Efficacy and safety of culture-expanded mesenchymal stromal cell therapy in the treatment of 4 types of inflammatory arthritis: A systematic review and meta-analysis of 36 randomized controlled trials.

OBJECTIVE: This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in the treatment of inflammatory arthritis. METHODS: Two researchers conducted a comprehensive search of Chinese and English databases from their inception until July 2023. The literature screening and data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software. RESULTS: A total of 36 relevant RCTs, involving 2,076 participants, were ultimately included in this study. These RCTs encompassed four types of inflammatory arthritis, namely rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and systemic sclerosis (SSc). The results demonstrated that MSC therapy exhibited improvements in the Visual Analog Scale (VAS) for pain in OA patients (bone marrow: SMD=-0.95, 95 % CI: -1.55 to -0.36, P = 0.002; umbilical cord: SMD=-2.03, 95 % CI: -2.99 to -1.07, P < 0.0001; adipose tissue: SMD=-1.26, 95 % CI: -1.99 to -0.52, P = 0.0009). Specifically, MSCs sourced from adipose tissue showed enhancements in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (P = 0.0001), WOMAC physical function (P = 0.001), and total WOMAC scores (P = 0.0003). As for MSC therapy in RA, AS, and SSc, the current systematic review suggests a potential therapeutic effect of MSCs on these inflammatory arthritic conditions. Safety assessments indicated that MSC therapy did not increase the incidence of adverse events. CONCLUSION: MSCs have the potential to alleviate joint pain and improve joint function in patients with inflammatory arthritis. Moreover, MSC therapy appears to be relatively safe and could be considered as a viable alternative treatment option for inflammatory arthritis.

Integrating serum pharmacochemistry and network pharmacology to explore potential compounds and mechanisms of Alpiniae oxyphyllae fructus in the treatment of cellular senescence in diabetic kidney disease.

Background: Diabetic kidney disease (DKD), one of the microvascular complications in patients with diabetes mellitus, is a common cause of end-stage renal disease. Cellular senescence is believed to be an essential participant in the pathogenesis of DKD. Although there is evidence that Alpiniae oxyphyllae fructus (AOF) can ameliorate DKD progression and organismal senescence, its ability to ameliorate renal cellular senescence in DKD as well as active components and molecular mechanisms remain to be explored. Purpose: This study aimed to investigate the role of AOF in the treatment of cellular senescence in DKD and to explore its active components and potential molecular mechanisms. Methods: The pharmacological efficacy of AOF in ameliorating cellular senescence in DKD was assessed by establishing DKD mouse models and HK-2 cells under high glucose stress. UHPLC-QTOF-MS was used to screen the active compounds in AOF, which were used in conjunction with network pharmacology to predict the molecular mechanism of AOF in the treatment of cellular senescence in DKD. Results: In vivo experiments showed that AOF reduced GLU, mAlb, Scr, BUN, MDA, SOD levels, and ameliorated renal pathological damage and renal cell senescence in DKD mice. In vitro experiments showed that AOF-containing serum improved the decline in HK-2 cell viability and alleviated cellular senescence under high glucose intervention. The results of the UHPLC-QTOF-MS screened 26 active compounds of AOF. The network pharmacological analyses revealed that Cubebin, 2',6'-dihydroxy-4'-methoxydihydrochalcone, Chalcone base + 3O,1Prenyl, Batatasin IV, and Lucidenolactone were the five core compounds and TP53, SRC, STAT3, PIK3CA, and AKT1 are the five core targets of AOF in the treatment of DKD. Molecular docking simulation results showed that the five core compounds had good binding ability to the five core targets. Western blot validated the network pharmacological prediction results and showed that AOF and AOF-containing serum down-regulate the expression of TP53, and phosphorylation of SRC, STAT3, PIK3CA, and AKT. Conclusion: Our study shows that AOF may delay the development of cellular senescence in DKD by down-regulating the levels of TP53, and phosphorylation of SRC, STAT3, PIK3CA, and AKT.

High-power electrically pumped terahertz topological laser based on a surface metallic Dirac-vortex cavity.

Topological lasers (TLs) have attracted widespread attention due to their mode robustness against perturbations or defects. Among them, electrically pumped TLs have gained extensive research interest due to their advantages of compact size and easy integration. Nevertheless, limited studies on electrically pumped TLs have been reported in the terahertz (THz) and telecom wavelength ranges with relatively low output powers, causing a wide gap between practical applications. Here, we introduce a surface metallic Dirac-vortex cavity (SMDC) design to solve the difficulty of increasing power for electrically pumped TLs in the THz spectral range. Due to the strong coupling between the SMDC and the active region, robust 2D topological defect lasing modes are obtained. More importantly, enough gain and large radiative efficiency provided by the SMDC bring in the increase of the output power to a maximum peak power of 150 mW which demonstrates the practical application potential of electrically pumped TLs.

Efficacy and safety of inactivated SARS-CoV-2 vaccination in COVID-19-associated pneumonia among patients with rheumatic and musculoskeletal diseases: A real-world retrospective observational study.

OBJECTIVES: To identify the effectiveness and safety of inactivated SARS-CoV-2 vaccines in rheumatic and musculoskeletal diseases (RMDs) patients. METHODS: RMD patients with COVID-19 in Jiangsu Province were polled between December 8, 2022, and February 1, 2023. Information on demographics, disease characteristics, antirheumatic drug use, vaccination status and survival state were collected. COVID-19-associated pneumonia was the primary outcome. The effect of COVID-19 immunization on RMD patients was assessed using multivariate logistic regression, and the adverse events (AEs) following vaccination were evaluated. RESULTS: Among 592 RMD patients with COVID-19, 276 (46.6%) individuals experienced COVID-19-associated pneumonia, and 290 (49.0%) patients were injected with inactivated vaccines. In multivariate logistic regression analysis, vaccines reduced the incidence of COVID-19-associated pneumonia, and receiving booster vaccine was an independent protective factor for COVID-19-associated pneumonia in RMD patients (OR 0.64, 95% CI 0.41-0.98, p = .034). In particular, inactivated vaccines have a protective impact on RMD patients with a high risk of developing pneumonia, including those aged 45 years and older (OR 0.53, 95% CI 0.34-0.83), and who have lung involvement (OR 0.43, 95% CI 0.23-0.82). The total AEs rate of vaccines was 13.9% (40/290), only 11 (3.8%) experienced the recurrence or deterioration of RMDs, and no serious AEs occurred. CONCLUSION: Inactivated COVID-19 vaccines were safe and effective in reducing the risk of COVID-19-associated pneumonia of RMD patients in China.

Effector Cs02526 from Ciboria shiraiana induces cell death and modulates plant immunity.

Sclerotinia disease is one of the most devastating fungal diseases worldwide, as it reduces the yields of many economically important crops. Pathogen-secreted effectors play crucial roles in infection processes. However, key effectors of Ciboria shiraiana, the pathogen primarily responsible for sclerotinia disease in mulberry (Morus spp.), remain poorly understood. In this study, we identified and functionally characterized the effector Cs02526 in C. shiraiana and found that Cs02526 could induce cell deathin a variety of plants. Moreover, Cs02526-induced cell death was mediated by the central immune regulator BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1 (BAK1), dependent on a 67-amino acid fragment. Notably, Cs02526 homologues were widely distributed in hemibiotrophic and necrotrophic phytopathogenic fungi, but the homologues failed to induce cell death in plants. Pre-treatment of plants with recombinant Cs02526 protein enhanced resistance against both C. shiraiana and Sclerotinia sclerotiorum. Furthermore, the pathogenicity of C. shiraiana was diminished upon spraying plants with synthetic dsRNA-Cs02526. In conclusion, our findings highlight the cell death-inducing effector Cs02526 as a potential target for future biological control strategies against plant diseases.

Above 20†GHz high frequency operation of mid-infrared doughnut-shaped microcavity quantum cascade lasers.

Microresonator-based high-speed single-mode quantum cascade lasers are ideal candidates for on-chip optical data interconnection and high sensitivity gas sensing in the mid-infrared spectral range. In this paper, we propose a high frequency operation of single-mode doughnut-shaped microcavity quantum cascade laser at ∼4.6 µm. By leveraging compact micro-ring resonators and integrating with grounded coplanar waveguide transmission lines, we have greatly reduced the parasitics originating from both the device and wire bonding. In addition, a selective heat dissipation scheme was introduced to improve the thermal characteristics of the device by semi-insulating InP infill regrowth. The highest continuous wave operating temperature of the device reaches 288 K. A maximum -3 dB bandwidth of 11 GHz and a cut-off frequency exceeding 20 GHz in a microwave rectification technique are obtained. Benefiting from the notch at the short axis of the microcavity resonator, a highly customized far-field profile with an in-plane beam divergence angle of 2.4° is achieved.

Low-frequency regular pulse and intermittent oscillation in a mid-infrared interband cascade laser with optoelectronic feedback.

In this work, we experimentally investigate the nonlinear dynamics of a mid-infrared interband cascade laser (ICL) subject to optoelectronic feedback (OEF) through inspecting the time series and power spectrum of the laser output. The results show that, within the range of feedback strength limited by the experiment condition, the ICL sequentially presents stable state, continuously periodical oscillation (CPO), low-frequency regular pulse (LF-RP) and intermittent oscillation state with the increase of feedback strength. For the LF-RP state, the peak-to-peak value and the oscillation period increase with the increase of feedback strength. For the intermittent oscillation state, the time series is composed of the laminar region and burst region appeared alternately, and the average value and standard deviation for the duration of burst region gradually decrease with the increase of feedback strength.

3D Strain Measurement of Heterostructures Using the Scanning Transmission Electron Microscopy Moiré Depth Sectioning Method.

The mechanical properties of micro- and nanoscale materials directly determine the reliability of heterostructures, microstructures, and microdevices. Therefore, an accurate evaluation of the 3D strain field at the nanoscale is important. In this study, a scanning transmission electron microscopy (STEM) moiré depth sectioning method is proposed. By optimizing the scanning parameters of electron probes at different depths of the material, the sequence STEM moiré fringes (STEM-MFs) with a large field of view, which can be hundreds of nanometers obtained. Then, the 3D STEM moiré information constructed. To some extent, multi-scale 3D strain field measurements from nanometer to the submicrometer scale actualized. The 3D strain field near the heterostructure interface and single dislocation accurately measured by the developed method.

Stigma type and transcriptome analyses of mulberry revealed the key factors associated with Ciboria shiraiana resistance.

Ciboria shiraiana is a fungal pathogen and the causal agent of hypertrophy sorosis scleroteniosis (HSS) in mulberry, leading to substantial economic losses in the mulberry fruit-related industry. To obtain HSS resistant resources and investigate the resistance mechanism, the resistances of 14 mulberry varieties were assessed. Morus laevigata Wall. (MLW) varieties showed strong resistance to C. shiraiana, and the pathogen's infection was associated with mulberry fluorescence. Stigmas were identified as the infection site through cutting experiments. Susceptible varieties (S-varieties) displayed secretory droplets on their stigma papillar cell surfaces, while MLWs lacked these secretions. Correlation analysis between the secretion rate and the diseased fruit rate indicated that the differences between resistant varieties (R-varieties) and S-varieties were related to the stigma type. Furthermore, comparative transcriptome analysis was performed on stigma and ovary samples from R- and S-varieties. Compared with the stigma of R-varieties, the key differentially expressed genes (DEGs) with significantly higher expression in S-variety stigmas mainly participated in the fatty acid biosynthetic process. In R-variety stigmas and ovaries, the transcript levels of DEGs involved in defense response, including resistance (R) genes, were significantly higher than that of S-varieties. Overexpression of MlwRPM1-2 and MlwRGA3 enhances resistance to C. shiraiana and Sclerotinia sclerotiorum, but not Botrytis cinerea in tobacco. These findings help us explain the different resistance mechanisms of mulberry to C. shiraiana, and the critical defense genes in R-varieties can be applied to breeding antifungal plant varieties.

Inserting self-assembled InAs quantum dots into quantum cascade lasers to achieve a broadband free-running frequency comb and effective radio-frequency injection.

We present what we belive to be a new band design in which self-assembled InAs quantum dots (QD) are embedded in InGaAs quantum wells (QW) to fabricate broadband single-core quantum dot cascade lasers (QDCLs) operating as frequency combs. The hybrid active region scheme was exploited to form upper hybrid QW/QD energy states and lower pure QD energy states, which expanded the total laser bandwidth by up to 55 cm-1 due to a broad gain medium provided by the inherent spectral inhomogeneity of self-assembled QDs. The continuous-wave (CW) output power of these devices was as high as 470 mW with optical spectra centered at ∼7 µm, which allowed CW operation at temperatures up to 45 °C . Remarkably, measurement of the intermode beatnote map revealed a clear frequency comb regime extending over a continuous 200 mA current range. Moreover, the modes were self-stabilized with intermode beatnote linewidths of approximately 1.6 kHz. Furthermore, what we believe to be a novel π-shaped electrode design and coplanar waveguide transition way were used for RF signal injection. We found that RF injection modified the laser spectral bandwidth by up to 62 cm-1. The developing characteristics indicate the potential for comb operation based on QDCLs as well as the realization of ultrafast mid-infrared pulse.

Near-Full Current Dynamic Range THz Quantum Cascade Laser Frequency Comb.

The present study proposes a terahertz quantum cascade laser frequency comb (THz QCL FC) with a semi-insulated surface plasma waveguide characterized by a low threshold current density, high power and a wide current dynamic range. The gain dispersion value and the nonlinear susceptibility were optimized based on the combination of a hybrid bound-to-continuum active region with a semi-insulated surface plasmon waveguide. Without any extra dispersion compensator, stable frequency comb operation within a current dynamic range of more than 97% of the total was revealed by the intermode beat note map. Additionally, a total comb spectral emission of about 300 GHz centered around 4.6 THz was achieved for a 3 mm long and 150 µm wide device. At 10 K, a maximum output power of 22 mW was obtained with an ultra-low threshold current density of 64.4 A·cm-2.

Continuous-wave microcavity quantum cascade lasers in whispering-gallery modes up to 50 °C.

Micro-resonator-based lasers are well suited for high-density optoelectronic integration because of their small volumes and low thresholds. However, microcavity quantum cascade lasers for on-chip sensing have high thermal loads that make continuous-wave operation challenging. In this work, we designed an selective thermal dissipation scheme for the selective electrical isolation process to improve the thermal conductivity of the devices. The lasers operated at 50 °C, with 4.7-µm emission. They were fabricated as a notched elliptical resonator, resulting in a highly unidirectional far-field profile with an in-plane beam divergence of 1.9°. Overall, these directional-emission quantum cascade lasers pave the way for portable and highly integrated sensing applications.

Psychological stress in inflammatory bowel disease: Psychoneuroimmunological insights into bidirectional gut-brain communications.

Inflammatory bowel disease (IBD), mainly including ulcerative colitis (UC) and Crohn's disease (CD), is an autoimmune gastrointestinal disease characterized by chronic inflammation and frequent recurrence. Accumulating evidence has confirmed that chronic psychological stress is considered to trigger IBD deterioration and relapse. Moreover, studies have demonstrated that patients with IBD have a higher risk of developing symptoms of anxiety and depression than healthy individuals. However, the underlying mechanism of the link between psychological stress and IBD remains poorly understood. This review used a psychoneuroimmunology perspective to assess possible neuro-visceral integration, immune modulation, and crucial intestinal microbiome changes in IBD. Furthermore, the bidirectionality of the brain-gut axis was emphasized in the context, indicating that IBD pathophysiology increases the inflammatory response in the central nervous system and further contributes to anxiety- and depression-like behavioral comorbidities. This information will help accurately characterize the link between psychological stress and IBD disease activity. Additionally, the clinical application of functional brain imaging, microbiota-targeted treatment, psychotherapy and antidepressants should be considered during the treatment and diagnosis of IBD with behavioral comorbidities. This review elucidates the significance of more high-quality research combined with large clinical sample sizes and multiple diagnostic methods and psychotherapy, which may help to achieve personalized therapeutic strategies for IBD patients based on stress relief.

High-performance quantum cascade lasers at λ ∼ 9†µm grown by MOCVD.

We demonstrate a high power InP-based quantum cascade laser (QCL) (λ ∼ 9 µm) with high characteristic temperature grown by metalorganic chemical vapor deposition (MOCVD) in this article. A 4-mm-long cavity length, 10.5-µm-wide ridge QCL with high-reflection (HR) coating demonstrates a maximum pulsed peak power of 1.55 W and continuous-wave (CW) output power of 1.02W at 293 K. The pulsed threshold current density of the device is as low as 1.52 kA/cm2. The active region adopted a dual-upper-state (DAU) and multiple-lower-state (MS) design and it shows a wide electroluminescence (EL) spectrum with 466 cm-1 wide full-width at half maximum (FWHM). In addition, the device performance is insensitive to the temperature change since the threshold-current characteristic temperature coefficient, T0, is as high as 228 K, and slope-efficiency characteristic temperature coefficient, T1, is as high as 680 K, over the heatsink-temperature range of 293 K to 353 K.

Phase-locked terahertz quantum cascade laser array integrated with a Talbot cavity.

Increasing the power of a quantum cascade laser by widening laser ridges will lead to the degradation of the beam quality because of the operation of high-order transverse modes. We report on a phase-locked array scheme of terahertz quantum cascade laser (THz QCL) utilizing Talbot effect. By adjusting the absorbing boundary width of each ridge in the array, stable operation of the fundamental supermode is realized. A five-element array shows 4 times power amplification than that of a single ridge device. Due to the large power amplification efficiency, stable mode selection, and simple fabricating process, the phase-locked array scheme is very promising to further improve the performance of THz QCL.

Monolithically integrated mid-infrared sensor with a millimeter-scale sensing range.

On-chip sensors based on quantum cascade laser technology are attracting broad attention because of their extreme compactness and abundant absorption fingerprints in the mid-infrared wavelength range. Recent continuous wave operation microcavity quantum cascade lasers are well suited for high-density optoelectronic integration because their volumes are small and thresholds are low. In this experimental work, we demonstrate a monolithically integrated sensor comprising a notched elliptical resonator as transmitter, a quantum cascade detector as receiver, and a surface plasmon structure as light-sensing waveguide. The sensor structure is designed to exploit the highly unidirectional lasing properties of the notched elliptical resonator to increase the optical absorption path length. Combined with the evanescent nature of the dielectric loaded surface plasmon polariton waveguides, the structure also ensures a strong light-matter interactions. The sensing transmission distance obtained is approximately 1.16 mm, which is about one order of magnitude improvement over the traditional Fabry-Perot waveguide. This sensor opens new opportunities for long-range and high-sensitivity on-chip gas sensing and spectroscopy.

Broad tuning range, high power quantum cascade laser at λ ∼ 7.4 µm.

In this article, we report a high power quantum cascade laser (QCL) at λ∼7.4 µm with a broad tuning range. By carefully designing and optimizing the active region and waveguide structure, a continuous-wave (CW) output power up to 1.36 W and 0.5 W is achieved at 293 K and 373 K which shows the excellent temperature stability. A high wall-plug efficiency (WPE) of 8% and 13.6% in CW and pulsed mode at 293 K are demonstrated. The laser shows a characteristic temperature T0 of 224 K and T1 of 381 K over a temperature range from 283 K to 373 K. In addition, a far field of pure zero order transverse mode and a fairly wide external cavity (EC) tuning range (280 cm-1) from 6.54 µm to 8 µm are achieved in pulsed operation. In addition, an EC single mode output power of 226 mW is obtained under CW operation at 293K.

GaSb surface grating distributed feedback interband cascade laser emitting at 3.25 µm.

A second-order distributed feedback interband cascade laser emitting at 3.25 µm was designed, grown, and fabricated. By coherent epitaxy of a GaSb cap layer instead of the conventional thin InAs cap on top of the laser structure, a high-quality surface grating was made of GaSb and gold. Enough coupling strength and a significant inter-modal loss difference were predicted according to the simulation within the framework of couple-wave theory. Lasers having 2-mm-long cavities and 4.5-µm-wide ridges with high-/anti-reflection coatings were fabricated. The continuous-wave threshold current and maximum single-mode output power were 60 mA and 24 mW at 20°C, respectively. The output power of 5 mW was still kept at 55°C. Continuous tuning free from mode hopping and high single-mode suppression ratios (>20 dB) were realized at all injection currents and heat-sink temperatures, covering a spectral range of over 20 cm-1.

Chromosome-level Genomes Reveal the Genetic Basis of Descending Dysploidy and Sex Determination in Morus Plants.

Multiple plant lineages have independently evolved sex chromosomes and variable karyotypes to maintain their sessile lifestyles through constant biological innovation. Morus notabilis, a dioecious mulberry species, has the fewest chromosomes among Morus spp., but the genetic basis of sex determination and karyotype evolution in this species has not been identified. In this study, three high-quality genome assemblies were generated for Morus spp. [including dioecious M. notabilis (male and female) and Morus yunnanensis (female)] with genome sizes of 301-329 Mb and were grouped into six pseudochromosomes. Using a combination of genomic approaches, we found that the putative ancestral karyotype of Morus species was close to 14 protochromosomes, and that several chromosome fusion events resulted in descending dysploidy (2n = 2x = 12). We also characterized a ∼ 6.2-Mb sex-determining region on chromosome 3. Four potential male-specific genes, a partially duplicatedDNA helicase gene (named MSDH) and three Ty3_Gypsy long terminal repeat retrotransposons (named MSTG1/2/3), were identified in the Y-linked area and considered to be strong candidate genes for sex determination or differentiation. Population genomic analysis showed that Guangdong accessions in China were genetically similar to Japanese accessions of mulberry. In addition, genomic areas containing selective sweeps that distinguish domesticated mulberry from wild populations in terms of flowering and disease resistance were identified. Our study provides an important genetic resource for sex identification research and molecular breeding in mulberry.