The impact of city-county merger on firm-level total factor productivity-Evidence from China.

This study examines the potential negative effects of city-county mergers on firm-level total factor productivity (TFP). A theoretical framework is established to explain how city-county mergers could lead to higher institutional and non-institutional costs, thus influencing government decision-making and resource allocation. As a result, firms operating in the economy will absorb these costs and adjust their behavior accordingly. By employing Chinese firm-level data in a difference-in-differences approach, this study finds a statistically significant negative effect of transitioning county-level cities into municipal districts (TCD) on firm-level productivity. Additionally, this study identifies the financial situation of reformed governments and the internal environment of firms as two mechanisms through which the TCD reform influences firm-level productivity.

The Design of a Fiber-Coupling Micro-Lens Array for an M × N Wavelength-Selective Switch.

The M × N port wavelength-selective switch (WSS) is a crucial device used for Reconfigurable Optical Add/Drop Multiplexors and optical switching nodes in optical communication systems. The primary function of an M × N port WSS is to simultaneously transmit and switch multiple input optical signals from input fiber ports to output fiber ports through spatial light coupling. The port array module in a WSS that is responsible for coupling the spatial beam with the fiber determines the important parameters of the M × N port WSS, such as the number of input/output ports and insertion loss. In this paper, VirtualLab Fusion software 2023.1 (Build 1.558), as a powerful physical optics simulation tool, is used to design and optimize a silicon micro-lens array that can achieve the high-precision coupling of a fiber array with a pitch of 1143 µm. Finally, the designed micro-lens is manufactured and experimentally demonstrates its good beam focusing ability with a 3 dB insertion loss. The designed micro-lens array coupling system, which delivers 28 focused spots of approximately 1mm in size (the beam has a 1/e2 diameter) after transmitting a distance of around 300 mm, effectively extends the number of WSS ports. This design method of the micro-lens array significantly amplifies the port count of the M × N port wavelength-selective switch, effectively expanding it to encompass an impressive 28 × 28 ports.

Modified low CSPR Kramer-Kronig receivers based on a signal-signal beat interference estimation.

Due to their simple structures and high robustness to fibre dispersion, single-sideband transmission systems using Kramer-Kronig (KK) receivers are an attractive solution for 80 km data centre interconnects. However, a major problem with KK receivers is that the optimal carrier signal power ratio (CSPR) needs to be large, due to the existence of signal-signal beat interference (SSBI), but this results in low receiver sensitivity. We propose two modified KK receivers that can estimate and eliminate SSBI and allow for signal detection when the CSPR is less than 0 dB. After transmission over an 80 km optical fibre, our modified KK receivers were able to increase the receiver sensitivity by 3 dB compared with a traditional KK receiver while the CSPR was reduced by 6 dB, and improvements of 1.16 and 1.60 dB in the OSNR were achieved with a reduction in the CSPR of 8 dB. Our improved KK receivers can greatly reduce the carrier power and CSPR necessary for the system, and thus reduce the cost of the system transmitter.

Avasimibe Dampens Cholangiocarcinoma Progression by Inhibiting FoxM1-AKR1C1 Signaling.

Avasimibe is a bioavailable acetyl-CoA acetyltransferase (ACAT) inhibitor and shows a good antitumor effect in various human solid tumors, but its therapeutic value in cholangiocarcinoma (CCA) and underlying mechanisms are largely unknown. In the study, we proved that avasimibe retard cell proliferation and tumor growth of CCAs and identified FoxM1/AKR1C1 axis as the potential novel targets of avasimibe. Aldo-keto reductase 1 family member C1 (AKR1C1) is gradually increased along with the disease progression and highly expressed in human CCAs. From survival analysis, AKR1C1 could be a vital predictor of tumor recurrence and prognostic factor. Enforced Forkhead box protein M1 (FoxM1) expression results in the upregulation of AKR1C1, whereas silencing FoxM1 do the opposite. FoxM1 directly binds to promoter of AKR1C1 and triggers its transcription, while FoxM1-binding site mutation decreases AKR1C1 promoter activity. Moreover, over-expressing exogenous FoxM1 reverses the growth retardation of CCA cells induced by avasimibe administration, while silencing AKR1C1 in FoxM1-overexpressing again retard cell growth. Furthermore, FoxM1 expression significantly correlates with the AKR1C1 expression in human CCA specimens. Our study demonstrates a novel positive regulatory between FoxM1 and AKR1C1 contributing cell growth and tumor progression of CCA and avasimibe may be an alternative therapeutic option for CCA by targeting this FoxM1/AKR1C1 signaling pathway.

Identification of Metastasis-Associated MicroRNAs in Metastatic Melanoma by miRNA Expression Profile and Experimental Validation.

It is reported that microRNAs (miRNA) have paramount functions in many cellular biological processes, development, metabolism, differentiation, survival, proliferation, and apoptosis included, some of which are involved in metastasis of tumors, such as melanoma. Here, three metastasis-associated miRNAs, miR-18a-5p (upregulated), miR-155-5p (downregulated), and miR-93-5p (upregulated), were identified from a total of 63 different expression miRNAs (DEMs) in metastatic melanoma compared with primary melanoma. We predicted 262 target genes of miR-18a-5p, 904 miR-155-5p target genes, and 1220 miR-93-5p target genes. They participated in pathways concerning melanoma, such as TNF signaling pathway, pathways in cancer, FoxO signaling pathway, cell cycle, Hippo signaling pathway, and TGF-beta signaling pathway. We identified the top 10 hub nodes whose degrees were higher for each survival-associated miRNA as hub genes through constructing the PPI network. Using the selected miRNA and the hub genes, we constructed the miRNA-hub gene network, and PTEN and CCND1 were found to be regulated by all three miRNAs. Of note, miR-155-5p was obviously downregulated in metastatic melanoma tissues, and miR-18a-5p and miR-93-5p were obviously regulated positively in metastatic melanoma tissues. In validating experiments, miR-155-5p's overexpression inhibited miR-18a-5p's and miR-93-5p's expression, which could all significantly reduce SK-MEL-28 cells' invasive ability. Finally, miR-93-5p and its potential target gene UBC were selected for further validation. We found that miR-93-5p's inhibition could reduce SK-MEL-28 cell's invasive ability through upregulated the expression of UBC, and the anti-invasive effect was reserved by downregulation of UBC. The results show that the selected three metastasis-associated miRNAs participate in the process of melanoma metastasis via regulating their target genes, providing a potential molecular mechanism for this disease.

Predicting gastric cancer outcome from resected lymph node histopathology images using deep learning.

N-staging is a determining factor for prognostic assessment and decision-making for stage-based cancer therapeutic strategies. Visual inspection of whole-slides of intact lymph nodes is currently the main method used by pathologists to calculate the number of metastatic lymph nodes (MLNs). Moreover, even at the same N stage, the outcome of patients varies dramatically. Here, we propose a deep-learning framework for analyzing lymph node whole-slide images (WSIs) to identify lymph nodes and tumor regions, and then to uncover tumor-area-to-MLN-area ratio (T/MLN). After training, our model's tumor detection performance was comparable to that of experienced pathologists and achieved similar performance on two independent gastric cancer validation cohorts. Further, we demonstrate that T/MLN is an interpretable independent prognostic factor. These findings indicate that deep-learning models could assist not only pathologists in detecting lymph nodes with metastases but also oncologists in exploring new prognostic factors, especially those that are difficult to calculate manually.

ACOT4 accumulation via AKT-mediated phosphorylation promotes pancreatic tumourigenesis.

The acyl-CoA thioesterase (ACOT) family catalyses the hydrolysis of acyl-CoA thioesters to their corresponding non-esterified fatty acid and coenzyme A (CoA). Increasing evidence suggests that cancer cells generally have altered lipid metabolism in different aspects. However, the roles of the ACOT family in cancer, especially in pancreatic ductal carcinoma (PDAC), are largely unknown. In the present study, we mined data to determine the clinical significance of all eleven ACOT genes among nine major solid tumour types from TCGA database and found that the expression of ACOT4 in PDAC was negatively correlated with patient survival, establishing ACOT4 as a potential biomarker of PDAC. Depletion of ACOT4 attenuated the proliferation and tumour formation of PDAC cells. Using mass spectrometry, HSPA1A was found to associate with ACOT4. Furthermore, we found that phosphorylation of ACOT4 at S392 by AKT decreased the binding of ACOT4 to HSPA1A, resulting in ACOT4 accumulation. The ACOT4 elevation promotes pancreatic tumourigenesis by producing excessive CoA to support tumour cell metabolism. Thus, our study expands the relationship between AKT signalling and lipid metabolism and establishes a functional role of ACOT4 in PDAC.

Wavelength-Flexible Thulium-Doped Fiber Laser Based on Digital Micromirror Array.

Wavelength-tunable thulium-doped fiber laser is demonstrated employing a digital micromirror device (DMD) in combination with a fixed grating. The diffraction property of four typical models of DMDs and its steering efficiency for the laser system are analyzed based on two-dimensional grating theory. By spatially modulating reflective patterns on a DMD, the stable, fast, and flexible tuning of lasing wavelength from 1930 nm to 2000 nm is achieved with wavelength tuning accuracy of 0.1 nm. The side-mode suppression ratio is larger than 50 dB around the 2 µm band with 3 dB linewidth less than 0.05 nm. The wavelength drift and power fluctuation are lower than 0.05 nm and 0.1 dB within 1 h at the room temperature, respectively.

Programmable Spectral Filter in C-Band Based on Digital Micromirror Device.

Optical filters have been adopted in many applications such as reconfigurable telecommunication switches, tunable lasers and spectral imaging. However, most of commercialized filters based on a micro-electrical-mechanical system (MEMS) only provide a minimum bandwidth of 25 GHz in telecom so far. In this work, the programmable filter based on a digital micromirror device (DMD) experimentally demonstrated a minimum bandwidth of 12.5 GHz in C-band that matched the grid width of the International Telecommunication Union (ITU) G.694.1 standard. It was capable of filtering multiple wavebands simultaneously and flexibly by remotely uploading binary holograms onto the DMD. The number of channels and the center wavelength could be adjusted independently, as well as the channel bandwidth and the output power. The center wavelength tuning resolution of this filter achieved 0.033 nm and the insertion loss was about 10 dB across the entire C-band. Since the DMD had a high power handling capability (25 KW/cm²) of around 200 times that of the liquid crystal on silicon (LCoS) chip, the DMD-based filters are expected to be applied in high power situations.

Tunable Fiber Laser with High Tuning Resolution in C-band Based on Echelle Grating and DMD Chip.

The tunable fiber laser with high tuning resolution in the C-band is proposed and demonstrated based on a digital micromirror device (DMD) chip and an echelle grating. The laser employs a DMD as a programmable wavelength filter and an echelle grating with high-resolution features to design a cross-dispersion optical path to achieve high-precision tuning. Experimental results show that wavelength channels with 3 dB-linewidth less than 0.02 nm can be tuned flexibly in the C-band and the wavelength tuning resolution is as small as 0.036 nm. The output power fluctuation is better than 0.07 dB, and the wavelength shift is below 0.013 nm in 1 h at room temperature.

Overexpression of metabolic markers HK1 and PKM2 contributes to lymphatic metastasis and adverse prognosis in Chinese gastric cancer.

Hexokinase 1 (HK1) and pyruvate kinase M2 (PKM2) are two key regulators in glycosis and oncogenic markers in cancers. In the present study, we investigated the expression profile by Western blotting and immunohistochemistry and determined their prognostic values in the gastric cancer. Expression of HK1 and PKM2 was remarkably increased in gastric cancer tissues and was significantly associated lymphatic metastasis and advanced TNM staging. In the COX regression model, HK1 and TNM stage were analyzed as adverse prognostic indicators in gastric cancer. Furthermore, patients with HK1 expression showed remarkable shorter survival duration in both lymphatic metastasis cohort and advanced staging cohort. Our results suggest that overexpression of PKM2 and HK1, especially the latter, significantly associates with lymphatic metastasis, advanced clinical staging and unfavorable prognosis in gastric cancer.

Metformin potentiates rapamycin and cisplatin in gastric cancer in mice.

Here we showed that pAMPKα and PTEN were down-regulated and p-mTOR, p-S6, p-4EBP1, MMP7, and DCN1 were up-regulated in human gastric cancer tissue samples as compared to that in the noncancerous tissues. Metformin inhibited tumor growth in mice. Also it enhanced cisplatin- or rapamycin-induced reduction of tumor growth as compared with treatment of either drug alone. In addition to activation of AMPK and suppression of the mTOR pathway, a series of increased and decreased genes expression were induced by metformin, including PTEN, MMP7, and FN1. We suggest that metformin could potentially be used for the treatment of gastric cancer especially in combination with cisplatin or rapamycin.

Genetic association between leptin-2548G/A polymorphism and risk of cancer: a meta analysis.

OBJECTIVE: Abundance of evidence implicated that leptin may play a decisive role in cancer occurrence, but the reported results varied across the individually published studies. The objective of this study is to access to what extent the extensively studied -2548G/A polymorphism of LEP gene acts on the onset of multiple cancers. METHODS: Eligible studies included in this meta-analysis were identified electronically in PubMed and Embase, and manually in relevant literature. Crude odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated to estimate the risk of cancer associated with the -2548G/A polymorphism. RESULTS: 12 association studies with a total of 5,618 cancer cases and 6,509 healthy controls were pooled into this meta-analysis. The results revealed that compared with the G allele, the A allele was associated with modestly increased risk of overall cancer (OR, 1.21; 95% CI, 1.02-1.44). Following further stratified analyses, a borderline association was indicated in prostate cancer (OR, 1.18; 95% CI, 1.00-1.39), breast cancer (OR, 1.11; 95% CI, 1.00-1.22) and Caucasians (OR, 1.19; 95% CI, 1.00-1.41). CONCLUSIONS: This meta-analysis reveals that the A allele of -2548G/A polymorphism may be a determinant of cancer development.

Differential expression of ANXA1 in benign human gastrointestinal tissues and cancers.

BACKGROUND: Annexin-1 contributes to the pathological consequence and sequelae of most serious human diseases including cardiovascular disease and cancer. Although diverse roles in carcinogenesis have been postulated, its role in human gastrointestinal cancers still remains controversial. METHODS: The mRNA and protein expression profiles of ANXA1 were studied in human esophageal, gastric, pancreatic, colorectal, liver, and bile duct cancers using Real-Time PCR, western blotting, and immunohistochemistry. Gain/loss-of-function by pcDNA3.1-ANXA1 and ANXA1-shRNA was performed in gastric cancer cells. RESULTS: ANXA1 was widely expressed in adult gastrointestinal tissue. All methods showed that ANXA1 was down-regulated in esophageal, gastric, and bile duct cancers, but up-regulated in pancreatic cancer. Forced ANXA1 expression in gastric cancer cells leads to cell growth inhibition and concomitantly modulates COX-2 expression. We confirm loss of ANXA1 and overexpression of COX-2 in clinical gastric cancer, suggesting that the anti-proliferative function of ANXA1 against COX-2 production might be lost. CONCLUSIONS: ANXA1 expression is "tumor-specific" and might play a multifaceted role in cancer development and progression. ANXA1 was widely expressed in normal gastrointestinal epithelium, suggesting its role in the maintenance of cellular boundaries. Furthermore, ANXA1 regulates GC cell viability via the COX-2 pathway.

Reduced expression of EphB2 is significantly associated with nodal metastasis in Chinese patients with gastric cancer.

AIMS: EphB2 is a member of the Eph receptor tyrosine kinase family that has been involved in the regulation of cytoskeleton organization and cell migration in various cell types. Its role and regulation in carcinogenesis is controversial, especially in gastric cancer. We detected EphB2 expression and determined its clinical significance and explored its underlying molecular mechanism in gastric cancers. METHODS: Tissue microarray blocks containing primary gastric cancer, lymph node metastases, and adjacent normal mucosa specimens obtained from 337 Chinese patients were constructed. Expression of EphB2 in these specimens was analyzed using immunohistochemistry. Mutation analysis at the A9 tract in exon 17 and loss of heterozygosity analysis at the EphB2 gene locus were carried out in 13 sporadic EphB2-negative gastric cancers. RESULTS: Complete loss of EphB2 expression was observed in 177 (52.5%) of the 337 primary tumor and 41 (82%) of the 50 nodal metastases. Loss of EphB2 expression was significantly associated with advanced T stage, nodal metastasis, advanced disease stage, and poor histological differentiation. Loss of EphB2 expression correlated significantly with poor survival rates in both univariate and multivariate analysis. No frameshift mutation, but a higher frequency of allelic loss, was found in EphB2-negative primary and metastatic tumor samples. CONCLUSIONS: Frequent deletion and decreased expression of EphB2 protein suggested it as a negative biomarker for gastric carcinogenesis and a potential predictor of the outcome of patients with gastric cancer.