[Clinical presentation of acute primary angle-closure glaucoma during the 2019-nCoV epidemic of Omicron variants: a single-center retrospective study].

Objective: To investigate the clinical presentation pattern of acute primary angle-closure glaucoma (PACG) during the 2019 novel coronavirus (2019-nCoV) pandemic over the past three years, and its relationship with 2019-nCoV infections of Omicron variants in Guangdong province. Methods: Ecological study.Patients who were newly diagnosed with acute PACG from February 2020 to January 2023 at the Zhongshan Ophthalmic Center of Sun Yat-sen University were included in the study, and their basic information was collected. Patients were divided into the 2020 group (diagnosed between February 1st, 2020 and January 31st 2021), the 2021 group (diagnosed between February 1st, 2021 and January 31st 2022), and the 2022 group (diagnosed between February 1st, 2022 and January 31st 2023). The clinical presentation pattern of newly diagnosed acute PACG was observed and compared between groups. The daily number of newly diagnosed 2019-nCoV infections in Guangdong province was obtained from the Chinese Center for Disease Control and Prevention. The correlation between the daily number of newly diagnosed acute PACG and that of newly diagnosed 2019-nCoV infections during the epidemic period of Omicron variants between December 2022 and January 2023 was assessed. Results: The study included 1 048 patients with newly diagnosed acute PACG, with 235 for the 2020 group, 274 for the 2021 group, and 539 for the 2022 group. Our results showed that the average weekly number of newly diagnosed acute PACG patients in 2022 [8 (5, 11)] was significantly larger than that in 2020 (4.52±1.95, P<0.05) and 2021 (5.27±2.76, P<0.05). The average weekly number increased to 22.11±20.84 between December 2022 and January 2023. The total number of newly diagnosed acute PACG patients during this period was 199, which was 36.9% (199/539) of the total number of the same year and was 6.63 and 6.42 times as many as that in the same period (December and January) of 2020 and 2021. The proportion of patients with bilateral eye involvement during this period in 2022 was significantly higher than that in 2020 and 2021 (P<0.05). Further analysis found that 88.6% (109/123) of cases had a history of 2019-nCoV infection 2 (0, 3) days before the onset of acute PACG symptoms in average. The estimated daily number of acute PACG onset increased rapidly, peaked on December 23th, 2022, and then dropped gradually. This trend was similar to that of the daily number of new 2019-nCoV infections in Guangdong province. Changes of the daily number of new 2019-nCoV infections in Guangdong province had a positive correlation with the estimated daily number of acute PACG onset (r=0.84, P<0.001). Conclusion: A dramatic increase in the clinical presentation of acute PACG was observed at Zhongshan Ophthalmic Center between December 2022 and January 2023, which was the epidemic period of Omicron variants. There is a correlation between the trend of the estimated daily number of acute PACG onset and that of new 2019-nCoV infections of Omicron variants in Guangdong province, but the exact reason remains to be further studied. (This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on August 31, 2023).

p53 directly regulates αA- and ßA3/A1-crystallin genes to modulate lens differentiation.

It is well established that the tumor suppressor p53 plays major roles in regulating apoptosis and cell cycle progression. In addition, recent studies have demonstrated that p53 is actively involved in regulating cell differentiation in muscle, the circulatory system and various carcinoma tissues. We have recently shown that p53 also controls lens differentiation. Regarding the mechanism, we reveal that p53 directly regulates c-Maf and Prox1, two important transcription factors to control cell differentiation in the ocular lens. In the present study, we present further evidence to show that p53 can regulate lens differentiation by controlling expression of the differentiation genes coding for the lens crystallins. First, the αA and ßA3/A1 gene promoters or introns all contain putative p53 binding sites. Second, gel mobility shifting assays revealed that the p53 protein in nuclear extracts from lens epithelial cells directly binds to the p53 binding sites found in these crystallin gene promoters or introns. Third, exogenous wild type p53 induces dose-dependent expression of the luciferase reporter gene driven by different crystallin gene promoters and the exogenous dominant negative mutant p53 causes dose-dependent inhibition of the same crystallin genes. Fourth, ChIP assays revealed that p53 binds to crystallin gene promoters in vivo. Finally, in the p53 knockout mouse lenses, expression levels of various crystallins were found down-regulated in comparison with those from the wild type mouse lenses. Together, our results reveal that p53 directly regulates expression of different sets of genes to control lens differentiation.

C-Jun terminal kinases play an important role in regulating embryonic survival and eye development in vertebrates.

The c-Jun N-terminal kinases (JNKs) constitute one of the three major types of mitogen-activated protein kinases. Previous studies showed that JNK mediates multiple signaling transduction pathways implicated in cell proliferation, differentiation, inflammation, stress response and apoptosis in mammals. In the present study, we use goldfish as a model system and demonstrate that JNK kinases are necessary to promote embryonic survival and regulate eye development in vertebrates. During goldfish development, JNK1 and JNK2 are expressed at every stage from cleavage to hatching larvae. JNK3 is turned on at the gastrulation stage and then expressed at similar level to that of JNK2. JNK1 activity remains slightly fluctuated during different developmental stages. Inhibition of JNK activity caused massive apoptosis of blastula cells and significant death of goldfish embryos, which are associated with altered expression of the anti-apoptotic regulator, Mcl-1 and the proapoptotic regulator, Bak. These results provide novel information regarding the mechanisms by which JNKs promote embryonic survival. In addition, the embryos that survived inhibition of JNK activity displayed severe phenotype in the eye with clear microphthalmia and lens coloboma. To confirm that the observed phenotype is derived from JNK activity deficiency, we expressed JNK dominant negative mutant (DNM-JNK) in goldfish. Expression of DNM-JNK also caused similar phenotypes with altered expression of pax-6, Sox-2 and ß-crystallin. Together, our results demonstrate that JNKs play important roles in promoting survival of vertebrate embryos and regulating development of vertebrate eye.

Protein serine/threonine phosphotase-1 is essential in governing normal development of vertebrate eye.

Protein serine/threonine phosphatase-1 (PP-1) is one of the key enzymes responsible for dephosphorylation in vertebrates. Protein dephosphorylation via PP-1 is implicated in many different biological processes including gene expression, cell cycle control, transformation, neuronal transmission, apoptosis, autophage and senescence. However, whether PP-1 directly controls animal development remains to be investigated. Here, we present direct evidence to show that PP-1 plays an essential role in regulating eye development of vertebrates. Using goldfish as a model system, we have shown the following novel results. First, inhibition of PP-1 activity leads to death of a majority of the treated embryos, and the survived embryos displayed severe phenotype in the eye. Second, knockdown of each catalytic subunit of PP-1 with morpholino oligomers leads to partial (PP-lα knockdown) or complete (PP-lß or PP-lγ knockdown) death of the injected embryos. The survived embryos from PP-1α knockdown displayed clear retardation in lens differentiation. Finally, overexpression of each subunit of PP-1 also causes death of majority of the injected embryos and leads to abnormal development of goldfish eye. Mechanistically, Pax-6 is one of the major downstream targets mediating the effects of PP-1 function since the eye phenotype in Pax-6 knockdown fish is similar to that derived from overexpression of PP-1. Together, our results for the first time provide direct evidence that protein phosphatase-1 plays a key role in governing normal eye formation during goldfish development.

The tumor suppressor p53 regulates c-Maf and Prox-1 to control lens differentiation.

The tumor suppressor p53 plays a key role in regulating apoptosis and cell cycle progression. In addition, p53 is implicated in control of cell differentiation in muscle, the circulatory system, ocular lens and various carcinoma tissues. However, the mechanisms by which p53 controls cell differentiation are not fully understood. Here we present evidence that p53 directly regulates c-Maf and Prox1, two important transcription factors controlling differentiation in the ocular lens. First, human and murine c-Maf and Prox1 gene promoters contain authentic p53 DNA binding sites. Second, p53 directly binds to the p53 binding sites found in the promoter regions. Third, exogenous p53 induces dose-dependent expression of the luciferase report gene driven by both c-Maf and Prox1 promoters, and p53 binds to both promoters in the ChIP assays. Fourth, in the in vitro differentiation model, knockdown of p53 significantly inhibits lens differentiation which is associated with downregulated expression of c-Maf and Prox1. Finally, in p53 knockout mice, the expression of c-Maf and Prox1 are significantly altered. Together, our results reveal that p53 regulates lens differentiation through modulation of two important transcription factors, c-Maf and Prox1, and through them p53 thus controls expression of various differentiation-related downstream crystallin genes.

Dependences of photoluminescence from P-implanted epitaxial Ge.

A systematic investigation has been carried out to study the influence of various annealings and implantations on the photoluminescence (PL) properties of phosphorus (P)-implanted Ge epitaxial films on Si substrate. For un-capped Ge samples, rapid thermal annealing (RTA) at 700 °C for 300 seconds yields the strongest PL emission peaked at 1550 nm. The influence of employing various capping layers (i.e., SiO(2), Si(3)N(4), and α-Si ) on the PL properties has been investigated. The capping layers are found to effectively decrease the dopant loss, leading to a significant PL enhancement. Si(3)N(4) is found to be the most efficient capping layer to prevent dopant out-diffusion and thus lead to strongest PL. Furthermore, it has been found that capping layers not only enhance the PL intensities but also make PL emission peak red- and blue- shift, depending on the stress type of the capping films. The effect of implantation dose on the PL has been also investigated.

A randomized non-inferiority study comparing the addition of exenatide twice daily to sitagliptin or switching from sitagliptin to exenatide twice daily in patients with type 2 diabetes experiencing inadequate glycaemic control on metformin and sitagliptin.

AIMS: To test the hypothesis that glycaemic control achieved when switching sitagliptin to exenatide twice daily plus metformin is non-inferior to adding exenatide twice daily to sitagliptin and metformin. METHODS: Patients with Type 2 diabetes inadequately controlled with sitagliptin plus metformin were randomly assigned to 20 weeks of treatment with twice-daily exenatide plus placebo and metformin (SWITCH, n = 127) or twice-daily exenatide plus sitagliptin and metformin (ADD, n = 128). RESULTS: Non-inferiority (0.4% margin) of SWITCH to ADD treatment, measured by change in HbA(1c) from baseline to week 20, was not shown {between-treatment difference in least-squares mean [95% CI 3 mmol/mol (0.30%)] [0.8-5.8 (0.07-0.53)]}. A greater reduction (P = 0.012) in HbA(1c) [least-squares mean (se)] was experienced by patients in the ADD group {-7 mmol/mol [-0.68%] [0.9 (0.08)]}, compared with those in the SWITCH group {-4 mmol/mol [-0.38%] [1.0 (0.09)]} and a greater proportion (P = 0.027) of patients in the ADD group (41.7%) reached < 7.0% (< 53 mmol/mol) HbA(1c) target, compared with those in the SWITCH group (26.6%) by week 20. Patients in the ADD group experienced greater fasting serum glucose (P = 0.038) and daily mean postprandial self-monitored blood glucose (P = 0.048) reductions, compared with patients in the SWITCH group, by week 20. Patients in both groups experienced a lower incidence of nausea and vomiting compared with previous exenatide studies. CONCLUSIONS: Non-inferiority of SWITCH to ADD treatment was not supported by the results of this study. In patients with Type 2 diabetes inadequately controlled with sitagliptin plus metformin, adding exenatide provided better glycaemic control than switching to exenatide. These results are consistent with the clinical approach that adding is better than switching to another oral anti-hyperglycaemic medication.

Thermo-optical tunable planar ridge microdisk resonator in silicon-on-insulator.

In this work, we design and demonstrate planar ridge microdisk resonators in silicon-on-insulator, which assemble the advantages of microring and microdisk resonators. The dependences of resonator optical modes on the slab thickness and the waveguide-to-resonator coupling gap are investigated. The highest Q-factor obtained is ~4 × 10(5). Using the thermo-optical effect, we attain a resonance wavelength tuning efficiency of ~66.5 pm/mW. We also compare the transmission spectra measured by using wavelength-scanning method and voltage-scanning method and show potential application for the adopted voltage-scanning method.

Laterally-current-injected light-emitting diodes based on nanocrystalline-Si/SiO2 superlattice.

Laterally electrically-pumped Si light-emitting diodes (LEDs) based on truncated nanocrystalline-Si (nc-Si)/SiO2 quantum wells are fabricated with complementary-metal-semiconductor-oxide (CMOS) process. Visible electroluminescence (EL) can be observed under a reverse bias larger than ~6 V. The light emission would probably originate from the spontaneous hot-carrier relaxations within the conduction and the valance bands when the device is sufficiently reverse-biased. The EL spectral profile is found to be modulated by varying structure parameters of the interdigitated finger electrodes. Up to ~20 times EL intensity enhancement is achieved as compared to vertical-current-injection LED prepared using the same material system. Based on the lateral-current-injection scheme, a Si/SiO2 MQW LED with Fabry-Perot (FP) microcavity and an on-chip waveguided LED that emits at 1.55-µm are proposed.

Evolution of modes in a metal-coated nano-fiber.

We report on the evolution of modes in cylindrical metal/dielectric systems. The transition between surface plasmon polaritons and localized modes is documented in terms of the real and imaginary parts of the effective refractive index as a function of geometric and optical parameters. We show the evolution process of SPP and localized modes. New phenomena of coupling between SPP and core-like modes, and of mode gap and super-long surface plasmon polaritons are found and discussed. We conclude that both superluminal light and slow light can be solutions of metallically coated dielectric fibers.

Ultra-high order ring resonator system with sharp transmission peaks.

We propose a relay ring resonator structure which comprises multiple cascaded microring resonators, in which the drop waveguide of a microring resonator is also the input waveguide of the subsequent microring resonator, and so forth. Thus, the transmission response of the relay ring resonator structure has sharp peaks, high out-of-band rejection ratios, and long group delays. A relay ring resonator structure comprising 90 microrings is fabricated on silicon nitride wire waveguides. The simulation and experimental results are in good agreement.

Propagation losses in undoped and n-doped polycrystalline silicon wire waveguides.

Polycrystalline silicon (polySi) wire waveguides with width ranging from 200 to 500 nm are fabricated by solid-phase crystallization (SPC) of deposited amorphous silicon (a-Si) on SiO(2) at a maximum temperature of 1000 degrees C. The propagation loss at 1550 nm decreases from 13.0 to 9.8 dB/cm with the waveguide width shrinking from 500 to 300 nm while the 200-nm-wide waveguides exhibit quite large loss (>70 dB/cm) mainly due to the relatively rough sidewall of waveguides induced by the polySi dry etch. By modifying the process sequence, i.e., first patterning the a-Si layer into waveguides by dry etch and then SPC, the sidewall roughness is significantly improved but the polySi crystallinity is degraded, leading to 13.9 dB/cm loss in the 200-nm-wide waveguides while larger losses in the wider waveguides. Phosphorus implantation causes an additional loss in the polySi waveguides. The doping-induced optical loss increases relatively slowly with the phosphorus concentration increasing up to 1 x 10(18) cm(-3), whereas the 5 x 10(18) cm(-3) doped waveguides exhibit large loss due to the dominant free carrier absorption. For all undoped polySi waveguides, further 1-2 dB/cm loss reduction is obtained by a standard forming gas (10%H(2) + 90%N(2)) annealing owing to the hydrogen passivation of Si dangling bonds present in polySi waveguides, achieving the lowest loss of 7.9 dB/cm in the 300-nm-wide polySi waveguides. However, for the phosphorus doped polySi waveguides, the propagation loss is slightly increased by the forming gas annealing.

Observation of zeroth-order band gaps in negative-refraction photonic crystal superlattices at near-infrared frequencies.

We present the first observations of zero-n[over ] band gaps in photonic crystal superlattices consisting of alternating stacks of negative-index photonic crystals and positive-index dielectric materials in the near-infrared range. Guided by ab initio three-dimensional numerical simulations, the fabricated nanostructured superlattices demonstrate the presence of zeroth-order gaps in remarkable agreement with theoretical predictions across a range of different superlattice periods and unit cell variations. These volume-averaged zero-index superlattice structures present a new type of photonic band gap, with the potential for complete wave front control for arbitrary phase delay lines and open cavity resonances.

Improving coupling efficiency of fiber-waveguide coupling with a double-tip coupler.

A double-tip coupler that comprises two inversely and laterally tapered waveguides is experimentally demonstrated for efficient light coupling between a fiber and a sub-micron silicon nitride waveguide. The coupling efficiency of the fabricated double-tip coupler can be improved by as much as over 2 dB per coupling facet, compared with that of a single-tip one with the same tip width of 180 nm. The effect of the gap width of the double tips on the coupling efficiency is studied both in experiment and simulation.

Low propagation loss SiN optical waveguide prepared by optimal low-hydrogen module.

We investigated low-hydrogen SiN films prepared by a low temperature (350 degrees C) PECVD method. The impact of SiH(4)/N(2) flow ratio and radio frequency power on the hydrogen content in the SiN films was studied. In this work, we demonstrated a low-loss sub-micron SiN waveguide by using the corresponding optimal SiN films. The propagation loss was found to be as low as -2.1+/-0.2 dB/cm at 1550 nm with waveguide cross-section of 700 nm x 400 nm. The results suggest that the SiN films grown by PECVD with low hydrogen can be used in photonics integrated circuits for new generation communications applications.

Cascade wide-angle Y-junction 1 x 16 optical power splitter based on silicon wire waveguides on silicon-on-insulator.

A 1 x 16 optical power splitter with wide splitting angle, uniform outputs, and low excess loss is demonstrated. The 1 x 16 splitter comprising cascaded 1 x 2 splitters with arc-shaped branching waveguides is fabricated on the silicon-on-insulator (SOI) substrate. The gap between the branching waveguides is widened in a short propagation length such that influences of etch residues and air voids in the gap on the optical power uniformity are reduced significantly. The measured power uniformity of the 1 x 16 splitter is better than 0.3 dB at wavelength of 1550 nm.

Effective thermo-optical enhanced cross-ring resonator MZI interleavers on SOI.

A cross-ring (CR-) Mach-Zehnder interferometer (MZI) interleaver structure has been proposed and fabricated. It uses an '8' shaped cross-ring resonator to replace the conventional circular ring resonator. Thus, the new structure can have the function of add-signal. Furthermore, a thermo-optical fine tuning has been applied, which improves the crosstalk performance from approximately -10 dB to approximately -20 dB with 9 V applied on the heater of the 3-dB directional coupler.

Fast and low power Michelson interferometer thermo-optical switch on SOI.

We designed and fabricated silicon-on-insulator based Michelson interferometer (MI) thermo-optical switches with deep etched trenches for heat-isolation. Switch power was reduced approximately 20% for the switch with deep etched trenches, and the MI saved approximately 50% power than that of the Mach-Zehnder interferometer. 10.6 mW switch power, approximately 42 micros switch time for the MI with deep trenches, 13.14 mW switch power and approximately 34 micros switch time for the MI without deep trenches were achieved.

Low loss (approximately 6.45dB/cm) sub-micron polycrystalline silicon waveguide integrated with efficient SiON waveguide coupler.

In this communication, the sub-micron size polycrystalline silicon (poly- Si) single mode waveguides are fabricated and integrated with SiON waveguide coupler by deep UV lithography. The propagation loss of poly-Si waveguide and coupling loss with optical flat polarization-maintaining fiber (PMF) are measured. For whole C-band (i.e., lambda approximately 1520-1565nm), the propagation loss of TE mode is measured to approximately 6.45+/-0.3dB/cm. The coupling loss with optical flat PMF is approximately 3.4dB/facet for TE mode. To the best of our knowledge, the propagation loss is among the best reported results. This communication discusses the factors reducing the propagation loss, especially the effect of the refractive index contrast. Compared to the SiO(2) cladding, poly-Si waveguide with SiON cladding exhibits lower propagation loss.

Proposed silicon wire interleaver structure.

A Ring-resonator Mach-Zehnder interferometer (RR-MZI) optical interleaver structure comprising a ring resonator (RR) and a 3 dB directional coupler is proposed. The interleaver is fabricated with 300 nm x 300 nm silicon wires on silicon-on-insulator (SOI) wafers. The fabricated interleaver demonstrates a flat-top spectral response, and the measured free spectral range (FSR) is approximately 20 nm. The insertion loss (IL) of the device is approximately -10 dB and the polarization dependent loss (PDL) <5 dB. Both the experimental and simulation results are in good agreement.