Re-expression of epigenetically silenced PTPRR by histone acetylation sensitizes RAS-mutant lung adenocarcinoma to SHP2 inhibition.

Silenced protein tyrosine phosphatase receptor type R (PTPRR) participates in mitogen-activated protein kinase (MAPK) signaling cascades during the genesis and development of tumors. Rat sarcoma virus (Ras) genes are frequently mutated in lung adenocarcinoma, thereby resulting in hyperactivation of downstream MAPK signaling. However, the molecular mechanism manipulating the regulation and function of PTPRR in RAS-mutant lung adenocarcinoma is not known. Patient records collected from the Cancer Genome Atlas and Gene Expression Omnibus showed that silenced PTPRR was positively correlated with the prognosis. Exogenous expression of PTPRR suppressed the proliferation and migration of lung cancer cells. PTPRR expression and Src homology 2 containing protein tyrosine phosphatase 2 (SHP2) inhibition acted synergistically to control ERK1/2 phosphorylation in RAS-driven lung cancer cells. Chromatin immunoprecipitation assay revealed that HDAC inhibition induced enriched histone acetylation in the promoter region of PTPRR and recovered PTPRR transcription. The combination of the HDAC inhibitor SAHA and SHP2 inhibitor SHP099 suppressed the progression of lung cancer markedly in vitro and in vivo. Therefore, we revealed the epigenetic silencing mechanism of PTPRR and demonstrated that combination therapy targeting HDAC and SHP2 might represent a novel strategy to treat RAS-mutant lung cancer.

Enfortumab-vedotin use for urothelial carcinoma in two patients on hemodialysis.

Enfortumab vedotin (EV) is a novel treatment option for patients with advanced/metastatic urothelial carcinoma who have progressed after chemotherapy and immunotherapy. Two patients at two different New England tertiary cancer care centers were treated with EV while concurrently receiving hemodialysis (HD), where a complete response to EV in both patients was noted. The use of EV in patients requiring HD is extrapolated from the available pharmacokinetic and pharmacodynamic literature on monoclonal antibodies in patients requiring HD. There is a paucity of data for the use of antibody-drug conjugates like EV in patients needing dialysis.

Electrically driven supersymmetric semiconductor laser arrays with single-lobe far-field patterns.

Semiconductor laser arrays based on the third-order supersymmetric (SUSY) transformation are proposed to increase the mode discrimination between fundamental supermode and high-order supermodes. The distance between the edge waveguide of the main array and that of the superpartners is optimized. Then, the electric field distributions of different modes are also calculated, which show that, except for the fundamental supermode, the high-order supermodes penetrate deeper into the superpartner arrays, which accounts for the increased loss of high-order supermodes. The fabricated third-order SUSY laser array can emit light with a single-lobe far-field pattern under an injection current of 70 mA, which is a promising candidate for optical couplings between lasers and optical elements.

The genetic secrets of adaptation: decoding the significance of the 30-bp insertion in the KRT77 gene for Chinese cattle.

The KRT77 gene is a type II epithelial cell α-keratin gene family member that plays a crucial role in animal epidermal and coat formation. This study aimed to investigate the relationship between the KRT77 gene and the adaptability of Chinese cattle in varying environments by exploring the distribution of an exon insertion of the KRT77 gene in different cattle populations. Our analysis involved amplifying and sequencing DNA samples from 362 individuals from 24 cattle breeds in China. Our findings reveal a gradual increase in the frequency of insertion from the northwest to the southeast population. We conducted an association analysis between the genotypes and climate data, revealing a correlation between the insertion and local annual mean temperature, relative humidity, and temperature humidity index. The study highlights the significance of the newly identified KRT77 gene insertion as a variation associated with environmental adaptation in Chinese cattle.This insertion variation increased insights into the genetic mechanisms that drive adaptation in Chinese cattle, emphasizing the importance of the 30-bp insertion in the KRT77 gene. Our findings facilitate further research to improve cattle breeding strategies for adaptability to changing environments from the northwest to the southeast population. In conclusion, this study provides value.

SHMT2 Promotes Gastric Cancer Development through Regulation of HIF1α/VEGF/STAT3 Signaling.

The metabolic enzymes involved in one-carbon metabolism are closely associated with tumor progression and could be potential targets for cancer therapy. Recent studies showed that serine hydroxymethyltransferase 2 (SHMT2), a crucial enzyme in the one-carbon metabolic pathway, plays a key role in tumor proliferation and development. However, the precise role and function of SHMT2 in gastric cancer (GC) remain poorly understood. In this study, we presented evidence that SHMT2 was necessary for hypoxia-inducible factor-1α (HIF1α) stability and contributed to GC cells' hypoxic adaptation. The analysis of datasets retrieved from The Cancer Genome Atlas and the experimentation with human cell lines revealed a marked increase in SHMT2 expression in GC. The SHMT2 knockdown in MGC803, SGC7901, and HGC27 cell lines inhibited cell proliferation, colony formation, invasion, and migration. Notably, SHMT2 depletion disrupted redox homeostasis and caused glycolytic function loss in GC cells under hypoxic circumstances. Mechanistically, we discovered SHMT2 modulated HIF1α stability, which acted as a master regulator of hypoxia-inducible genes under hypoxic conditions. This, in turn, regulated the downstream VEGF and STAT3 pathways. The in vivo xenograft experiments showed that SHMT2 knockdown markedly reduced GC growth. Our results elucidate the novel function of SHMT2 in stabilizing HIF1α under hypoxic conditions, thus providing a potential therapeutic strategy for GC treatment.

Polygonum orientale L. Alleviates Myocardial Ischemia-Induced Injury via Activation of MAPK/ERK Signaling Pathway.

Although Polygonum orientale L. (PO) has a beneficial effect on treatment of myocardial ischemia (MI), its mechanism remains unclear. This study aimed to explore the pharmacological mechanism of PO against MI through MAPK signaling pathways. Firstly, the therapeutic effect of PO was evaluated for treatment of MI mice. Using Western blot and immunohistochemistry, the influence of PO on MAPK signaling pathways and cell apoptosis was investigated. Subsequently, one key pathway (ERK) of MAPK signaling pathways was screened out, on which PO posed the most obvious impact. Finally, an inhibitor of ERK1/2 was utilized to further verify the regulatory effect of PO on the MAPK/ERK signaling pathway. It was found that PO could reduce the elevation of the ST segment; injury of heart tissue; the activity of LDH, CK, NOS, cNOS and iNOS and the levels of NO, BNP, TNF-α and IL-6. It is notable that PO could significantly modulate the protein content of p-ERK/ERK in mice suffering from MI but hardly had an effect on p-JNK/JNK and p-p38/p38. Additionally, the expressions of bax, caspase3 and caspase9 were inhibited in heart tissue in the PO-treated group. To evaluate whether ERK1/2 inhibitor (PD98059) could block the effect of PO on treatment of MI, both PO and PD98059 were given to mice with MI. It was discovered that the inhibitor indeed could significantly reverse the regulatory effects of PO on the above indicators, indicating that PO could regulate p-ERK/ERK. This study provides experimental evidence that PO extenuates MI injury, cardiomyocyte apoptosis and inflammation by activating the MAPK/ERK signaling pathway.

Different phases in non-Hermitian topological semiconductor stripe laser arrays.

As a novel branch of topology, non-Hermitian topological systems have been extensively studied in theory and experiments recently. Topological parity-time (PT)-symmetric semiconductor stripe laser arrays based on the Su-Schreiffer-Heeger model are proposed. The degree of non-Hermicity can be tuned by altering the length of the cavities, and PT symmetry can be realized by patterned electrode. Three laser arrays working in different non-Hermitian phases are analyzed and fabricated. With the increasing degree of non-Hermicity, the peaks of output intensities move from the edge to the bulk. The proposed semiconductor stripe laser array can function as an active, flexible, and feasible platform to investigate and explore non-Hermitian topology for further developments in this field.

Single-chip hybrid integrated silicon photonics transmitter based on passive alignment.

A single-chip hybrid integrated silicon photonics transmitter based on passive alignment flip-chip bonding technology has been demonstrated. The transmitter is developed by the hybrid integration of a C-band slotted laser with 1 mm cavity length and a Mach-Zehnder modulator with 2 mm long phase shifter. A 3 dB bandwidth of the small signal response is 16.35 GHz at 5.99 VPP superimposed with a reverse bias voltage of 2.43 V. A 25 Gbps data transmission experiment of the hybrid integrated transmitter is performed at 25°C.

Electrically injected supersymmetric semiconductor lasers with narrow vertical divergence angle.

Electrically injected supersymmetric (SUSY) semiconductor lasers are proposed and fabricated. Two successive SUSY transformations are applied to the main array arranged along the direction of epitaxial growth, which can remove the propagation constants of the fundamental mode and the leaky mode of the main array from the superpartner while keeping those of other high-order modes. The SUSY laser possesses an excellent mode discrimination and favors the lasing of the fundamental mode. The fabricated SUSY laser can emit light with a single-lobe vertical far-field pattern with the full width at half maximum of 16.87° under an injection current of 1.4 A.

Using Micro-Raman Spectroscopy to Investigate Chemical Composition, Mixing States, and Heterogeneous Reactions of Individual Atmospheric Particles.

Measuring the chemical composition of individual atmospheric aerosol particles can provide direct evidence of their heterogeneous reactions and mixing states in the atmosphere. In this study, micro-Raman spectroscopy was used to measure the chemical composition of 1200 individual atmospheric particles in 11 samples collected in Beijing air. (NH4)2SO4, NH4NO3, various minerals, carbonaceous species (soot and organics), and NaNO3 were identified in the measured particles according to their characteristic Raman peaks. These species represented the main components of aerosol particles. In individual particles, NH4NO3 and (NH4)2SO4 either existed separately or were internally mixed. Possible reaction pathways of CaCO3 particles in the atmosphere were proposed based on the results of this study and laboratory simulations on heterogeneous reactions in the literature. CaCO3 reacted with N- and S-containing (nitrogen- and sulfur-containing) acidic gases to produce Ca(NO3)2 and CaSO4. Ca(NO3)2 further reacted with S-containing acidic gases and oxidants to produce CaSO4. Of the soot-containing particles, 23% were internal mixtures of soot and inorganic material. Of the organics-containing particles, 57% were internal mixtures of organic and inorganic materials. Micro-Raman spectroscopy directly identified functional groups and molecules in individual atmospheric particles under normal ambient conditions, rendering it a powerful tool for measuring the chemical composition of individual atmospheric particles with a diameter of ≥1.0 µm.

[Intestinal absorption characteristics of Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats via everted intestinal sac models].

The present study is to investigate the absorption characteristics of the main components in Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats with everted intestinal sac models. Intestinal sac fluid samples were collected in different part of intestine(duodenum, jejunum, ileum, colon) at different time after administration of different concentration of P. orientale extract(5.0,10.0, 20.0 mg·mL~(-1)). An UPLC-TQD method was employed for the determination of six components including orientin, isoorientin, vitexin, protocatechuic acid, kaempferol-3-O-ß-D-glucoside and quercitrin in the intestinal sac samples. The absorption rate and cumulative absorption were calculated to analyze the intestinal absorption characteristics of six components in normal and myocardial ischemia model rats. The P-glycoprotein(P-gp) inhibitor was applied to investigate influence of intestinal absorption of six components in P. orientale extract. The results showed that the main absorption sites were concentrated on the duodenum at low concentration, while they were the colon at the medium concentration and the ileum at high concentration in control groups. In the condition of myocardial ischemia model, the main absorption sites focus on the ileum and jejunum at low concentration; the main absorption sites were in the ileum at the medium concentration and main absorption sites were the duodenum and ileum at high concentration. Compared with the normal group, the absorption rate and cumulative absorption of the six components significantly decreased in the model group. P-gp inhibitor markedly increased the absorption rate and cumulative absorption of six components in the model group, inferring that the 6 components may be the substrates of P-gp, and the mechanism needs further study. In this study, it is revealed that the six components of P. orientale extract can be absorbed into the intestinal sac, and it is an effective method to assess the intestinal absorption characteristics of P. orientale extract through everted intestinal sac model, providing data support for the clinical application and further development of P. orientale.

Single-mode semiconductor lasers fabricated by standard photolithography for direct modulation.

The output characteristics, modal properties, far-field profiles, and dynamic modulation responses of semiconductor lasers with surface higher-order gratings fabricated by the standard photolithography are presented. Single-mode semiconductor lasers with 20th- and 37th-order gratings for the 1.55 µm wavelength range are realized. The single-mode semiconductor lasers with 20th-order gratings have lower threshold currents and higher slope efficiencies than those with 37th-order gratings. The surface higher-order grating placed closed to the output facet can deteriorate the vertical far-field profile of the semiconductor laser. However, the properties of the semiconductor laser's single-mode operation are not affected by the surface higher-order grating's position in the ridge waveguide. The -3 dB bandwidth of these single-mode semiconductor lasers can achieve 9 GHz at 100 mA, which is the highest, to the best of our knowledge, for such a kind of single-mode semiconductor laser with a surface higher-order grating.

High-power high-brightness 980 nm lasers with >50% wall-plug efficiency based on asymmetric super large optical cavity.

High-power high-brightness super large optical cavity laser diodes with an optimized epitaxial structure are investigated at the wavelength of 980 nm range. The thicknesses of P- and N-waveguides are prudently chosen based on a systematic consideration about mode characteristics and vertical far-field divergences. Broad area laser diodes show a high internal quantum efficiency of 98% and a low internal optical loss of 0.58 cm-1. The ridge-waveguide laser with 7 µm ridge and 3 mm cavity yields 1.9 W single spatial mode output with far-field divergence angles of 6.8° in lateral and 11.5° in vertical at full width at half maximum under 2 A CW operating current. The corresponding M2 values are 1.77 and 1.47 for lateral and vertical, respectively, and the corresponding brightness is 76.8 MW‧cm-2‧sr-1. The far-field divergence angles with 95% power content are in the range of 24.7° to 26.1° across the whole measured range.

Eight-channel laser array with 100 GHz channel spacing based on surface-slotted structures fabricated by standard lithography.

An eight-channel laser array with 100 GHz channel spacing based on surface-slotted structures is demonstrated. Wavelength selection is realized by using a group of micrometer-order slots fabricated by standard lithography technology. An output power of over 14 mW and a side-mode suppression ratio of better than 35 dB for each laser within the array are achieved. A laser array without tuning for 100 GHz channel spacing by standard lithography was realized for the first time, to the best of our knowledge. The laser array can be used to enhance the capacity of communication links and provides a promising light source for photonic-integrated circuits.

Using X-ray computed tomography and micro-Raman spectrometry to measure individual particle surface area, volume, and morphology towards investigating atmospheric heterogeneous reactions.

Heterogeneous reactions on the aerosol particle surface in the atmosphere play important roles in air pollution, climate change, and global biogeochemical cycles. However, the reported uptake coefficients of heterogeneous reactions usually have large variations and may not be relevant to real atmospheric conditions. One of the major reasons for this is the use of bulk samples in laboratory experiments, while particles in the atmosphere are suspended individually. A number of technologies have been developed recently to study heterogeneous reactions on the surfaces of individual particles. Precise measurements on the reactive surface area, volume, and morphology of individual particles are necessary for calculating the uptake coefficient, quantifying reactants and products, and understanding the reaction mechanism better. In this study, for the first time we used synchrotron radiation X-ray computed tomography (XCT) and micro-Raman spectrometry to measure individual CaCO3 particle morphology, with sizes ranging from 3.5-6.5µm. Particle surface area and volume were calculated using a reconstruction method based on software three-dimensional (3-D) rendering. The XCT was first validated with high-resolution field-emission scanning electron microscopy (FE-SEM) to acquire accurate CaCO3 particle surface area and volume estimates. Our results showed an average difference of only 6.1% in surface area and 3.2% in volume measured either by micro-Raman spectrometry or X-ray tomography. X-ray tomography and FE-SEM can provide more morphological details of individual CaCO3 particles than micro-Raman spectrometry. This study demonstrated that X-ray computed tomography and micro-Raman spectrometry can precisely measure the surface area, volume, and morphology of an individual particle.

CHOROIDAL THICKNESS IN HEALTHY CHINESE CHILDREN AGED 6 to 12: The Shanghai Children Eye Study.

PURPOSE: To explore the characteristics of choroidal thickness (ChT) in Chinese children. METHODS: A total of 144 healthy children, aged 6 years to 12 years old, were enrolled in the study. The ChT of subfovea and peripheral locations 0.5, 1.5, and 2.5 mm away from the fovea were evaluated by enhanced depth imaging optical coherence tomography. The association between subfoveal ChT and systemic, as well as ocular factors, including age, sex, height, weight, body mass index, axial length, refractive error, intraocular pressure, preterm history, and the refractive status of parents were studied. RESULTS: The mean subfoveal ChT was 302 ± 63 µm. In the nasal, superior, and inferior areas, the ChT of locations closer to the fovea was thicker than those farther away from the fovea (all P < 0.05); however, ChT was not significantly different among different locations in the temporal area (P = 0.16). The ChT of the nasal quadrant was significantly thinner than that of other areas (P < 0.01). Subfoveal ChT decreased with age, axial length, preterm history, and increased with height. Sex was not statistically associated with subfoveal ChT. CONCLUSION: In Chinese children, the ChT is thinnest in the nasal quadrant and thicker in central regions than in peripheral areas. The subfoveal ChT independently decreases with age, axial length, preterm history, and increases with height.

PSAT1 mediated EMT of colorectal cancer cells by regulating Pl3K/AKT signaling pathway.

Background: The metastasis of colorectal cancer (CRC) is one of the significant barriers impeding its treated consequence and bring about high mortality, less surgical resection rate and poor prognosis of CRC patients. PSAT1 is an enzyme involved in serine biosynthesis. The studies showed that PSAT1 plays the part of a crucial character in the regulation of tumor metastasis. And Epithelial-Mesenchymal Transition (EMT) is a process of cell reprogramming in which epithelialcells obtain mesenchymal phenotypes. It is a crucial course in promoting cell metastasis and the progression of malignant tumors. The relationship between PSAT1 and EMT in colorectal cancer, as well as the underlying molecular mechanisms, remains enigmatic and warrants thorough exploration. These findings suggest that PSAT1 may serve as a promising therapeutic target for mitigating colorectal cancer metastasis and holds the potential to emerge as a valuable prognostic biomarker in forthcoming research endeavors. Materials and Methods: Utilizing TCGA dataset in conjunction with clinical CRC specimens, our initial focus was directed towards an in-depth examination of PSAT1 expression within CRC, specifically exploring its potential correlation with the adverse prognostic outcomes experienced by patients. Furthermore, we conducted a comprehensive investigation into the regulatory influence exerted by PSAT1 on CRC through the utilization of siRNA knockdown techniques. In the realm of in vitro experimentation, we meticulously evaluated the impact of PSAT1 on various facets of CRC progression, including cell migration, invasion, proliferation, and colony formation. In order to elucidate the intricate effects in question, we adopted a multifaceted methodology that encompassed a range of assays and analyses. These included wound healing assays, transwell assays, utilization of the Cell Counting Kit-8 (CCK-8) assay, and colony formation assays. By employing this diverse array of investigative techniques, we were able to achieve a comprehensive comprehension of the multifaceted role that PSAT1 plays in the pathogenesis of colorectal cancer. This multifarious analysis greatly contributed to our in-depth understanding of the complex mechanisms at play in colorectal cancer pathogenesis. Using WB and PCR experiments, we found that PSAT1 has a role in regulating EMT development in CRC.In terms of mechanism, we found that PSAT1 affected EMT by Regulating Pl3K/AKT Signaling Pathway. Results: Our investigation revealed a noteworthy down-regulation of PSAT1 expression in CRC specimens. Importantly, this down-regulation exhibited a significant positive correlation with the unfavorable prognosis of patients afflicted with CRC. Functionally, our study showcased that the siRNA-mediated knockdown of PSAT1 markedly enhanced various key aspects of CRC pathogenesis in an in vitro setting. Specifically, this included a substantial promotion of CRC cell migration, invasion, proliferation, and colony formation. Moreover, the silencing of PSAT1 also demonstrated a substantial promotion of the EMT process. Intriguingly, our research unveiled a hitherto unexplored mechanism underlying the regulatory role of PSAT1 in CRC and EMT. We have established, for the first time, that PSAT1 exerts its influence by modulating the activation of the PI3K/AKT Signaling Pathway. This mechanistic insight provides a valuable contribution to the understanding of the molecular underpinnings of CRC progression and EMT induction mediated by PSAT1. Conclusions: In unison, our research findings shed light on the previously uncharted and significant role of the PSAT1/PI3K/AKT axis in the initiation of the EMT process in CRC. Furthermore, our discoveries introduce a novel biomarker with potential implications for the clinical diagnosis and treatment of CRC.

Active Beam Steering Enabled by Photonic-Crystal Surface-Emitting Laser.

Emitting light toward on-demand directions is important for various optoelectronic applications, such as optical communication, displaying, and ranging. However, almost all existing directional emitters are assemblies of passive optical antennae and external light sources, which are usually bulky and fragile and show unendurable loss of light power. Here we theoretically propose and experimentally demonstrate a conceptual design of a directional emitter, by using a single surface-emitting laser source itself to achieve dynamically controlled beam steering. The laser is built on photonic crystals that operate near the band edges in the continuum. By shrinking laser sizes to tens-of-wavelength, the optical modes quantize in three-dimensional momentum space, and each of them directionally radiates toward the far-field. Further utilizing the luminescence spectrum shifting effect under current injection, we consecutively select a sequence of modes into lasing action and show the laser maintaining single-mode operation with line widths at a minimum of 1.8 MHz and an emitting power of ∼10 milliwatts, and we demonstrate fast beam steering across a range of 3.2° × 4° on a time scale of 500 ns. Our work proposes a method for on-chip active beam steering for the development of automotive, industrial, and robotic applications.

Dynamic distribution of gut microbiota in cattle at different breeds and health states.

Weining cattle is a precious species with high tolerance to cold, disease, and stress, and accounts for a large proportion of agricultural economic output in Guizhou, China. However, there are gaps in information about the intestinal flora of Weining cattle. In this study, high-throughput sequencing were employed to analyze the intestinal flora of Weining cattle (WN), Angus cattle (An), and diarrheal Angus cattle (DA), and explore the potential bacteria associated with diarrhea. We collected 18 fecal samples from Weining, Guizhou, including Weining cattle, Healthy Angus, and Diarrheal Angus. The results of intestinal microbiota analysis showed there were no significant differences in intestinal flora diversity and richness among groups (p > 0.05). The abundance of beneficial bacteria (Lachnospiraceae, Rikenellaceae, Coprostanoligenes, and Cyanobacteria) in Weining cattle were significantly higher than in Angus cattle (p < 0.05). The potential pathogens including Anaerosporobacter and Campylobacteria were enriched in the DA group. Furthermore, the abundance of Lachnospiraceae was very high in the WN group (p < 0.05), which might explain why Weining cattle are less prone to diarrhea. This is the first report on the intestinal flora of Weining cattle, furthering understanding of the relationship between intestinal flora and health.

Fiscal decentralization, local government environmental protection preference, and regional green innovation efficiency: evidence from China.

Green technological innovation has gained in importance in regional policy making towards gaining competitive advantage and sustainable development. This paper used the data envelopment analysis method to calculate regional green innovation efficiency in China, and empirically tested the effect of fiscal decentralization through Tobit model. The regression results show that the local governments with higher fiscal autonomy would prefer to strengthen environmental protection; thus, the regional green innovation efficiency was improved. After the guidance of relevant national development strategies, these effects became more apparent. Our research provided theoretical support and practical guidance for promoting regional led green innovation, improving environmental quality, achieving carbon neutrality, and promoting the high-quality and sustainable development.