Polarization-insensitive and high-efficiency edge coupler for thin-film lithium niobate.

In this Letter, we propose and demonstrate a fiber-to-chip edge coupler (EC) on an x-cut thin film lithium niobate (TFLN) for polarization-insensitive (PI) coupling. The EC consists of three width-tapered full-etched waveguides with silica cladding and matches well with a single-mode fiber (SMF). The measured results show that the minimum coupling losses for TE0/TM0 modes remain to be 0.9 dB/1.1 dB per facet, and the polarization dependent loss (PDL) is <0.5 dB over the wavelength range from 1260 to 1340 nm. Moreover, the EC features large misalignment tolerance of ±2 µm in the Z direction and ±1.5 µm in the X direction for both polarizations for a 1 dB penalty. To the best of our knowledge, this is the first realized O-band edge coupler on TFLN with SMF. The proposed device shows promising potential for integration into TFLN polarization diversity devices.

High performance polarizer on thin-film lithium niobate with width-tapered Euler bending.

In this Letter, we propose and demonstrate an integrated polarizer on thin film lithium niobate (TFLN). The polarizer consists of a width-tapered 180° Euler bending waveguide featuring thin thickness and bilevel mode convertors with silica cladding. Notably, the TE0 mode is efficiently confined in the waveguide, while the TM0 mode confronts significant bending losses. The measurements reveal that the excess loss remains below 1.5 dB, and the extinction ratio surpasses 19 dB within a working bandwidth spanning from 1480 to 1578 nm. The proposed polarizer holds considerable promise for enhancing polarization handling within TFLN photonic circuits.

Demonstration of high-speed thin-film lithium-niobate-on-insulator optical modulators at the 2-µm wavelength.

Optical communication wavelength is being extended from the near-infrared band of 1.31/1.55 µm to the mid-infrared band of 2 µm or beyond for satisfying the increasing demands for high-capacity long-distance data transmissions. An efficient electro-optic (EO) modulator working at 2 µm is highly desired as one of the indispensable elements for optical systems. Lithium niobate (LiNbO3) with a large second-order nonlinear coefficient is widely used in various EO modulators. Here, we experimentally demonstrate the first Mach-Zehnder EO modulator working at 2 µm based on the emerging thin-film LiNbO3 platform. The demonstrated device exhibits a voltage-length product of 3.67 V·cm and a 3-dB-bandwidth of >22 GHz which is limited by the 18 GHz response bandwidth of the photodetector available in the lab. Open eye-diagrams of the 25 Gb/s on-off keying (OOK) signals modulated by the fabricated Mach-Zehnder EO modulator is also measured experimentally with a SNR of about 14 dB.

Mach-Zehnder silicon-photonic switch with low random phase errors.

A Mach-Zehnder silicon photonic switch with low random phase errors is proposed and demonstrated for the first time, to the best of our knowledge, by incorporating judiciously widened and shortened phase shifter waveguides. With a 180 nm complementary metal-oxide-semiconductor (CMOS) foundry process, more than one hundred 2×2 thermo-optic Mach-Zehnder switches (MZSs) with varied phase shifter widths have been designed, fabricated, and characterized on 14 silicon chips. The mean and standard deviation of the random phase errors of the MZSs with phase shifters widened to 2 µm are less than a third of those of the conventional design with 0.45-µm-wide single-mode phase shifters. This validates the improved fabrication tolerance and results in considerable reduction of the power consumption for the phase error compensation. Such elegant methodology paves the way to further scaling up N×N silicon thermo-optic switches and can be generalized for other phase-sensitive integrated photonic devices as well.

Regulation of YAP translocation by myeloid Pten deficiency alleviates acute lung injury via inhibition of oxidative stress and inflammation.

BACKGROUND: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is intricately involved in modulating the inflammatory response in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Nevertheless, the myeloid PTEN governing Hippo-YAP pathway mediated oxidative stress and inflammation in lipopolysaccharide (LPS)-induced ALI remains to be elucidate. METHODS: The floxed Pten (PtenFL/FL) and myeloid-specific Pten knockout (PtenM-KO) mice were intratracheal instill LPS (5 mg/kg) to establish ALI, then Yap siRNA mix with the mannose-conjugated polymers was used to knockdown endogenous macrophage YAP in some PtenM-KO mice before LPS challenged. The bone marrow-derived macrophages (BMMs) from PtenFL/FL and PtenM-KO mice were obtained, and BMMs were transfected with CRISPR/Cas9-mediated glycogen synthase kinase 3 Beta (GSK3ß) knockout (KO) or Yes-associated protein (YAP) KO vector subjected to LPS (100 ng/ml) challenged or then cocultured with MLE12 cells. RESULTS: Here, our findings demonstrate that myeloid-specific PTEN deficiency exerts a protective against LPS-induced oxidative stress and inflammation dysregulated in ALI model. Moreover, ablation of the PTEN-YAP axis in macrophages results in reduced nuclear factor-E2-related factor-2 (NRF2) expression, a decrease in antioxidant gene expression, augmented levels of free radicals, lipid and protein peroxidation, heightened generation of pro-inflammatory cytokines, ultimately leading to increased apoptosis in MLE12 cells. Mechanistically, it is noteworthy that the deletion of myeloid PTEN promotes YAP translocation and regulates NRF2 expression, alleviating LPS-induced ALI via the inhibition of GSK3ß and MST1 binding. CONCLUSIONS: Our study underscores the crucial role of the myeloid PTEN-YAP-NRF2 axis in governing oxidative stress and inflammation dysregulated in ALI, indicating its potential as a therapeutic target for ALI.

Increased expression of Rho-associated protein kinase 2 confers astroglial Stat3 pathway activation during epileptogenesis.

Patients with TLE are prone to tolerance to antiepileptic drugs. Based on the perspective of molecular targets for drug resistance, it is necessary to explore effective drug resistant genes and signaling pathways for the treatment of TLE. We performed gene expression profiles in hippocampus of patients with drug-resistant TLE and identified ROCK2 as one of the 20 most significantly increased genes in hippocampus. In vitro and in vivo experiments were performed to identify the potential role of ROCK2 in epileptogenesis. In addition, the activity of Stat3 pathway was tested in rat hippocampal tissues and primary cultured astrocytes. The expression levels of ROCK2 in the hippocampus of TLE patients were significantly increased compared with the control group, which was due to the hypomethylation of ROCK2 promoter. Fasudil, a specific Rho-kinase inhibitor, alleviated epileptic seizures in the pilocarpine rat model of TLE. Furthermore, ROCK2 activated the Stat3 pathway in pilocarpine-treated epilepsy rats, and the spearman correlation method confirmed that ROCK2 is associated with Stat3 activation in TLE patients. In addition, ROCK2 was predominantly expressed in astrocytes during epileptogenesis, and induced epileptogenesis by activating astrocyte cell cycle progression via Stat3 pathway. The overexpressed ROCK2 plays an important role in the pathogenesis of drug-resistant epilepsy. ROCK2 accelerates astrocytes cell cycle progression via the activation of Stat3 pathway likely provides the key to explaining the process of epileptogenesis.

Case Report: Multiple Seizures After a Diphenoxylate-Atropine Overdose in a Small Child.

Poisoning is a type of accidental injury and it is considered a major public health problem worldwide. Oral drug poisoning in children is an important cause of accidental injury and even death. It is a common critical emergency in the field of pediatrics. Once a child unintentionally takes an overdose, regardless of whether it caused poisoning or not, they should be admitted to the hospital for emergency treatment. Acute poisoning in children most frequently occurs through the digestive tract. Drug poisoning can happen in children of all ages. In children younger than 1 year, drug poisoning is mostly caused by the parents during feeding, while in children aged 1-3 years, it predominantly occurs as a result of an accident. A case of diagnosis and treatment of a child with diphenoxylate-atropine poisoning is reported herein. The early manifestation of this child was acute toxic encephalopathy with clinical manifestations of a coma, convulsions, and respiratory depression. A brain MRI showed extensive damage to the bilateral caudate nucleus, lenticular nucleus, parietal lobe, precuneus lobe, and occipital lobe. Accidental administration of a large dose of diphenoxylate results in severe clinical symptoms and can cause obvious diffuse brain damage.

[Two novel RUNX2 gene mutations in two Chinese families with cleidocranial dysplasia].

OBJECTIVE: To identify the RUNX2 gene mutation in two unrelated Chinese families with cleidocranial dysplasia (CCD), and to assess the feasibility of gene diagnosis for patients with CCD. METHODS: Genomic DNA was isolated from peripheral blood samples of 4 patients and 4 healthy members in the two pedigrees as well as 102 unrelated healthy controls. All 7 coding exons and their flanking intronic sequences of the RUNX2 gene were amplified by PCR, then the PCR products were sequenced bi-directionally. The sequencing results were compared with normal sequences in GenBank to identify the mutation. The mutation was confirmed by RFLP with restriction endonuclease. RESULTS: In one family, a novel heterozygous missense mutation c.346T to A (W116R) in exon 1 of the RUNX2 gene was detected in the two affected individuals, and the mutation was further confirmed with Bsr I restriction endonuclease digestion. In the other family, a novel nonsense mutation c.610A TO T (K204X) was identified in the two patients. No above sequence change was found in the 102 healthy controls. CONCLUSION: Two novel RUNX2 mutations were found in two unrelated Chinese families with cleidocranial dysplasia. The identification of these mutations further extended the mutation spectrum of RUNX2 gene and will facilitate prenatal diagnosis and gene diagnosis of CCD.

Fatty Acid Metabolism is Associated With Disease Severity After H7N9 Infection.

BACKGROUND: Human infections with the H7N9 virus could lead to lung damage and even multiple organ failure, which is closely associated with a high mortality rate. However, the metabolic basis of such systemic alterations remains unknown. METHODS: This study included hospitalized patients (n = 4) with laboratory-confirmed H7N9 infection, healthy controls (n = 9), and two disease control groups comprising patients with pneumonia (n = 9) and patients with pneumonia who received steroid treatment (n = 10). One H7N9-infected patient underwent lung biopsy for histopathological analysis and expression analysis of genes associated with lung homeostasis. H7N9-induced systemic alterations were investigated using metabolomic analysis of sera collected from the four patients by using ultra-performance liquid chromatography-mass spectrometry. Chest digital radiography and laboratory tests were also conducted. FINDINGS: Two of the four patients did not survive the clinical treatments with antiviral medication, steroids, and oxygen therapy. Biopsy revealed disrupted expression of genes associated with lung epithelial integrity. Histopathological analysis demonstrated severe lung inflammation after H7N9 infection. Metabolomic analysis indicated that fatty acid metabolism may be inhibited during H7N9 infection. Serum levels of palmitic acid, erucic acid, and phytal may negatively correlate with the extent of lung inflammation after H7N9 infection. The changes in fatty acid levels may not be due to steroid treatment or pneumonia. INTERPRETATION: Altered structural and secretory properties of the lung epithelium may be associated with the severity of H7N9-infection-induced lung disease. Moreover, fatty acid metabolism level may predict a fatal outcome after H7N9 virus infection.

Decreased astroglial monocarboxylate transporter 4 expression in temporal lobe epilepsy.

Efflux of monocaroxylates like lactate, pyruvate, and ketone bodies from astrocytes through monocarboxylate transporter 4 (MCT4) supplies the local neuron population with metabolic intermediates to meet energy requirements under conditions of increased demand. Disruption of this astroglial-neuron metabolic coupling pathway may contribute to epileptogenesis. We measured MCT4 expression in temporal lobe epileptic foci excised from patients with intractable epilepsy and in rats injected with pilocarpine, an animal model of temporal lobe epilepsy (TLE). Cortical MCT4 expression levels were significantly lower in TLE patients compared with controls, due at least partially to MCT4 promoter methylation. Expression of MCT4 also decreased progressively in pilocarpine-treated rats from 12 h to 14 days post-administration. Underexpression of MCT4 in cultured astrocytes induced by a short hairpin RNA promoted apoptosis. Knockdown of astrocyte MCT4 also suppressed excitatory amino acid transporter 1 (EAAT1) expression. Reduced MCT4 and EAAT1 expression by astrocytes may lead to neuronal hyperexcitability and epileptogenesis in the temporal lobe by reducing the supply of metabolic intermediates and by allowing accumulation of extracellular glutamate.