Differential mRNA profiles reveal the potential roles of genes involved in lactate stimulation in mouse macrophages.

Lactate is a glycolysis end product, and its levels are markedly associated with disease severity, morbidity, and mortality in sepsis. It modulates key functions of immune cells, including macrophages. In this investigation, transcriptomic analysis was performed using lactic acid, sodium lactate, and hydrochloric acid-stimulated mouse bone marrow-derived macrophages (iBMDM), respectively, to identify lactate-associated signaling pathways. After 24 h of stimulation, 896 differentially expressed genes (DEG) indicated were up-regulation, whereas 792 were down-regulated in the lactic acid group, in the sodium lactate group, 128 DEG were up-regulated, and 41 were down-regulated, and in the hydrochloric acid group, 499 DEG were up-regulated, and 285 were down-regulated. Subsequently, clinical samples were used to further verify the eight genes with significant differences, among which Tssk6, Ypel4, Elovl3, Trp53inp1, and Cfp were differentially expressed in patients with high lactic acid, indicating their possible involvement in lactic acid-induced inflammation and various physiological diseases caused by sepsis. However, elongation of very long chain fatty acids protein 3 (Elovl3) was negatively correlated with lactic acid content in patients. The results of this study provide a necessary reference for better understanding the transcriptomic changes caused by lactic acid and explain the potential role of high lactic acid in the regulation of macrophages in sepsis.

Combining thermotherapy with shoot tip culture or cryotherapy for improved virus eradication from in vitro Actinidia macrosperma.

In recent years, kiwifruit viral diseases have become increasingly prevalent in kiwifruit producing regions of China, significantly impacting both the yield and quality of kiwifruit. This has emerged as a significant constraint on the healthy and sustainable development of the kiwifruit industry. The use of virus-free propagation materials has been proven to be an effective strategy for controlling plant viral diseases. In the present study, shoot tip culture (STC), shoot tip cryotherapy (Cryo), and their combinations with thermotherapy were established to eradicate AcVA, AcVB and AcCRaV from Actinidia macrosperma. Additionally, the impact of shoot tip size on virus eradication was evaluated. Among the three confirmed viruses, AcVB was the easiest to eradicate, followed by AcVA and AcCRaV. Combining thermotherapy with shoot tip culture or cryotherapy resulted in higher virus elimination rates than shoot tip culture or cryotherapy alone. Notably, the combination of thermotherapy and 0.5-1 mm shoot tip cryotherapy was shown to be the most effective protocol which produced 50% of regenerated shoots free from all the tested viruses. To the best of our knowledge, this is the first report on virus elimination from kiwifruit infected with multiple viruses based on conventional shoot tip culture and shoot tip cryotherapy.

Pharmacologic inhibition of IL11/STAT3 signaling increases MHC-I expression and T cell infiltration.

BACKGROUND: Recent studies have discovered an emerging role of IL11 in various colitis-associated cancers, suggesting that IL11 mainly promotes tumor cell survival and proliferation in regulating tumorigenesis. Herein we aimed to reveal a novel function of IL-11 through STAT3 signaling in regulating tumor immune evasion. METHODS: AOM/DSS model in Il11-/- and Apcmin/+/Il11-/- mice were used to detect tumor growth and CD8+ T infiltration. STAT1/3 phosphorylation and MHC-I, CXCL9, H2-K1 and H2-D1 expression were detected in MC38 cells and intestine organoids treated with/without recombinant IL11 to explore effect of IL11/STAT3 signaling, with IL11 mutein used to competitively inhibit IL11 and rescue inhibited STAT1 activation. Correlation between IL11 and CD8+ T infiltration was analyzed using TIMER2.0 website. IL11 expression and survival prognosis was analyzed in clinical data of patient cohort from Nanfang Hospital. RESULTS: IL11 is highly expressed in CRC and indicates unfavorable prognosis. IL11 knockout increased CD8+ T cell infiltration and reduced intestinal and colon formation. Tumors were significantly suppressed while MHC-I and CXCL9 expression for CD8+ T infiltration were remarkably increased in the tumor tissues of Apcmin/+/Il11-/- mice or Il11-/- mice induced by AOM/DSS. IL11/STAT3 signaling downregulated MHC-I and CXCL9 by inhibiting IFNγ-induced STAT1 phosphorylation. IL11 mutein competitively inhibit IL11 to upregulate CXCL9 and MHC-I in tumor and attenuated tumor growth. CONCLUSIONS: This study ascribes for a new immunomodulatory role for IL11 during tumor development that is amenable to anti-cytokine based therapy of colon cancer.

How seasonality affects the environmental performance of fresh appetite: Insights from cherry consumption in China.

Urbanization and globalization are changing the conventional constraints of seasonality and geography on food consumption, such as that of fresh cherries. The rising demand for year-round cherry consumption in China is currently satisfied by open-field, greenhouse-produced, and imported products. This study conducted a spatial-temporal life cycle evaluation of the environmental performance of cherry consumption behaviors during different seasons of the year. Moreover, based on the definitions of global and local seasonality, the additional environmental costs of out-of-season cherry consumption were estimated. Results show that seasonality was an important factor affecting the environmental burdens of cherry consumption. Eating cherries imported from Chile by air in October resulted in the highest greenhouse gas (GHG) emissions of 6.38 kg CO2-eq/kg, while eating domestic open-field cherries during May to July (the natural harvest season) was a relatively environmentally beneficial option. The total cherry consumption in China in 2019 generated GHG emissions of 126.99 × 104 t CO2-eq. Under the definitions of global and local seasonality, the out-of-season consumption led to additional environmental costs of 57.59 × 104 and 85.67 × 104 t CO2-eq, accounting for 45.35% and 67.46% of total emissions, respectively. Furthermore, the time-environment trade-off effect of cherry consumption illustrates the higher environmental costs are exchanged for satisfying the appetite for out-of-season fresh foods. Our findings emphasize the meaningful implications for developing a sustainable consumption pattern for all stakeholders involved in the entire food chain.

Exosomal microRNA-133b-3p from bone marrow mesenchymal stem cells inhibits angiogenesis and oxidative stress via FBN1 repression in diabetic retinopathy.

Diabetic retinopathy (DR) is a common microvascular complication. Many studies have focused on the role of microRNAs (miRNAs) in DR but not specifically on miR-133b-3p. Thus, this study is to unmask the mechanisms of miR-133b-3p in DR. KK/Upj-Ay mice (a spontaneous diabetic nephropathy model of DM, referred to as DR mice) were used in the study, and retinal tissues were collected. Bone marrow mesenchymal stem cells (BMSCs) were isolated and identified. High glucose (HG)-treated mouse retinal microvascular endothelial cells (mRMECs) were transfected or co-cultured with BMSCs-derived exosomes. Then, cell proliferation, migration, apoptosis, angiogenesis, and oxidative stress were observed. MiR-133b-3p and FBN1 expression in tissues and cells was detected. MiR-133b-3p expression was reduced, and FBN1 expression was increased in retinal tissues of DR mice and HG-treated mRMECs. Up-regulating miR-133b-3p or down-regulating FBN1 or BMSCs-derived exosomes impaired oxidative stress, angiogenesis, proliferation, migration, and promoted apoptosis of HG-treated mRMECs. This study has elucidated that exosomal miR-133b-3p from BMSCs suppresses angiogenesis and oxidative stress in DR via FBN1 repression.

Increasing disparities in the embedded carbon emissions of provincial urban households in China.

In the context of carbon neutrality and the National Economic Circle Strategy, understanding regional disparities in carbon emissions from household consumption is conducive to regional coordination as well as high-quality and low-carbon development in China. In this study, a multiregional input-output (MRIO) model and structural decomposition analysis (SDA) are adopted to investigate the regional disparity change trends of embedded carbon emissions (ECEs) from urban households and the underlying drivers during the rapid economic development period from 2002 to 2012 in China. The results indicate that the eastern regions tended to have larger increments in total urban household ECEs, while the western regions tended to have faster growth rates. An increasing disparity and evident outsourcing pattern can be observed during the study period. The consumption level had a strong positive effect on urban household ECEs in all of the provinces, while the carbon efficiency, consumption pattern, production structure, and population size had differentiated offsetting effects on urban household ECEs in various provinces. The results obtained in this study are conducive to promoting joint efforts for carbon emission reduction and narrowing regional disparities.

Confocal super-resolution microscopy based on a spatial mode sorter.

Spatial resolution is one of the most important specifications of an imaging system. Recent results in the quantum parameter estimation theory reveal that an arbitrarily small distance between two incoherent point sources can always be efficiently determined through the use of a spatial mode sorter. However, extending this procedure to a general object consisting of many incoherent point sources remains challenging, due to the intrinsic complexity of multi-parameter estimation problems. Here, we generalize the Richardson-Lucy (RL) deconvolution algorithm to address this challenge. We simulate its application to an incoherent confocal microscope, with a Zernike spatial mode sorter replacing the pinhole used in a conventional confocal microscope. We test different spatially incoherent objects of arbitrary geometry, and we find that the resolution enhancement of sorter-based microscopy is on average over 30% higher than that of a conventional confocal microscope using the standard RL deconvolution algorithm. Our method could potentially be used in diverse applications such as fluorescence microscopy and astronomical imaging.

Direct Tomography of High-Dimensional Density Matrices for General Quantum States of Photons.

Quantum-state tomography is the conventional method used to characterize density matrices for general quantum states. However, the data acquisition time generally scales linearly with the dimension of the Hilbert space, hindering the possibility of dynamic monitoring of a high-dimensional quantum system. Here, we demonstrate a direct tomography protocol to measure density matrices of photons in the position basis through the use of a polarization-resolving camera, where the dimension of density matrices can be as large as 580×580 in our experiment. The use of the polarization-resolving camera enables parallel measurements in the position and polarization basis and as a result, the data acquisition time of our protocol does not increase with the dimension of the Hilbert space and is solely determined by the camera exposure time (on the order of 10 ms). Our method is potentially useful for the real-time monitoring of the dynamics of quantum states and paves the way for the development of high-dimensional, time-efficient quantum metrology techniques.

Tunable electromagnetically induced transparency based on graphene metamaterials.

In this paper we propose a graphene-based metasurface structure that can exhibit tunable electromagnetically-induced-transparency-like (EIT) spectral response at mid-infrared frequencies. The metasurface structure is composed of two subwavelength mono-layer graphene nano-disks coupled with a mono-layer graphene nano-strip. We show that the coupling of the nano-disks' dipole resonance with the quadrupole resonance of the nano-strip can create two split resonances with a transparency window in between at any desired center frequency within a wide frequency range. We show that such an EIT-like response can also be dynamically shifted in frequency by adjusting the Fermi-level of the graphene through external voltage control, which provides convenient post-fabrication tunability. In addition, the performance of such a metastructure for sensing the refractive index of the surrounding medium is analyzed. The simulation results show that its sensitivity can reach 3016.7 nm/(RIU) with a FOM exceeding 12.0. Lastly, we present an analysis of the slow light characteristics of the proposed device, where the group index can reach as large as 200. Our design provides a new miniaturized sensing platform that can facilitate the development of biochemical molecules testing, etc.

Retracted: MicroRNA-373 promotes the development of endometrial cancer by targeting LATS2 and activating the Wnt/ß-Catenin pathway.

In the female reproductive tract, endometrial cancer is the most common malignant tumor. Recently, the specific functions of many miRNAs have been identified in endometrial cancer. However, the contradictory effects of microRNA-373 (miR-373) in different human cancers draw our attention. In the present research, upregulation of miR-373 was identified in endometrial cancer which predicted poor prognosis. Moreover, upregulation of miR-373 promoted the migration, invasion, and proliferation of endometrial cancer cells. To further confirm that results, the EMT and Wnt/ß-Catenin pathways were also investigated, which were promoted by overexpression of miR-373. Then, we further investigate the downstream factor, large tumor suppressor kinase 2 (LATS2) which was inhibited by miR-373. LATS2 was verified as a direct target gene of miR-373 through luciferase reporter assay. Especially, the facilitation of miR-373 for cell proliferation, migration and invasion was impaired by LATS2. Taken together, miR-373 promotes the progression of endometrial cancer through targeting LATS2 and promoting EMT and Wnt/ß-Catenin pathway.

Type 1 IFN signaling critically regulates influenza-induced alloimmunization to transfused KEL RBCs in a murine model.

BACKGROUND: Only a fraction of red blood cell (RBC) transfusion recipients form alloantibodies, and variables determining responsiveness or nonresponsiveness are poorly understood. We and others have previously shown in animal models that pretreatment with toll-like receptor agonists that mimic different types of infections impacts the magnitude or frequency of RBC alloantibody responses. We hypothesized that influenza infection, coexistent with transfusion, would impact responses to transfused RBCs in a manner dependent on Type 1(α/ß) interferon (IFN) signaling and tested this in a murine model. STUDY DESIGN AND METHODS: Wild-type mice or mice lacking the ability to respond to Type 1 IFN were infected with influenza prior to the transfusion of transgenic murine RBCs (K1) expressing the human KEL glycoprotein or the triple fusion HOD protein. Alloantibody responses were measured longitudinally after transfusion by flow cytometric crossmatch, and posttransfusion RBC recovery and survival was evaluated. RESULTS: Influenza-infected mice transfused with K1 RBCs developed robust anti-KEL alloantibodies, whereas animals transfused in the absence of infection remained nonresponders; influenza-associated RBC alloimmunization was also observed after transfusion of HOD RBCs. Recipient Type 1 IFN production was critical to the mechanism of action of influenza-induced RBC alloimmunization, with alloimmunization being significantly decreased in mice unable to sense Type 1 IFN (through antibody blockade or genetic approaches). CONCLUSION: These and other data suggest that Type 1 IFN responses to toll-like receptor agonists or infections regulate RBC alloantibody responses. Studies investigating whether such a correlation exists in humans may be informative.

Increased antitumor activities of glypican-3-specific chimeric antigen receptor-modified T cells by coexpression of a soluble PD1-CH3 fusion protein.

Our recent clinical study demonstrated that glypican-3 (GPC3)-specific chimeric antigen receptor-modified T (CAR-T) cells are a promising treatment for hepatocellular carcinoma (HCC). However, the interaction of programmed cell death 1 (PD-1) and PD-L1-mediated T-cell inhibition is involved in immune evasion in a wide range of solid tumors, including HCC. To overcome this problem, we introduced a fusion protein composed of a PD-1 extracellular domain and CH3 from IgG4 into GPC3-specific CAR-T cells (GPC3-28Z) to block the PD-1/PD-L1 pathway. GPC3-specific CAR-T cells carrying the PD-1-CH3 fusion protein (sPD1) specifically recognized and lysed GPC3-positive HCC cells. The proliferation capacity of GPC3-28Z-sPD1 T cells after weekly stimulation with target cells was much higher than that of control GPC3-28Z T cells. Additionally, the coexpression of sPD1 could protect CAR-T cells from exhaustion when incubated with target cells, as phosphorylated AKT and Bcl-xL expression levels were higher in GPC3-28Z-sPD1 T cells than in GPC3-28Z cells. Importantly, in two HCC tumor xenograft models, GPC3-28Z-sPD1 T cells displayed a significantly higher tumor suppression capacity than GPC3-28Z T cells. In addition, an increased number of CD3+ T cells in the circulation and tumors and increased granzyme B levels and decreased Ki67 expression levels in the tumors were observed in the mice treated with GPC3-28Z-sPD1 T cells. Together, these data indicated that GPC3-specific CAR-T cells carrying sPD1 show promise as a treatment for patients with HCC.

Realization of a scalable Laguerre-Gaussian mode sorter based on a robust radial mode sorter.

The transverse structure of light is recognized as a resource that can be used to encode information onto photons and has been shown to be useful to enhance communication capacity as well as resolve point sources in superresolution imaging. The Laguerre-Gaussian (LG) modes form a complete and orthonormal basis set and are described by a radial index p and an orbital angular momentum (OAM) index ℓ. Earlier works have shown how to build a sorter for the radial index p or/and the OAM index ℓ of LG modes, but a scalable and dedicated LG mode sorter which simultaneous determinate p and ℓ is immature. Here we propose and experimentally demonstrate a scheme to accomplish complete LG mode sorting, which consists of a novel, robust radial mode sorter that can be used to couple radial modes to polarizations, an ℓ-dependent phase shifter and an OAM mode sorter. Our scheme is in principle efficient, scalable, and crosstalk-free, and therefore has potential for applications in optical communications, quantum information technology, superresolution imaging, and fiber optics.

Realization of a flat-band superprism on-chip from parallelogram lattice photonic crystals.

By optimizing the dispersion curve of a parallelogram-based 2D photonic crystal superprism for constant angular group velocity dispersion over a broad bandwidth, we designed a device capable of experimentally demonstrating linear dispersion from 1500 to 1600 nm with clear separation of as many as eight channels, while maintaining a compact footprint.

Hermite-Gaussian mode sorter.

The Hermite-Gaussian (HG) modes, sometimes referred to as transverse electromagnetic modes in free space, form a complete and orthonormal basis that have been extensively used to describe optical fields. In addition, these modes have been shown to be helpful in enhancing information capacity of optical communications as well as achieving super-resolution imaging in microscopy. Here we propose and present the realization of an efficient, robust mode sorter that can sort a large number of HG modes based on the relation between HG modes and Laguerre-Gaussian (LG) modes. We experimentally demonstrate the sorting of 16 HG modes, and our method can be readily extended to a higher-dimensional state space in a straightforward manner. We expect that our demonstration will have direct applications in a variety of fields including fiber optics, classical and quantum communications, as well as super-resolution imaging.

A Fusion Receptor as a Safety Switch, Detection, and Purification Biomarker for Adoptive Transferred T Cells.

The incorporation of an endogenous safety switch represents a rational strategy for the control of toxicities following the administration of adoptive T cell therapies. An ideal safety switch should be capable of depleting the transferred T cells with minimal injury to normal tissues. We generated a fusion receptor by engineering a cryptic 806 epitope of human epidermal growth factor receptor (EGFR) into the N terminus of the full-length human folate receptor 1 (FOLR1), designated as FR806. The expression of FR806 allows transduced T cells to be targeted with CH12, a monoclonal antibody recognizing the 806 epitope, but not wild-type EGFR in healthy tissues. FR806, therefore, constitutes a specific cell-surface marker for the elimination of transduced T cells. We demonstrate that the antibody-drug conjugate (ADC) CH12-MMAF is efficiently internalized by FR806-expressing T cells and has the potential to eliminate them. Transfected T cells could, furthermore, be efficiently detected and purified using CH12 antibodies. In immuno-compromised mice, CH12-MMAF eliminated the majority of transferred T cells expressing FR806 and anti-CD19 chimeric antigen receptor (CAR). The selectivity for the 806 epitope and internalization capacity of FOLR1 makes FR806 an efficient safety switch, which may additionally be used as a detection and purification biomarker for human T cell immunotherapies.

Overexpression miR-211-5p hinders the proliferation, migration, and invasion of thyroid tumor cells by downregulating SOX11.

PURPOSE: This study was aimed to investigate the relationship between miR-211-5p and SOX11, and the effects of their interaction on the proliferation, viability, and invasion of human thyroid cancer (TC) cells. METHODS: We used quantitative real-time PCR (qRT-PCR) to determine the expression of miR-211-5p and SOX11mRNA in the thyroid tumorous and the adjacent tissues. The target relationship between miR-211-5p and SOX11 was confirmed using dual luciferase reporter gene assay. Flow cytometry, colony formation assay, Transwell assay, and MTT assay were performed to determine the cell-cycle progression, cell apoptosis, proliferation and invasion, respectively. In addition, the tumor formation assay in nude mice was done to assess the effect of miR-211-5p on TC development in vivo. RESULTS: MiR-211-5p was underexpressed, whereas SOX11 was overexpressed in TC. The overexpression of miR-211-5p inhibited the expression of SOX11. The cell cycle was arrested and the proliferation as well as invasiveness was suppressed by exogenous miR-211-5p in TC cell line. The antitumor role of miR-211-5p was proved by the animal experiment. CONCLUSION: MiR-211-5p affected the viability, proliferation and invasion of TC by negatively regulating SOX11 expression.

Upregulation of miR-191 promotes cell growth and invasion via targeting TIMP3 in prostate cancer.

PURPOSE: Prostate cancer (PCa) is the most frequently malignant neoplasm in men. MicroRNAs (miRs) have been identified to play important biological roles in a variety of tumors. Several studies showed that miR-191 was involved in the development of different cancers, but its role in prostate cancer remains unclear. METHODS: Human PCa cell lines DU145, PC-3 and LNCAP, and benign prostate hyperplasia (BPH) and human prostate epithelial cell line RWPE-1 were used. The expression level of miR-191 in 48 paired prostate tumor and adjacent normal tissues was assessed along with the clinical patient features. Synthetic miR-191 mimics and inhibitors were used to overexpress or inhibit the miR-191 level. CCK8 and colony formation assay were used to evaluate the cell growth. The ability of cell invasion was studied by transwell assay. Dual-luciferase experiment was used to identify the target gene and western blot was performed to evaluate the protein level. RESULTS: miR-191 was overexpressed in PCa tissue samples compared to the normal group as well in PCa-derived cell lines. Upregulation miR-191 in PC-3 cells significantly promoted while downregulation miR-191 in DU145 cells retarded the cell proliferation and invasion. Furthermore, TIMP3 were proved to be a direct target gene of miR-191 and knockdown of TIMP3 reversed the function of miR-191 downregulation. CONCLUSION: This study demonstrated that miR-191 promoted the cell growth and invasion ability in prostate cancer through downregulating TIMP3 and might be a potential target for the biotherapy for PCa.

Spectral shift of a light wave on scattering from an ellipsoidal particle with arbitrary orientation.

Within the accuracy of the first-order Born approximation, a general expression for the far-zone spectrum of a light wave on scattering from an arbitrarily orientated ellipsoidal particle is derived. We show that the spectrum of the scattered field, in general, changes with the scattering azimuthal angle, displaying rotational nonsymmetry. The influence of the orientation of the particle on the spectrum of the scattered field is discussed, and the relationship between the orientation of scattering particle and the distribution of the relative spectral shift of the scattered field is investigated.

Antenatal Sonographic Diagnosis and Clinical Significance of Placenta Previa Accreta after Cesarean Section.

Objective To investigate the clinical and antenatal sonographic characteristics of placenta previa accreta after cesarean section. Methods The data of 21 inpatients diagnosed as placenta previa accreta after cesarean section in PUMC Hospital from 2006 to 2016 were retrospectively reviewed. The clinical and ultrasound features were recorded and compared among three placental accreta groups,including placenta accrete group(n=5),increta group(n=12),and percreta group(n=4). The relationship between the placental thickness at the uterine anterior lower segment level and the blood loss of the following cesarean section was tested. Results Of 21 patients,placenta previa was diagnosed by ultrasound in 20 cases(95.2%) and placenta previa accreta was diagnosed in 9 cases(42.9%). Antenatal ultrasound findings included following signs:loss of "clear zone"(15/18,83.3%),myometrial thinning(12/18,66.7%),abnormal placental lacunae(12/19,63.2%),bladder wall interruption(2/18,11.1%),and uterovesical hypervascularity(4/9,44.4%). Myometrial thinning(J-T=64.000,P=0.036),abnormal placental lacunae(J-T=74.500,P=0.032) and the placental thickness at the uterine anterior lower segment level(U=83.000,P=0.010) showed significant difference among different placenta accreta groups. Placental thickness at the uterine anterior lower segment level showed linear correlation with the blood loss of the following cesarean section(r=0.669,P=0.002). The blood loss of the following cesarean section showed significant difference among different placenta accreta groups(U=118.500,P=0.000). Conclusions The clinical and sonographic manifestations of placenta previa accreta after cesarean section show a spectrum of demographic characteristics. The measurement of thickness of placenta at the anterior lower segment may help the evaluation of the clinical prognosis of this special pathology.