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Myelodysplastic syndromes (MDS) are a rare form of early-stage blood cancer that typically leads to leukemia and other deadly complications. The typical diagnosis for MDS involves a mixture of blood tests, a bone marrow biopsy, and genetic analysis. Flow cytometry has commonly been used to analyze these types of samples, yet there still seems to be room for advancement in several areas, such as the limit of detection, turnaround time, and cost. This paper explores recent advancements in microflow cytometry technology and how it may be used to supplement conventional methods of diagnosing blood cancers, such as MDS and leukemia, through flow cytometry. Microflow cytometry, a more recent adaptation of the well-researched and conventional flow cytometry techniques, integrated with microfluidics, demonstrates significant potential in addressing many of the shortcomings flow cytometry faces when diagnosing a blood-related disease such as MDS. The benefits that this platform brings, such as portability, processing speed, and operating cost, exemplify the importance of exploring microflow cytometry as a point-of-care (POC) diagnostic device for MDS and other forms of blood cancer.

In this paper, we report a new model for passively Q-switched intracavity optical parametric oscillators (IC-OPOs), using Cr:YAG as a Q-switch crystal. The model considers the effects of thermalization in the Nd:YAG laser crystal, excited state absorption in the Cr:YAG saturable absorber, nonlinear loss due to pump depletion in the nonlinear crystal, the thermal lens effect and the mode overlap of the fields within the nonlinear crystal. The calculated pulse width for the 1,064 nm pump light was 6.2 ns compared to the experimental result of 6 ns, while the signal wave was calculated to have a pulse width of 1.75 ns compared to the experimental result of 2 ns. The model is shown to accurately calculate both the temporal and output power characteristics of the IC-OPO, which has not been previously reported to the best of our knowledge.

In this paper, we report a theoretical systematic study of continuous wave intracavity backwards optical parametric oscillators based on periodically poled lithium niobate (PPLN) for mid-infrared (mid-IR) light generation. We study the effects of varying different cavity parameters including nonlinear crystal length, cavity size, pump laser diode spot size, output coupler radius, and cavity loss values on the output power and threshold of the proposed mid-IR laser. The effects of different physical phenomena are included in the model including pump depletion due to the nonlinear conversion process, the thermal lens effect, and mode overlap between the beams in the nonlinear crystal. We show that high output powers in the mid infrared (>500 mW at 3.2 μm) can be achieved with proper cavity design and that a laser threshold with a PPLN as short as 2 cm can be reached.

We report a diode-pumped solid-state (DPSS) laser used for intracavity pump-enhanced difference frequency generation (DFG) to create a 3.5-micron laser. Using a 50 mm-long periodically poled lithium niobate (PPLN) crystal inside the cavity of an Nd:YVO4 solid-state laser at 1064 nm with 4.5 W pump power at 808 nm, and a 310 mW C-band signal at 1529 nm, up to 31 mW of mid-infrared output power at 3499 nm is obtained. The cavity requires no active stabilization and/or locking, and the entire cavity is −1, which is the highest value reported to date for continuous-wave DFG based on a bulk nonlinear optical crystal with no active stabilization. Potential future applications in free-space optical communication are also discussed.

The global economic and healthcare crises experienced over the past three years, as a result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has significantly impacted the commonplace habits of humans around the world. SARS-CoV-2, the virus responsible for the coronavirus 2019 (COVID-19) phenomenon, has contributed to the deaths of millions of people around the world. The potential diagnostic applications of microfluidic devices have previously been demonstrated to effectively detect and quasi-quantify several different well-known viruses such as human immunodeficiency virus (HIV), influenza, and SARS-CoV-2. As a result, microfluidics has been further explored as a potential alternative to our currently available rapid tests for highly virulent diseases to better combat and manage future potential outbreaks. The outbreak management during COVID-19 was initially hindered, in part, by the lack of available quantitative rapid tests capable of confirming a person’s active infectiousness status. Therefore, this review will explore the use of microfluidic technology, and more specifically RNA-based virus detection methods, as an integral part of improved diagnostic capabilities and will present methods for carrying the lessons learned from COVID-19 forward, toward improved diagnostic outcomes for future pandemic-level threats. This review will first explore the context of the COVID-19 pandemic and how diagnostic technology was shown to have required even greater advancements to keep pace with the transmission of such a highly infectious virus. Secondly, the historical significance of integrating microfluidic technology in diagnostics and how the different types of genetic-based detection methods may vary in their potential practical applications. Lastly, the review will summarize the past, present, and future potential of RNA-based virus detection/diagnosis and how it might be used to better prepare for a future pandemic.

Abstract In this paper, a systematic study of the relationship between nonlinear crystal length and intracavity second-harmonic generation (SHG) using MgO-doped periodically-poled lithium niobate (MgO:PPLN) is presented. The experimental results demonstrate a relationship between the maximum SHG power generated and the full-width at half maximum (FWHM) of the crystal’s temperature tuning curve to the length of the nonlinear optical crystal. It was shown that maximum SHG power increases rapidly with the increase of MgO:PPLN length, reaching a saturation length (~ 2 mm), which is much shorter than that predicted by the single-pass SHG theory. This saturation length of the MgO:PPLN crystal is almost independent on 808 nm pump power for typical powers used in continuous wave intracavity SHG lasers. In addition to this saturation effect, a broadening effect was also observed, the FWHM of the temperature tuning curve was shown to have a larger FWHM than that predicted by the single-pass SHG theory for MgO:PPLN shorter than the saturation length. This work has the benefit of allowing engineers to optimize nonlinear crystal length when developing intracavity SHG based diode-pumped solid state (DPSS) lasers.

Acupuncture is one of the most extensively used complementary and alternative medicine therapies worldwide. In this study, we explore the use of near-infrared light-emitting diodes (LEDs) to provide acupuncture-like physical stimulus to the skin tissue, but in a completely non-invasive way. A computational modeling framework has been developed to investigate the light-tissue interaction within a three-dimensional multi-layer model of skin tissue. Finite element-based analysis has been conducted, to obtain the spatiotemporal temperature distribution within the skin tissue, by solving Pennes’ bioheat transfer equation, coupled with the Beer-Lambert law. The irradiation profile of the LED has been experimentally characterized and imposed in the numerical model. The experimental validation of the developed model has been conducted through comparing the numerical model predictions with those obtained experimentally on the agar phantom. The effects of the LED power, treatment duration, LED distance from the skin surface, and usage of multiple LEDs on the temperature distribution attained within the skin tissue have been systematically investigated, highlighting the safe operating power of the selected LEDs. The presented information about the spatiotemporal temperature distribution, and critical factors affecting it, would assist in better optimizing the desired thermal dosage, thereby enabling a safe and effective LED-based photothermal therapy.

Sexual generation is an important generation in the life cycle of host-alternating aphids, and its population size determines the intensity of the peak in the next spring. Although male trapping techniques based on olfactory stimuli have been successfully established in the field, the biological basis of olfactory perception in males is unclear. In this study, we compared the morphology of antennae and the types, sizes, numbers, and distribution of sensilla between males and sexual females in the host-alternating aphid Semiaphis heraclei (Hemiptera: Aphididae). We found that flagellum length differentiation contributed to the majority of the sexual dimorphism of antennae. Most sensillum types or subtypes, including trichoid sensilla subtype I, campaniform sensilla, and primary rhinaria subtypes I and II, were enlarged in males. In addition, males bore more trichoid sensilla subtype I than sexual females. In particular, secondary rhinaria were present in males only and could not be detected in sexual females. These results revealed the structural basis of male olfactory perception. Our findings provide insight into the mechanism underlying chemical communication between sexual aphids and could thus be useful for pest control.

The eutrophication of aquatic ecosystems caused by rapid human urbanization has led to an increased production of potentially hazardous bacterial populations, known as blooms. One of the most notorious forms of these aquatic blooms are cyanobacteria, which in sufficiently large quantities can pose a hazard to human health through ingestion or prolonged exposure. Currently, one of the greatest difficulties in regulating and monitoring these potential hazards is the early detection of cyanobacterial blooms, in real time. Therefore, this paper presents an integrated microflow cytometry platform for label-free phycocyanin fluorescence detection, which can be used for the rapid quantification of low-level cyanobacteria and provide early warning alerts for potential harmful cyanobacterial blooms. An automated cyanobacterial concentration and recovery system (ACCRS) was developed and optimized to reduce the assay volume, from 1000 mL to 1 mL, to act as a pre-concentrator and subsequently enhance the detection limit. The microflow cytometry platform utilizes an on-chip laser-facilitated detection to measure the in vivo fluorescence emitted from each individual cyanobacterial cell, as opposed to measuring overall fluorescence of the whole sample, potentially decreasing the detection limit. By applying transit time and amplitude thresholds, the proposed cyanobacteria detection method was verified by the traditional cell counting technique using a hemocytometer with an R2 value of 0.993. It was shown that the limit of quantification of this microflow cytometry platform can be as low as 5 cells/mL for Microcystis aeruginosa, 400-fold lower than the Alert Level 1 (2000 cells/mL) set by the World Health Organization (WHO). Furthermore, the decreased detection limit may facilitate the future characterization of cyanobacterial bloom formation to better provide authorities with ample time to take the appropriate actions to mitigate human risk from these potentially hazardous blooms.

The rapid detection and quantification of infectious pathogens is an essential component to the control of potentially lethal outbreaks among human populations worldwide. Several of these highly infectious pathogens, such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been cemented in human history as causing epidemics or pandemics due to their lethality and contagiousness. SARS-CoV-2 is an example of these highly infectious pathogens that have recently become one of the leading causes of globally reported deaths, creating one of the worst economic downturns and health crises in the last century. As a result, the necessity for highly accurate and increasingly rapid on-site diagnostic platforms for highly infectious pathogens, such as SARS-CoV-2, has grown dramatically over the last two years. Current conventional non-microfluidic diagnostic techniques have limitations in their effectiveness as on-site devices due to their large turnaround times, operational costs and the need for laboratory equipment. In this review, we first present criteria, both novel and previously determined, as a foundation for the development of effective and viable on-site microfluidic diagnostic platforms for several notable pathogens, including SARS-CoV-2. This list of criteria includes standards that were set out by the WHO, as well as our own “seven pillars” for effective microfluidic integration. We then evaluate the use of microfluidic integration to improve upon currently, and previously, existing platforms for the detection of infectious pathogens. Finally, we discuss a stage-wise means to translate our findings into a fundamental framework towards the development of more effective on-site SARS-CoV-2 microfluidic-integrated platforms that may facilitate future pandemic diagnostic and research endeavors. Through microfluidic integration, many limitations in currently existing infectious pathogen diagnostic platforms can be eliminated or improved upon.

A rapid, sensitive and simple microflow cytometry-based agglutination immunoassay (MCIA) was developed for point-of-care (POC) quantitative detection of SARS-CoV-2 IgM and IgG antibodies. The antibody concentration was determined by using the transit time of beads aggregates. A linear relationship was established between the average transit time and the concentration of SARS-CoV-2 IgM and IgG, respectively. The limit of detection (LOD) of SARS-CoV-2 IgM and IgG by the MCIA measurement are 0.06 mg/L and 0.10 mg/L, respectively. The 10 µL sample consumption, 30 min assay time and the compact setup make this technique suitable for POC quantitative detection of SARS-CoV-2 antibodies.

An accurate and rapid microflow cytometry-based agglutination immunoassay (MCIA) suitable for on-site antibody or antigen detection was proposed. In this study, quantitative C-reactive protein (CRP) detection was chosen as a model assay in order to demonstrate the detection principle. The average transit time was employed to estimate the extent of the agglutination reaction and improve the detection accuracy as compared to the intensity-dependent methods. The detection time was less than 8 min. and only a 20 µL serum sample was needed for each test. The results showed a linear relationship between the average transit time of aggregates and CRP concentrations ranging from 0 to 1 µg/mL. The R2 of this relationship was 0.99. The detection limit of this technology was 0.12 µg/mL CRP. The system used for CRP detection can be extended to also monitor other clinically relevant molecules.

Background/Aims: In the present study, we describe a novel and straightforward approach to produce a cyclic- arginine-glycine-aspartic (RGD)-peptide-conjugated quantum dot (QD) probe as an ideal target tumor biomarker. Due to its specific structure, the probe can be used for targeted imaging of pancreatic carcinoma cells. Methods: Pancreatic carcinoma cells were routinely cultured and marked with QD-RGD probe. The QD-RGD probe on the fluorescence-labeled cancer cell was observed by fluorescence microscopy and laser confocal microscopy. Cancer cell viability was detected by MTT assay after culturing with QD-RGD probe. Results: Fluorescence microscopy and laser confocal microscopy displayed that 10nmol/L QD-RGD probe was able to effectively mark pancreatic carcinoma cells. In comparison with organic dyes and fluorescent proteins, the quantum dot-RGD probe had unique optical and electronic properties. Conclusion: QD-RGD probe has a low cytotoxicity with an excellent optical property and biocompatibility. These findings support further evaluation of QD-RGD probes for the early detection of pancreatic cancer.

Background: Propofol and etomidate are the most important intravenous general anesthetics in the current clinical use and that mediate gamma-aminobutyric acid's (GABAergic) synaptic transmission. However, their long-term effects on GABAergic synaptic transmission induced by neonatal propofol or etomidate exposure remain unclear. We investigated the long-term GABAergic neurotransmission alterations, following neonatal propofol and etomidate administration. Methods: Sprague-Dawley rat pups at postnatal days 4–6 were underwent 6-h-long propofol-induced or 5-h-long etomidate-induced anesthesia. We performed whole-cell patch-clamp recording from pyramidal cells in the cornus ammonis 1 area of acute hippocampal slices of postnatal 80–90 days. Spontaneous and miniature inhibitory GABAergic currents (spontaneous inhibitory postsynaptic currents [sIPSCs] and miniature inhibitory postsynaptic currents [mIPSCs]) and their kinetic characters were measured. The glutamatergic tonic effect on inhibitory transmission and the effect of bumetanide on neonatal propofol exposure were also examined. Results: Neonatal propofol exposure significantly increased the frequency of mIPSCs (from 1.87 ± 0.35 Hz to 3.43 ± 0.51 Hz, P< 0.05) and did not affect the amplitude of mIPSCs and sIPSCs. Both propofol and etomidate slowed the decay time of mIPSCs kinetics (168.39 ± 27.91 ms and 267.02 ± 100.08 ms vs. 68.18 ± 12.43 ms; P< 0.05). Bumetanide significantly blocked the frequency increase and reversed the kinetic alteration of mIPSCs induced by neonatal propofol exposure (3.01 ± 0.45 Hz and 94.30 ± 32.56 ms). Conclusions: Neonatal propofol and etomidate exposure has long-term effects on inhibitory GABAergic transmission. Propofol might act at pre- and post-synaptic GABA receptor A (GABAA) receptors within GABAergic synapses and impairs the glutamatergic tonic input to GABAergic synapses; etomidate might act at the postsynaptic site.

Aims: Calcium-sensing receptor (CaR) acts as a G protein coupled receptor that mediates the increase of the intracellular Ca2+ concentration. The expression of CaR has been confirmed in various cell types, including cardiomyocytes, smooth muscle cells, neurons and vascular endothelial cells. However, whether CaR is expressed and functions in cardiac fibroblasts has remained unknown. The present study investigated whether CaR played a role in cardiac fibroblast proliferation and extracellular matrix (ECM) secretion, both in cultured rat neonatal cardiac fibroblasts and in a model of cardiac hypertrophy induced by isoproterenol (ISO). Methods and Results: Immunofluorescence, immunohistochemistry and Western blot analysis revealed the presence of CaR in cardiac fibroblasts. Calcium and calindol, a specific activator of CaR, elevated the intracellular calcium concentration in cardiac fibroblasts. Pretreatment of cardiac fibroblasts with calhex231, a specific inhibitor of CaR, U73122 and 2-APB attenuated the calindol- and extracellular calcium-induced increase in intracellular calcium ([Ca2+]i). Cardiac fibroblast proliferation and migration were assessed by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), cell count and the cell scratch assay. ECM production was detected by expression of matrix metalloproteinase-3 and -9 (MMP-3 and -9). Activation of CaR promoted cardiac fibroblast proliferation and migration and ECM secretion. More importantly, calhex231, suppressed cardiac fibroblast proliferation and migration and MMP-3 and -9 expression. To further investigate the effect of CaR on cardiac fibrosis, a model of ISO-induced cardiac hypertrophy was established. Pretreatment with calhex231 prevented cardiac fibrosis and decreased the expression of MMP-3 and -9 expression. Conclusions: Our results are the first report that CaR plays an important role in Ca2+ signaling involved in cardiac fibrosis through the phospholipase C- inositol 3,4,5 phosphate (PLC-IP3) pathway.

In this paper, diode pumped solid state (DPSS) lasers based on end-pumping series Nd:YVO4 and Nd:GdVO4 crystals were studied. Dual-, tri-, and quad-wavelength emissions were achieved. In the dual-wavelength emission operation, an optical-to-optical efficiency (O-O) of 47% and the power instability was 0.6% were obtained. These are the most efficient and compact lasers operating in continuous wave mode reported to date with series crystals. Besides this, the effect of changing power ratio between the output laser powers on speckle reduction was investigated for the first time. In addition, tri and quad wavelength emissions were achieved with a reasonable efficiency simply by optimizing the cavity parameters.

Aims: Alterations in calcium homeostasis in the intracellular endo/sarcoplasmic reticulum (ER/SR) and mitochondria of cardiomyocytes cause cell death via the SR and mitochondrial apoptotic pathway, contributing to ventricular dysfunction. However, the role of the calcium-sensing receptor (CaR) in cardiac hypertrophy and heart failure has not been studied. This study examined the possible involvement of CaR in the SR and mitochondrial apoptotic pathway in an experimental model of heart failure. Methods and Results: In Wistar rats, cardiac hypertrophy and heart failure were induced by subcutaneous injection of isoproterenol (Iso). Calindol, an activator of CaR, and calhex231, an inhibitor of CaR, were administered by caudal vein injection. Cardiac remodeling and left ventricular function were then analyzed in these rats. After 2, 4, 6 and 8 weeks after the administration of Iso, the rats developed cardiac hypertrophy and failure. The cardiac expression of ER chaperones and related apoptotic proteins was significantly increased in the failing hearts. Furthermore, the expression of ER chaperones and the apoptotic rate were also increased with the administration of calindol, whereas the expression of these proteins was reduced with the treatment of calhex231. We also induced cardiac hypertrophy and failure via thoracic aorta constriction (TAC) in mice. After 2 and 4 weeks of TAC, the expression of ER chaperones and apoptotic proteins were increased in the mouse hearts. Furthermore, Iso induced ER stress and apoptosis in cultured cardiomyocytes, while pretreatment with calhex231 prevented ER stress and protected the myocytes against apoptosis. To further investigate the effect of CaR on the concentration of intracellular calcium, the calcium concentration in the SR and mitochondria was determined with Fluo-5N and x-rhod-1 and the mitochondrial membrane potential was examined with JC-1 using laser confocal microscopy. After treatment with Iso for 48 hours, activation of CaR reduced [Ca2+]SR, increased [Ca2+]m, decreased the mitochondrial membrane potential, increased the expression of ER stress chaperones and related apoptotic proteins, and induced the release of cytochrome c from the mitochondria. Conclusions: Our results demonstrated that CaR activation caused Ca2+ release from the SR into the mitochondria and induced cardiomyocyte apoptosis through the SR and mitochondrial apoptotic pathway in failing hearts.

Fabrication and performance of a functional photonic-microfluidic flow cytometer is demonstrated. The devices are fabricated on a Pyrex substrate by photolithographically patterning the microchannels and optics in a SU-8 layer that is sealed via a poly(dimethylsiloxane) (PDMS) layer through a unique chemical bonding method. The resulting devices eliminate the free-space excitation optics through integration of microlenses onto the chip to mimic conventional cytometry excitation. Devices with beam waists of 6 μm and 12 μm in fluorescent detection and counting tests using 2.5 and 6 μm beads-show CVs of 9%–13% and 23% for the two devices, respectively. These results are within the expectations for a conventional cytometer (5%–15%) and demonstrate the ability to integrate the photonic components for excitation onto the chip and the ability to maintain the level of reliable detection.

Abstract In this paper, we give sufficient conditions or realizability criteria for the existence of a row stochastic matrix with a given spectrum Λ = {λ1, ..., λn} = Λ1 ∪ ⋯ ∪ Λm ∪ Λm+1, m > 0; where (pk is an integer greater than 1), λk1 = λk > 0, 1 = λ1 ≥ ωk > 0, k = 1, ..., m; Λm+1 = {λm+1}, ωm+1 ≡ λ1 + ..., +λn ≤ λ1, ωk ≥ λk, ω1 ≥ λk, k = 2, ..., m + 1. In the case when p1, ..., pm are all equal to 2, Λ becomes a list of 2m + 1 real numbers for any positive integer m, and our result gives sufficient conditions for a list of 2m + 1 real numbers to be realizable by a row stochastic matrix. AMS classification: 15A18.

In the previous paper by the first and the third authors, we present six algorithms for determining whether a given symmetric matrix is strictly copositive, copositive (but not strictly), or not copositive. The algorithms for matrices of order are not guaranteed to produce an answer. It also shows that for 1000 symmetric random matrices of order 8, 9, and 10 with unit diagonal and with positive entries all being less than or equal to 1 and negative entries all being greater than or equal to , there are 8, 6, and 2 matrices remaing undetermined, respectively. In this paper we give two more algorithms for and our experiment shows that no such matrix of order 8 or 9 remains undetermined; and almost always no such matrix of order 10 remains undetermined. We also do some discussion based on our experimental results.

Objective: To evaluate the clinical efficacy and immune function of Daratumumab combined with chemotherapy in patients with relapsed/refractory multiple myeloma (RRMM). Methods: Eighty patients with RRMM treated in Xingtai People’s Hospital from January, 2020 to December, 2021 were randomly divided into two groups. Patients in the study group were treated with Daratumumab combined with PAD regimen, while patients in the control group were provided with PAD regimen alone. Further comparison was performed on the therapeutic effects, adverse drug reactions, the levels of T lymphocyte subsets CD3+, CD4+, CD8+ and CD4+ /CD8+, the positive expression rate of CD38 and the expression level of Notch-1 on the membrane of plasma cells between the two groups. Results: The overall response rate in the study group (67.50%) was significantly better than that in the control group (45.00%). There was no significant difference in the incidence of adverse reactions between the two groups. After treatment, the reviewed levels of CD3+, CD4+ and CD4+ /CD8+ were obviously higher in the study group than those in the control group, while the positive expression rate of CD38 and the expression level of Notch one on the membrane of plasma cells were both lower than those in the control group (p<0.05). Conclusion: Daratumumab combined with a PAD regimen is a safe and effective approach that has a definite curative effect on patients with RRMM, which can improve immune function significantly and result in no significant increase in adverse reactions. [ABSTRACT FROM AUTHOR]