Incomplete filling in the basal region of maize endosperm: timing of development of starch synthesis and cell vitality.

Starch synthesis in maize endosperm adheres to the basipetal sequence from the apex downwards. However, the mechanism underlying nonuniformity among regions of the endosperm in starch accumulation and its significance is poorly understood. Here, we examined the spatiotemporal transcriptomes and starch accumulation dynamics in apical (AE), middle (ME), and basal (BE) regions of endosperm throughout the filling stage. Results demonstrated that the BE had lower levels of gene transcripts and enzymes facilitating starch synthesis, corresponding to incomplete starch storage at maturity, compared with AE and ME. Contrarily, the BE showed abundant gene expression for genetic processing and slow progress in physiological development (quantified by an index calculated from the expression values of development progress marker genes), revealing a sustained cell vitality of the BE. Further analysis demonstrated a significant parabolic correlation between starch synthesis and physiological development. An in-depth examination showed that the BE had more active signaling pathways of IAA and ABA than the AE throughout the filling stage, while ethylene showed the opposite pattern. Besides, SNF1-related protein kinase1 (SnRK1) activity, a regulator for starch synthesis modulated by trehalose-6-phosphate (T6P) signaling, was kept at a lower level in the BE than the AE and ME, corresponding to the distinct gene expression in the T6P pathway in starch synthesis regulation. Collectively, the findings support an improved understanding of the timing of starch synthesis and cell vitality in regions of the endosperm during development, and potential regulation from hormone signaling and T6P/SnRK1 signaling.

Improving Buried Interface Contact by Bidentate Anchoring for Inverted Perovskite Solar Cells.

Nickel oxide (NiOx) is a promising hole transport layer (HTL) to fabricate efficient and large-scale inverted perovskite solar cells (PSCs) due to its low cost and superior chemical stability. However, inverted PSCs based on NiOx are still lagging behind that of other HTL because of the poor quality of buried interface contact. Herein, a bidentate ligand, 4,6-bis (diphenylphosphino) phenoxazine (2DPP), is used to regulate the NiOx surface and perovskite buried interface. The diphosphine Lewis base in the 2DPP molecule can coordinate both with NiOx and lead ions at NiOx/perovskite interface, leading to high-quality perovskite films with minimized defects. It is found that the inverted PSCs with 2DPP-modified buried interface exhibit double advantages of being both fast charge extraction and reduced nonradiative recombination, which is a combination of multiple factors including favorable energetic alignment, improved interface contact and strong binding between NiOx/2DPP and perovskite. The optimal PSC based on 2DPP modification yields a champion power conversion efficiency (PCE) of 21.9%. The unencapsulated PSC maintains above 75% of its initial PCE in the air with a relative humidity (RH) of 30-40% for 1000 h.

Investigation on screening, identification, and fermentation characteristics of Yunnan olive in the fermented liquid utilizing five strains of Saccharomyces cerevisiae.

Refined indigenous Saccharomyces cerevisiae can enhance refinement, sophistication, and subtlety of fruit wines by showcasing exceptional regional characteristics. In order to identify exceptional indigenous S. cerevisiae strains from Yunnan olive, this study isolated 60 yeast strains from wild Yunnan olive fermentation mash. The five S. cerevisiae strains were subjected to morphological and molecular biological identification, followed by evaluation of their fermentation performance, ethanol production capacity, ester production capacity, H2S production capacity, killing capacity, and tolerance. Strains LJM-4, LJM-10, and LJM-26 exhibited robust tolerance to 6% ethanol volume fraction, pH 2.8, sucrose concentration of 400 g/L, SO2 concentration of 0.3 g/L, glucose concentration of 400 g/L at both 40 °C and 15 °C. Additionally, strain LJM-10 demonstrated a faster fermentation rate compared to the other strains. Among the tested S. cerevisiae strains evaluated in this study for olive wine fermentation process in Yunnan region; strain LJM-10 displayed superior abilities in terms of ester and ethanol production while exhibiting the lowest H2S production levels. These findings suggest that strain LJM-10 holds great potential as an excellent candidate for optimizing fruit wine S. cerevisiae fermentation processes in Yunnan olive fruit wine.

Isolation, identification, and tolerance analysis of yeast during the natural fermentation process of Sidamo coffee beans.

Yeast, which plays a pivotal role in the brewing, food, and medical industries, exhibits a close relationship with human beings. In this study, we isolated and purified 60 yeast strains from the natural fermentation broth of Sidamo coffee beans to screen for indigenous beneficial yeasts. Among them, 25 strains were obtained through morphological characterization on nutritional agar medium from Wallerstein Laboratory (WL), with molecular biology identifying Saccharomyces cerevisiae strain YBB-47 and the remaining 24 yeast strains identified as Pichia kudriavzevii. We investigated the fermentation performance, alcohol tolerance, SO2 tolerance, pH tolerance, sugar tolerance, temperature tolerance, ester production capacity, ethanol production capacity, H2S production capacity, and other brewing characteristics of YBB-33 and YBB-47. The results demonstrated that both strains could tolerate up to 3% alcohol by volume at a high sucrose mass concentration (400 g/L) under elevated temperature conditions (40 ℃), while also exhibiting a remarkable ability to withstand an SO2 mass concentration of 300 g/L at pH 3.2. Moreover, S. cerevisiae YBB-47 displayed a rapid gas production rate and strong ethanol productivity. whereas P. kudriavzevii YBB-33 exhibited excellent alcohol tolerance. Furthermore, this systematic classification and characterization of coffee bean yeast strains from the Sidamo region can potentially uncover additional yeasts that offer high-quality resources for industrial-scale coffee bean production.

Psychromicrobium Xiongbiense sp. nov., an Actinobacterium Isolated from Forest Soil.

A novel Gram-stain-positive, oval-shaped, and non-flagellated bacterial strain YIM S02556T was isolated from forest soil in Xiongbi Town, Shizong County, Qujing City, Yunnan Province, southwestern China. The strain exhibited high pairwise 16 S rRNA gene sequence similarity with Psychromicrobium lacuslunae (97.3%) and Psychromicrobium silvestre (96.3%). Strain YIM S02556T exhibited an average nucleotide identity (ANI) of 72.5% with P. lacuslunae IHBB 11,108T and 72.8% ANI with P. silvestre AK 20-18T. The digital DNA-DNA hybridization (dDDH) value between strain YIM S02556T and P. lacuslunae IHBB 11,108T was 20.2%, while with P. silvestre AK 20-18T, the dDDH value was 20.8%. Strain YIM S02556T exhibited optimal growth at 28 °C, pH 7.0, without NaCl. Growth occurred within 10-37 ℃, pH 5.0-8.0, and in the presence of up to 5% w/v NaCl concentration. The genome size was 3.1 Mbp with 64.2% G + C content. The predominant menaquinone was MK-8(H4). The major cellular fatty acid was anteiso-C15:0. Based on the polyphasic analysis, strain YIM S02556T (= KCTC 49,805T = CCTCC AB2020166T) represents a novel Psychromicrobium species in which the name Psychromicrobium xiongbiense sp.nov. was proposed.

[Risk factors for recurrence of childhood acute lymphoblastic leukemia after treatment with the Chinese Children's Cancer Group ALL-2015 protocol]. / CCCG-ALL-2015æ–¹æ¡ˆæ²»ç–—å„¿ç«¥æ€¥æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— å¤å‘çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence. METHODS: A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed. RESULTS: Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group (P>0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage (n=62, 42.5%) and the early stage (n=46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene (HR=4.177, 95%CI: 2.086-8.364, P<0.001) and minimal residual disease≥0.01% on day 46 (HR=2.013, 95%CI: 1.163-3.483, P=0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol. CONCLUSIONS: There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

A transcriptional landscape underlying sugar import for grain set in maize.

Developing seed depends on sugar supply for its growth and yield formation. Maize (Zea mays L.) produces the largest grains among cereals. However, there is a lack of holistic understanding of the transcriptional landscape of genes controlling sucrose transport to, and utilization within, maize grains. By performing in-depth data mining of spatio-temporal transcriptomes coupled with histological and heterologous functional analyses, we identified transporter genes specifically expressed in the maternal-filial interface, including (i) ZmSWEET11/13b in the placento-chalazal zone, where sucrose is exported into the apoplasmic space, and (ii) ZmSTP3, ZmSWEET3a/4c (monosaccharide transporters), ZmSUT1, and ZmSWEET11/13a (sucrose transporters) in the basal endosperm transfer cells for retrieval of apoplasmic sucrose or hexoses after hydrolysis by extracellular invertase. In the embryo and its surrounding regions, an embryo-localized ZmSUT4 and a cohort of ZmSWEETs were specifically expressed. Interestingly, drought repressed those ZmSWEETs likely exporting sucrose but enhanced the expression of most transporter genes for uptake of apoplasmic sugars. Importantly, this drought-induced fluctuation in gene expression was largely attenuated by an increased C supply via controlled pollination, indicating that the altered gene expression is conditioned by C availability. Based on the analyses above, we proposed a holistic model on the spatio-temporal expression of genes that likely govern sugar transport and utilization across maize maternal and endosperm and embryo tissues during the critical stage of grain set. Collectively, the findings represent an advancement towards a holistic understanding of the transcriptional landscape underlying post-phloem sugar transport in maize grain and indicate that the drought-induced changes in gene expression are attributable to low C status.

ABA-responsive AREB1/ABI3-1/ABI5 cascade regulates IAA oxidase gene SlDAO2 to inhibit hypocotyl elongation in tomato.

Hypocotyl elongation is dramatically influenced by environmental factors and phytohormones. Indole-3-acetic acid (IAA) plays a prominent role in hypocotyl elongation, whereas abscisic acid (ABA) is regarded as an inhibitor through repressing IAA synthesis and signalling. However, the regulatory role of ABA in local IAA deactivation remains largely uncharacterized. In this study, we confirmed the antagonistic interplay of ABA and IAA during the hypocotyl elongation of tomato (Solanum lycopersicum) seedlings. We identified an IAA oxidase enzyme DIOXYGENASE FOR AUXIN OXIDATION2 (SlDAO2), and its expression was induced by both external and internal ABA signals in tomato hypocotyls. Moreover, the overexpression of SlDAO2 led to a reduced sensitivity to IAA, and the knockout of SlDAO2 alleviated the inhibitory effect of ABA on hypocotyl elongation. Furthermore, an ABA-responsive regulatory SlAREB1/SlABI3-1/SlABI5 cascade was identified to act upstream of SlDAO2 and to precisely control its expression. SlAREB1 directly bound to the ABRE present in the SlDAO2 promoter to activate SlDAO2 expression, and SlABI3-1 enhanced while SlABI5 inhibited the activation ability of SlAREB1 by directly interacting with SlAREB1. Our findings revealed that ABA might induce local IAA oxidation and deactivation via SlDAO2 to modulate IAA homoeostasis and thereby repress hypocotyl elongation in tomato.

Classification of quantum correlation using deep learning.

Quantum correlation, as an intrinsic property of quantum mechanics, has been widely employed to test the fundamental physical principles and explore the quantum-enhanced technologies. However, such correlation would be drowned and even destroyed in the conditions of high levels of loss and noise, which drops into the classical realm and renders quantum advantage ineffective. Especially in low light conditions, conventional linear classifiers are unable to extract and distinguish quantum and classical correlations with high accuracy. Here we experimentally demonstrate the classification of quantum correlation using deep learning to meet the challenge in the quantum imaging scheme. We design the convolutional neural network to learn and classify the correlated photons efficiently with only 0.1 signal photons per pixel. We show that decreasing signal intensity further weakens the correlation and makes an accurate linear classification impossible, while the deep learning method has a strong robustness of such task with the accuracy of 99.99%. These results open up a new perspective to optimize the quantum correlation in low light conditions, representing a step towards diverse applications in quantum-enhanced measurement scenarios, such as super-resolution microscope, quantum illumination, etc.

Experimental 61-partite entanglement on a three-dimensional photonic chip.

Multipartite entanglements are essential resources for proceeding tasks in quantum information science and technology. However, generating and verifying them present significant challenges, such as the stringent requirements for manipulations and the need for a huge number of building-blocks as the systems scale up. Here, we propose and experimentally demonstrate the heralded multipartite entanglements on a three-dimensional photonic chip. Integrated photonics provide a physically scalable way to achieve an extensive and adjustable architecture. Through sophisticated Hamiltonian engineering, we are able to control the coherent evolution of shared single photon in the multiple spatial modes, dynamically tuning the induced high-order W-states of different orders in a single photonic chip. Using an effective witness, we successfully observe and verify 61-partite quantum entanglements in a 121-site photonic lattice. Our results, together with the single-site-addressable platform, offer new insights into the accessible size of quantum entanglements and may facilitate the developments of large-scale quantum information processing applications.

Experimental Boson Sampling Enabling Cryptographic One-Way Function.

Boson sampling is a computational problem, which is commonly believed to be a representative paradigm for attaining the milestone of quantum advantage. So far, massive efforts have been made to the experimental large-scale boson sampling for demonstrating this milestone, while further applications of the machines remain a largely unexplored area. Here, we investigate experimentally the efficiency and security of a cryptographic one-way function that relies on coarse-grained boson sampling, in the framework of a photonic boson-sampling machine fabricated by a femtosecond laser direct writing technique. Our findings demonstrate that the implementation of the function requires moderate sample sizes, which can be over 4 orders of magnitude smaller than the ones predicted by the Chernoff bound; whereas for numbers of photons n≥3 and bins d∼poly(m,n), the same output of the function cannot be generated by nonboson samplers. Our Letter is the first experimental study that deals with the potential applications of boson sampling in the field of cryptography and paves the way toward additional studies in this direction.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

The role of prophylactic antibiotics in elective inguinal tension-free hernia repair: A systematic review and meta-analysis.

Whether to use antibiotics to prevent surgical site infection in elective inguinal tension-free hernia repair has been controversial. To systematically evaluate the effect of prophylactic antibiotic application in elective inguinal tension-free hernia repair, we identified all published randomised controlled trials of the effect of prophylactic antibiotic application on elective inguinal tension-free hernia repair were collected by computer retrieval from the China National Knowledge Infrastructure; VIP Database; Wanfang Database; China Biomedical Literature Database; and PubMed, EMBASE and Cochrane Library databases. Meta-analysis was performed by RevMan 5.3 software. The meta-analysis showed that the total incidence of surgical site infections [P = 0.003] and the incidence of superficial surgical site infections [P = 0.004] in the antibiotic group (AG) were lower than those in the non-antibiotic group (NAG). There was no significant difference in the total incidence of postoperative infections [P = 0.06], deep surgical site infections [P = 0.26] and seroma [P = 0.52] between the AG and the NAG. Based on current evidence, the application of prophylactic antibiotics in elective inguinal tension-free hernia repair can prevent the total incidence of surgical site infections and that of superficial surgical site infections but cannot prevent the total incidence of postoperative infection events, incidence of deep surgical site infections and incidence of seroma.

[Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi].

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.

Rapid Point-of-Care Assay by SERS Detection of SARS-CoV-2 Virus and Its Variants.

Addressing the spread of coronavirus disease 2019 (COVID-19) has highlighted the need for rapid, accurate, and low-cost diagnostic methods that detect specific antigens for SARS-CoV-2 infection. Tests for COVID-19 are based on reverse transcription PCR (RT-PCR), which requires laboratory services and is time-consuming. Here, by targeting the SARS-CoV-2 spike protein, we present a point-of-care SERS detection platform that specifically detects SARS-CoV-2 antigen in one step by captureing substrates and detection probes based on aptamer-specific recognition. Using the pseudovirus, without any pretreatment, the SARS-CoV-2 virus and its variants were detected by a handheld Raman spectrometer within 5 min. The limit of detection (LoD) for the pseudovirus was 124 TU µL-1 (18 fM spike protein), with a linear range of 250-10,000 TU µL-1. Moreover, this assay can specifically recognize the SARS-CoV-2 antigen without cross reacting with specific antigens of other coronaviruses or influenza A. Therefore, the platform has great potential for application in rapid point-of-care diagnostic assays for SARS-CoV-2.

Reducing circuit complexity in optical quantum computation using 3D architectures.

Integrated photonic architectures based on optical waveguides are one of the leading candidates for the future realisation of large-scale quantum computation. One of the central challenges in realising this goal is simultaneously minimising loss whilst maximising interferometric visibility within waveguide circuits. One approach is to reduce circuit complexity and depth. A major constraint in most planar waveguide systems is that beamsplitter transformations between distant optical modes require numerous intermediate SWAP operations to couple them into nearest neighbour proximity, each of which introduces loss and scattering. Here, we propose a 3D architecture which can significantly mitigate this problem by geometrically bypassing trivial intermediate operations. We demonstrate the viability of this concept by considering a worst-case 2D scenario, where we interfere the two most distant optical modes in a planar structure. Using femtosecond laser direct-writing technology we experimentally construct a 2D architecture to implement Hong-Ou-Mandel interference between its most distant modes, and a 3D one with corresponding physical dimensions, demonstrating significant improvement in both fidelity and efficiency in the latter case. In addition to improving fidelity and efficiency of individual non-adjacent beamsplitter operations, this approach provides an avenue for reducing the optical depth of circuits comprising complex arrays of beamsplitter operations.

Generating Haar-Uniform Randomness Using Stochastic Quantum Walks on a Photonic Chip.

As random operations for quantum systems are intensively used in various quantum information tasks, a trustworthy measure of the randomness in quantum operations is highly demanded. The Haar measure of randomness is a useful tool with wide applications, such as boson sampling. Recently, a theoretical protocol was proposed to combine quantum control theory and driven stochastic quantum walks to generate Haar-uniform random operations. This opens up a promising route to converting classical randomness to quantum randomness. Here, we implement a two-dimensional stochastic quantum walk on the integrated photonic chip and demonstrate that the average of all distribution profiles converges to the even distribution when the evolution length increases, suggesting the 1-pad Haar-uniform randomness. We further show that our two-dimensional array outperforms the one-dimensional array of the same number of waveguide for the speed of convergence. Our Letter demonstrates a scalable and robust way to generate Haar-uniform randomness that can provide useful building blocks to boost future quantum information techniques.

Direct Observation of Dynamically Localized Quantum Optical States.

Quantum-correlated biphoton states play an important role in quantum communication and processing, especially considering the recent advances in integrated photonics. However, it remains a challenge to flexibly transport quantum states on a chip, when dealing with large-scale sophisticated photonic designs. The equivalence between certain aspects of quantum optics and solid-state physics makes it possible to utilize a range of powerful approaches in photonics, including topologically protected boundary states, graphene edge states, and dynamic localization. Optical dynamic localization allows efficient protection of classical signals in photonic systems by implementing an analogue of an external alternating electric field. Here, we report on the observation of dynamic localization for quantum-correlated biphotons, including both the generation and the propagation aspects. As a platform, we use sinusoidal waveguide arrays with cubic nonlinearity. We record biphoton coincidence count rates as evidence of robust generation of biphotons and demonstrate the dynamic localization features in both spatial and temporal space by analyzing the quantum correlation of biphotons at the output of the waveguide array. Experimental results demonstrate that various dynamic modulation parameters are effective in protecting quantum states without introducing complex topologies. Our Letter opens new avenues for studying complex physical processes using photonic chips and provides an alternative mechanism of protecting communication channels and nonclassical quantum sources in large-scale integrated quantum optics.

Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

The adipokine orosomucoid alleviates adipose tissue fibrosis via the AMPK pathway.

The excess deposition of underlying extracellular matrix (ECM) in adipose tissue is defined as adipose tissue fibrosis that is a major contributor to metabolic disorder such as obesity and type 2 diabetes. Anti-fibrosis therapy has received much attention in the treatment of metabolic disorders. Orosomucoid (ORM) is an acute-phase protein mainly produced by liver, which is also an adipokine. In this study, we investigated the effects of ORM on adipose tissue fibrosis and the potential mechanisms. We showed that ORM1-deficient mice exhibited an obese phenotype, manifested by excessive collagen deposition in adipose tissues and elevated expression of ECM regulators such as metalloproteinases (MMP-2, MMP-13, MMP-14) and tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-3). Administration of exogenous ORM (50 mg· kg-1· d-1, ip) for 7 consecutive days in high-fat diet (HFD)-fed mice and leptin receptor (LepR)-deficient db/db mice attenuated these abnormal expressions. Meanwhile, ORM administration stimulated AMP-activated protein kinase (AMPK) phosphorylation and decreased transforming growth factor-ß1 (TGF-ß1) level in adipose tissues of the mice. In TGF-ß1-treated 3T3-L1 fibroblasts, ORM (10 µg/mL) improved the impaired expression profiles of fibrosis-related genes, whereas a selective AMPK inhibitor dorsomorphin (1 µmol/mL) abolished these effects. Together, our results suggest that ORM exerts a direct anti-fibrosis effect in adipose tissue via AMPK activation. ORM is expected to become a novel target for the treatment of adipose tissue fibrosis.