Catalytic divergent synthesis of imidazoles via reaction condition-dependent [3 + 2] cyclization of TosMIC.

A base-catalyzed divergent synthesis of multisubstituted imidazoles through TosMIC-based [3 + 2] cyclization reaction has been developed. In the presence of ketenimines and tBuONa, 1,4,5-trisubstituted imidazoles were obtained. Nonetheless, in the absence of ketenimines, 1,4-disubstituted imidazole was produced through cyclodimerization of TosMIC.

Therapeutic apheresis in kidney diseases: an updated review.

Besides conventional medical therapies, therapeutic apheresis has become an important adjunctive or alternative therapeutic option to immunosuppressive agents for primary or secondary kidney diseases and kidney transplantation. The available therapeutic apheresis techniques used in kidney diseases, including plasma exchange, double-filtration plasmapheresis, immunoadsorption, and low-density lipoprotein apheresis. Plasma exchange is still the leading extracorporeal therapy. Recently, growing evidence supports the potential benefits of double-filtration plasmapheresis and immunoadsorption for more specific and effective clearance of pathogenic antibodies with fewer side effects. However, more randomized controlled trials are still needed. Low-density lipoprotein apheresis is also an important supplementary therapy used in patients with recurrent focal segmental glomerulosclerosis. This review collects the latest evidence from recent studies, focuses on the specific advantages and disadvantages of these techniques, and compares the discrepancy among them to determine the optimal therapeutic regimens for certain kidney diseases.

Recent Advances in the Emerging Therapeutic Strategies for Diabetic Kidney Diseases.

Diabetic kidney disease (DKD) is one of the most common causes of end-stage renal disease worldwide. The treatment of DKD is strongly associated with clinical outcomes in patients with diabetes mellitus. Traditional therapeutic strategies focus on the control of major risk factors, such as blood glucose, blood lipids, and blood pressure. Renin-angiotensin-aldosterone system inhibitors have been the main therapeutic measures in the past, but the emergence of sodium-glucose cotransporter 2 inhibitors, incretin mimetics, and endothelin-1 receptor antagonists has provided more options for the management of DKD. Simultaneously, with advances in research on the pathogenesis of DKD, some new therapies targeting renal inflammation, fibrosis, and oxidative stress have gradually entered clinical application. In addition, some recently discovered therapeutic targets and signaling pathways, mainly in preclinical and early clinical trial stages, are expected to provide benefits for patients with DKD in the future. This review summarizes the traditional treatments and emerging management options for DKD, demonstrating recent advances in the therapeutic strategies for DKD.

PAM4 rolling-shutter demodulation using a pixel-per-symbol labeling neural network for optical camera communications.

The typical optical camera communication (OCC) modulation scheme is based on binary intensity modulation. To increase the transmission data rate, multi-level modulation format is highly desirable. In this work, we bring forward and demonstrate a rolling shutter 4-level pulse amplitude modulation (PAM4) demodulation scheme for OCC systems using pixel-per-symbol labeling neural network (PPSL-NN) for the first time up to the authors' knowledge. A bit-rate distance product of 28.8 kbit/s • m per color is achieved. The proposed scheme is to calculate and re-sample the pixel-per-symbol (PPS) to make sure the same number of pixels in each PAM4 symbol is corresponding to a label for the neural network. Experiment results reveal that the proposed scheme can efficiently demodulate high speed PAM4 signal in the rolling shutter OCC pattern.

Employing DIALux to relieve machine-learning training data collection when designing indoor positioning systems.

We propose and demonstrate using the DIALux software with our proposed linear-regression machine-learning (LRML) algorithm for designing a practical indoor visible light positioning (VLP) system. Experimental results reveal that the average position errors and error distributions of the model trained via the DIALux simulation and trained via the experimental data match with each other. This implies that the training data can be generated in DIALux if the room dimensions and LED luminary parameters are available. The proposed scheme could relieve the burden of training data collection in VLP systems.

Rolling-shutter-effect camera-based visible light communication using RGB channel separation and an artificial neural network.

We propose and demonstrate a light-panel and rolling-shutter-effect (RSE) camera-based visible light communication (VLC) system using Z-score normalization, red/green/blue (RGB) color channel separation, and 1-D artificial neural network (ANN). The proposed scheme can mitigate the high inter-symbol interference (ISI) generated by the RSE pattern due to the low pixel-per-bit and high noise-ratio (NR) of the display contents.

CMOS camera based visible light communication (VLC) using grayscale value distribution and machine learning algorithm.

We demonstrate a visible light communication (VLC) system using light emitting diode (LED) backlight display panel and mobile-phone complementary-metal-oxide-semiconductor (CMOS) camera. The panel is primarily used for displaying advertisements. By modulating its backlight, dynamic contents (i.e. secondary information) can be transmitted wirelessly to users based on rolling shutter effect (RSE) of the CMOS camera. As different display content will be displayed on the panel, the VLC performance is significantly limited if the noise-ratio (NR) is too high. Here, we propose and demonstrate a CMOS RSE pattern demodulation scheme using grayscale value distribution (GVD) and machine learning algorithm (MLA) to significantly enhance the demodulation.

Using logistic regression classification for mitigating high noise-ratio advisement light-panel in rolling-shutter based visible light communications.

We propose and experimentally demonstrated a light-panel and image sensor based visible light communication (VLC) system using machine learning (ML) algorithm. The ML algorithm is compared with the traditional demodulation scheme and the experimental results show that even at very high noise-ratio (NR) light-panel display content, the proposed ML algorithm shows significant bit error rate (BER) improvement.

Mitigation of performance degradation due to dynamic display contents in visible light communication using TV backlight and CMOS image sensor.

Here, we propose and demonstrate a performance degradation mitigation scheme in TV backlight and smart-phone-based visible light communication (VLC) system when the display content in the light-panel is dynamically changing. In order to evaluate the influence of the dynamic display contents to the VLC performance, we use a noise-ratio (NR) and noise-ratio standard deviation (NRSD) as the figure-of-merits for the bright-and-dark contrast of the display content; and the dispersal of the changing display content regarding the bright-and-dark contrast respectively. Performances of 4 dynamic display contents with different combinations of NR and NRSD are analyzed. They are: low NR and low NRSD (NR = 36.69%; NRSD = 0.0226); low NR and high NRSD (NR = 30.09%; NRSD = 0.2698); high NR and low NRSD (NR = 81.66%; NRSD = 0.0052); high NR and high NRSD (NR = 73.91%; and NRSD = 0.2717). The proposed scheme can work well; that is, even the transmission distance is up to 200 cm in both smart-phones. If the proposed scheme is not used, then high success rate can be observed only at the low NR and low NRSD display content when the transmission distance is < 100 cm.

Using advertisement light-panel and CMOS image sensor with frequency-shift-keying for visible light communication.

A frequency-shift-keying (FSK) visible light communication (VLC) system is proposed and demonstrated using advertisement light-panel as transmitter and mobile-phone image sensor as receiver. The developed application program (APP) in mobile-phone can retrieve the rolling shutter effect (RSE) pattern produced by the FSK VLC signal effectively. Here, we also define noise-ratio value (NRV) to evaluate the contrast of different advertisements displayed on the light-panel. Both mobile-phones under test can achieve success rate > 96% even when the transmission distance is up to 200 cm and the NRVs are low.

Revolutionizing nephrology research: expanding horizons with kidney-on-a-chip and beyond.

Organs-on-a-chip (OoC) is a microengineered three-dimensional cell culture system developed for decades. Utilizing microfluidic technology, OoC cultivates cells on perfusable channels to construct in vitro organ models, enabling the simulation of organ-level functions under physiological and pathophysiological conditions. The superior simulation capabilities compared to traditional animal experiments and two-dimensional cell cultures, making OoC a valuable tool for in vitro research. Recently, the application of OoC has extended to the field of nephrology, where it replicates various functional units, including glomerulus-on-a-chip, proximal tubule-on-a-chip, distal tubule-on-a-chip, collecting duct-on-a-chip, and even the entire nephron-on-a-chip to precisely emulate the structure and function of nephrons. Moreover, researchers have integrated kidney models into multi-organ systems, establishing human body-on-a-chip platforms. In this review, the diverse functional kidney units-on-a-chip and their versatile applications are outlined, such as drug nephrotoxicity screening, renal development studies, and investigations into the pathophysiological mechanisms of kidney diseases. The inherent advantages and current limitations of these OoC models are also examined. Finally, the synergy of kidney-on-a-chip with other emerging biomedical technologies are explored, such as bioengineered kidney and bioprinting, and a new insight for chip-based renal replacement therapy in the future are prospected.

Perspective of Calcium Imaging Technology Applied to Acupuncture Research.

Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.

Clinical characteristics and removal approaches of tracheal and bronchial foreign bodies in elders.

The symptoms of tracheobronchial foreign body in the elderly are not typical, so they are often missed or misdiagnosed. This study aims to depict the clinical characteristics of tracheobronchial foreign body inhalation in the elderly. We retrospectively analysed the clinical data of elder patients (age ≥ 65 years) diagnosed with tracheal and bronchial foreign bodies. The data included age, sex, clinical symptoms, type and location of foreign bodies, prehospital duration, Chest CT, bronchoscopic findings, and frequencies and tools for removing these elderly patients' tracheal and bronchial foreign bodies. All patients were followed up for a half year. Fifty-nine cases were included, of which only 32.2% had a definite aspiration history. Disease duration > 30 days accounted for 27.1% of the patients. 27.1% of the patients had a history of stroke, and 23.8% had Alzheimer's Disease. Regarding clinical symptoms, patients mainly experience cough and expectoration. The most common CT findings were abnormal density shadow (37.3%) and pulmonary infiltration (22.0%). Under bronchoscopy, purulent secretions were observed in 52.5% of patients, and granulation tissue hyperplasia was observed in 45.8%. Food (55.9%) was the most common foreign object, including seafood shells (5.1%), bones (20.3%), dentures (18.6%), and tablets (20.3%). The success rate of foreign body removal under a bronchoscope was 96.7%, 28.8% of the foreign bodies were on the left and 69.5% on the right. 5.1% of the elderly patients required rigid bronchoscopy, and 6.8% required two bronchoscopies. In elderly cohorts, tracheal foreign bodies are obscured by nonspecific clinical presentations and a paucity of aspiration history, challenging timely diagnosis. Predominantly constituted by food particles, with a notable predilection for the left bronchial tree, these cases demand skilled bronchoscopic management, occasionally requiring sophisticated approaches for successful extraction.

Sepsis-induced AKI: From pathogenesis to therapeutic approaches.

Sepsis is a heterogenous and highly complex clinical syndrome, which is caused by infectious or noninfectious factors. Acute kidney injury (AKI) is one of the most common and severe complication of sepsis, and it is associated with high mortality and poor outcomes. Recent evidence has identified that autophagy participates in the pathophysiology of sepsis-associated AKI. Despite the use of antibiotics, the mortality rate is still at an extremely high level in patients with sepsis. Besides traditional treatments, many natural products, including phytochemicals and their derivatives, are proved to exert protective effects through multiple mechanisms, such as regulation of autophagy, inhibition of inflammation, fibrosis, and apoptosis, etc. Accumulating evidence has also shown that many pharmacological inhibitors might have potential therapeutic effects in sepsis-induced AKI. Hence, understanding the pathophysiology of sepsis-induced AKI may help to develop novel therapeutics to attenuate the complications of sepsis and lower the mortality rate. This review updates the recent progress of underlying pathophysiological mechanisms of sepsis-associated AKI, focuses specifically on autophagy, and summarizes the potential therapeutic effects of phytochemicals and pharmacological inhibitors.

Herpes simplex virus-1 induces expression of a novel MxA isoform that enhances viral replication.

MxA is an antiviral protein induced by interferon (IFN)-α/ß that is known to inhibit the replication of many RNA viruses. In these experiments, the 76-kDa MxA protein expressed in IFN-α-treated cells was shown to have antiviral activity against herpes simplex virus-1 (HSV-1), a human DNA virus. However, MxA was expressed as a 56-kDa protein in HSV-1-infected cells in the absence of IFN-α. This previously unrecognized MxA isoform was produced from an alternatively spliced MxA transcript that had a deletion of Exons 14-16 and a frame shift altering the C-terminus. The variant MxA (varMxA) isoform was associated with HSV-1 regulatory proteins and virions in nuclear replication compartments. varMxA expression enhanced HSV-1 infection as shown by a reduction in infectious virus titers from cells in which MxA had been inhibited by RNA interference and by an increase in HSV-1 titers when the 56-kDa varMxA was expressed constitutively. Thus, the human MxA gene encodes two MxA isoforms, which are expressed differentially depending on whether the stimulus is IFN-α or HSV-1. These findings show that alternative splicing of cellular mRNA can result in expression of a novel isoform of a host defense gene that supports instead of restricting viral infection.

[Association between skin microecology and acupoint sensitization].

The skin microecology interacts with the immune system for a lifetime, and the skin microecology is in dynamic balance in the physiological state. The flora with the same physical and chemical properties on the surface of the skin can maintain a relatively stable state in a certain period of time, and there are dynamic changes of microflora in both physiology and disease state. Combined with the study of the relationship among skin microorganisms, skin diseases and visceral diseases, the relationship between skin microecological changes and visceral pathological state is explored. On this basis, it is proposed that the sensitized acupoint is an abnormal manifestation of the body homeostasis imbalance on the body surface, and the local substance variation on the sensitization acupoint may induce microbial changes. In terms of treatment, moxibustion and other surface treatments that function through immunity may also involve microorganisms.

Atorvastatin attenuates intermittent hypoxia-induced myocardial oxidative stress in a mouse obstructive sleep apnea model.

Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea (OSA), is associated with various cardiovascular diseases. In the present study, we assessed the effect of the lipid reducing agent atorvastatin on CIH-induced myocardial oxidative stress and apoptosis in a mouse OSA model. Forty-eight C57BL/6J mice were evenly divided among normoxia + vehicle, normoxia + atorvastatin, CIH + vehicle, and CIH + atorvastatin groups. CIH consisted of a hypoxia-reoxygenation cycle in which oxygen concentrations fluctuated from 21% to 6% and back over two minutes for 8 hours each day (30 events/hour). CIH exposure continued for 12 weeks. Atorvastatin (5 mg/kg) was administered from week 6 through the end of the experiment. CIH increased malondialdehyde levels and decreased superoxide dismutase activity, total antioxidant capacity, and nuclear factor erythroid 2-related factor 2 levels in cardiac tissue, indicating a reduction in antioxidant activity. Atorvastatin significantly reversed those effects (p < 0.05). CIH also increased B-cell lymphoma 2-associated protein X and cleaved caspased-3 levels as well as the myocardial apoptotic rate, as indicated by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Atorvastatin had no effect on those changes (p > 0.05). Thus, atorvastatin administration exerts antioxidant but not anti-apoptotic effects after CIH and may therefore have therapeutic potential in OSA patients with cardiovascular comorbidities.

Dependence of Photoresponsivity and On/Off Ratio on Quantum Dot Density in Quantum Dot Sensitized MoS2 Photodetector.

Non-radiative energy transfer (NRET) from quantum dots (QDs) to monolayer MoS2 has been shown to greatly enhance the photoresponsivity of the MoS2 photodetector, lifting the limitations imposed by monolayer absorption thickness. Studies were often performed on a photodetector with a channel length of only a few µm and an active area of a few µm2. Here, we demonstrate a QD sensitized monolayer MoS2 photodetector with a large channel length of 40 µm and an active area of 0.13 mm2. The QD sensitizing coating greatly enhances photoresponsivity by 14-fold at 1.3 µW illumination power, as compared with a plain monolayer MoS2 photodetector without QD coating. The photoresponsivity enhancement increases as QD coating density increases. However, QD coating also causes dark current to increase due to charge doping from QD on MoS2. At low QD density, the increase of photocurrent is much larger than the increase of dark current, resulting in a significant enhancement of the signal on/off ratio. As QD density increases, the increase of photocurrent becomes slower than the increase of dark current. As a result, photoresponsivity increases, but the on/off ratio decreases. This inverse dependence on QD density is an important factor to consider in the QD sensitized photodetector design.

[Manual acupuncture stimulation of acupoints at the same and adjacent spinal segments promotes uterine contractility].

OBJECTIVE: To investigate the effect of manual acupuncture stimulation of acupoints at different spinal nerve segments on uterine motility and the complicated adrenergic and cholinergic receptors. METHODS: Eighteen adult non-pregnant SD rats were used in the present study. The contractive activities of the uterus were measured by using a pressure transducer which was connected to an inserted water-filled balloon in the uterus via a PE tube at one end and an amplifier at the other end. Manual acupuncture needle was applied to "Zigong"(EX-CA1),"Huiyin" (CV1), "Xuehai "(SP10) and "Taichong "(LR3) acupoints located at the same or adjacent spinal nerve segments of the uterus, and to "Neiguan" (PC6) situated at the distant spinal nerve segment at about 2 Hz for 1 min, followed by observing changes of the uterine contractility. After acupuncture, α-adrenoceptor antagonist phentolamine (0.5 mg/kg, n=9) or cholinergic muscarinic (M) receptor antagonist atropine (0.5 mg/kg，n=9) was given to the rats of different acupoints respectively through tail vein, followed by observing changes of the uterine automatic systolic pressure difference (value of systolic pressure peak minuses the trough value) and frequency after manual acupuncture stimulation as well as after blocking the activities of α-adrenoceptors and M receptors, separately. RESULTS: After acupuncture stimulation of EX-CA1, CV1, SP10 and LR3, but not PC6, the systolic pressure difference and frequency of the uterus were signi-ficantly increased (P<0.05,P<0.001, P<0.01). Following intravenous injection of phentolamine, both the systolic pressure difference and frequency had no marked changes after acupuncture at the 5 acupoints (P>0.05). After intravenous injection of atropine, the uterine systolic pressure difference and frequency were markedly decreased compared with the basic values before acupuncture stimulation (P<0.001), but had no obvious changes after acupuncture at the 5 acupoints at both the same and distant spinal segments to the uterus (P>0.05). CONCLUSION: Manual acupuncture stimulation of acupoints at the same and adjacent spinal segments can promote the contractility of uterus in normal rats, which is realized by activating both α-adrenoceptor and cholinergic M receptors.

Vascular endothelial cell antigen (VECA), a novel secreted protein: overexpression in Escherichia coli of the hexahistidine- tagged protein and production of polyclonal antibodies.

A novel VECA (vascular endothelial cell antigen) was previously identified by using an antibody pool against antigens in HUVECs (human umbilical-vein endothelial cells). VECA has been evolutionarily conserved in vertebrate species ranging from frog and fish to mouse and human. Bioinformatics analysis indicated that VECA was 10.1 kDa in size, with a predicted signal sequence and transmembrane domain, indicating that VECA may have important biological functions. The present paper describes a procedure for obtaining and purifying human recombinant VECA expressed in Escherichia coli as a fusion protein, via a human VECA cDNA linked pQE30 expression vector to DNA coding for hexahistidine. The purified protein was used to raise anti-(human VECA) polyclonal antibodies, which were suitable for detecting the presence of VECA in cells, cell-culture supernatant and tissues by immunoblotting and immunohistochemistry. To our knowledge, this is the first study on the protein expression and polyclonal-antibody production for human VECA. In addition, we report for the first time the positive identification of VECA in humans at the protein and subcellular level and provide the first experimental verification that VECA was indeed a secreted protein. The anti-(human VECA) polyclonal antibodies prepared may serve as a useful tool for future biological function studies on VECA.