146). qRT-PCR results showed that the level of miR-21-5p was significantly decreased in M2 macrophages. Moreover, western blot analysis revealed upregulated expression levels of RUNX2, osterix (Osx), and osteopontin (OPN), and ELISA exhibited increase in cytokine levels (IL-1ß, IL-10, TGF-ß1, and BMP-2) in the presence of macrophages, indicating the osteogenic differentiation ability of periodontal ligament stem cells. The study evidenced the regulation of macrophage polarization by Mg2+-doped CaSO4/ß-TCP composite ceramic and its mediation through lncRNA PVT1/miR-21-5p/smad2 molecular axis.

Comparison of Venous Thromboembolism Risks Between COVID-19 Pneumonia and Community-Acquired Pneumonia Patients.

OBJECTIVE: The objectives were to investigate and compare the risks and incidences of venous thromboembolism (VTE) between the 2 groups of patients with coronavirus disease 2019 (COVID-19) pneumonia and community-acquired pneumonia (CAP). Approach and Results: Medical records of 616 pneumonia patients who were admitted to the Yichang Central People's Hospital in Hubei, China, from January 1 to March 23, 2020, were retrospectively reviewed. The patients with COVID-19 pneumonia were treated in the dedicated COVID-19 units, and the patients with CAP were admitted to regular hospital campus. Risks of VTE were assessed using the Padua prediction score. All the patients received pharmaceutical or mechanical VTE prophylaxis. VTE was diagnosed using Duplex ultrasound or computed tomography pulmonary angiogram. Differences between COVID-19 and CAP groups were compared statistically. All statistical tests were 2 sided, and P<0.05 was considered as statistically significant. All data managements and analyses were performed by IBM SPSS, version 24, software (SPSS, Inc, Chicago, IL). Of the 616 patients, 256 had COVID-19 pneumonia and 360 patients had CAP. The overall rate of VTE was 2% in COVID-19 pneumonia group and 3.6% in CAP group, respectively (P=0.229). In these two groups, 15.6% of the COVID-19 pneumonia patients and 10% of the CAP patients were categorized as high risk for VTE (Padua score, >4), which were significantly different (P=0.036). In those high-risk patients, the incidence of VTE was 12.5% in COVID-19 pneumonia group and 16.7% in CAP group (P=0.606). Subgroup analysis of the critically ill patients showed that VTE rate was 6.7% in COVID-19 group versus 13% in CAP group (P=0.484). In-hospital mortality of COVID-19 and CAP was 6.3% and 3.9%, respectively (P=0.180). CONCLUSIONS: Our study suggested that COVID-19 pneumonia was associated with hypercoagulable state. However, the rate of VTE in COVID-19 pneumonia patients was not significantly higher than that in CAP patients.