Evolution of groundwater system in the Pearl River Delta and its adjacent shelf since the late Pleistocene.

Our extensive field studies demonstrate that saline groundwater inland and freshened groundwater offshore coexist in the same aquifer system in the Pearl River delta and its adjacent shelf. This counterintuitive phenomenon challenges the commonly held assumption that onshore groundwater is typically fresh, while offshore groundwater is saline. To address this knowledge gap, we conduct a series of sophisticated paleo-hydrogeological models to explore the formation mechanism and evolution process of the groundwater system in the inland-shelf systems. Our findings indicate that shelf freshened groundwater has formed during the lowstands since late Pleistocene, while onshore saline groundwater is generated by paleo-seawater intrusion during the Holocene transgression. This reveals that terrestrial and offshore groundwater systems have undergone alternating changes on a geological timescale. The groundwater system exhibits hysteresis responding to paleoclimate changes, with a lag of 7 to 8 thousand years, suggesting that paleoclimatic forcings exert a significantly residual influence on the present-day groundwater system.

A comparison analysis of the somatic mutations in early-onset gastric cancer and traditional gastric cancer.

BACKGROUND: Early onset gastric cancer (EOGC) has been on the rise in recent years and differs slightly in pathology from traditional gastric cancer (TGC). Somatic mutations have an essential role in the development of gastric cancer. We aimed to investigate these two types of gastric cancers at the level of somatic mutations and to further understanding of gastric cancer development. METHODS: Somatic mutation, copy number variation (CNV), and clinical information were obtained from TCGA and UCSC Xena. Samples were divided into EOGC (< 50 years old, N = 28) and TGC (≥ 50 years old, N = 395) groups based on age. R packages "maftools" and "sigminer" were used to identify mutation signatures, while CNV information was processed using GISTIC2.0. RESULTS: CDH1(21 %, P = 0.030) and ARID1A (28 %, P = 0.014) were more common in EOGC and TGC, respectively. The mutation frequency of ARID1A increased with age, while the opposite was true for CDH1. Sex, Lauren classifications, tumor mutation burden levels, mutation status of TP53, MUC6, NIPBL, KRAS, and copy number variation of the WOOX can affect the activity of the mutant signature. CONCLUSIONS: Early-onset gastric cancer and traditional gastric cancer have distinct somatic mutation signatures, each with its own relatively specific high-frequency mutated genes, and the gene's mutation frequency correlates with age. Several clinical factors and genetic status affect the activity of some mutational features in gastric cancer in both groups.

Third ventricular width by transcranial sonography is associated with cognitive impairment in Parkinson's disease.

BACKGROUND: One-fourth of Parkinson's disease (PD) patients suffer from cognitive impairment. However, few neuroimaging markers have been identified regarding cognitive impairment in PD. OBJECTIVE: This study aimed to explore the association between third ventricular width by transcranial sonography (TCS) and cognitive decline in PD. METHOD: Participants with PD were recruited from one medical center in China. Third ventricular width was assessed by TCS, and cognitive function was analyzed by the Mini-Mental State Examination (MMSE). Receiver operating characteristic (ROC) analysis and Cox model analysis were utilized to determine the diagnostic and predictive accuracy of third ventricular width by TCS for cognitive decline in PD patients. RESULT: A total of 174 PD patients were recruited. Third ventricular width was negatively correlated with MMSE scores. ROC analysis suggested that the optimal cutoff point for third ventricular width in screening for cognitive impairment in PD was 4.75 mm (sensitivity 62.7%; specificity 75.6%). After 21.5 (18.0, 26.0) months of follow-up in PD patients without cognitive impairment, it was found that those with a third ventricular width greater than 4.75 mm exhibited a 7.975 times higher risk of developing cognitive impairment [hazard ratio = 7.975, 95% CI 1.609, 39.532, p = 0.011] compared with patients with a third ventricular width less than 4.75 mm. CONCLUSION: Third ventricular width based on TCS emerged as an independent predictor of developing cognitive impairment in PD patients.

Global burden of stomach cancer attributable to smoking from 1990 to 2019 and predictions to 2044.

OBJECTIVES: This study aimed to assess the global temporal trends of stomach cancer attributable to smoking from 1990 to 2019 and to predict the global burden by 2044. STUDY DESIGN: This was a comprehensive analysis based on data provided by the Global Burden of Disease Study 2019. METHODS: Based on the Global Burden of Disease Study 2019, mortality, disability-adjusted life years (DALYs), and corresponding age-standardised rates of stomach cancer attributable to smoking by sociodemographic index (SDI), region, country, sex, and age were used to assess temporal trends from 1990 to 2019 by calculating the average annual percentage change (AAPC). In addition, the global burden of stomach cancer attributable to smoking up to 2044 was predicted using age-period-cohort models. RESULTS: Globally, in 2019, 17.96% of stomach cancer deaths (1.72 million) and 17.15% of stomach cancer DALYs (38.13 million) were attributable to smoking, representing an increase compared to 1990; however, smoking-attributable age-standardised rates of mortality (ASMRs) and DALYs (ASDRs) significantly declined to 2.12/100,000 and 45.82/100,000 in 2019, respectively. While stomach cancer ASMR and ASDR attributable to smoking decreased in all regions and in most countries, they increased by >10% in some countries. A positive correlation was found between SDI and age-standardised rates (rASMR = 0.28, P < 0.01; rASDR = 0.29, P < 0.01). By 2044, although global age-standardised rates for smoking-attributable stomach cancer are predicted to decline, deaths and DALYs are estimated to increase to 2.22 million and 42.14 million, respectively. CONCLUSIONS: Stomach cancer deaths and DALYs attributable to smoking have increased over the past 30 years and will continue to increase. Consequently, targeted prevention efforts and tobacco-control strategies need to be further developed and improved.

Prognostic value of lncRNA AFAP1-AS1 in breast cancer: a meta-analysis and validated study in Chinese population.

BACKGROUND: Long non encoding RNA (lncRNA) plays a crucial role in breast cancer. However, the prognostic role of AFAP1-AS1 in breast cancer remains unclear. AIMS: To investigate the relationship between the expression of long non-coding RNA actin filament-associated protein1 antisense RNA1 (AFAP1-AS1) and prognosis of breast cancer. METHODS AND RESULTS: Meta-analysis was performed to explore the correlation between AFAP1-AS1 and breast cancer. The AFAP1-AS1expression in patients with breast cancer tissue and adjacent normal tissue from 153 patients was determined by qRT-PCR. Bioinformatics and Cox proportional-hazards risk model were used to explore the relationship between expression of AFAP1-AS1 and prognosis. The combined analysis revealed a significant correlation between AFAP1-AS1 expression and both overall survival (hazard ratios, HR = 2.33, 95%Cl: 1.94-2.81, p < 0.001) as well as disease-free survival/progression-free survival (HR = 2.94, 95%CI: 2.35-3.67, p < 0.001). The relation between expression of AFAP1-AS1 and breast cancer was determined in 153 breast cancer and adjacent normal tissues. The findings revealed a significantly higher AFAP1-AS1expression levels in breast cancer tissues compared to adjacent normal tissues (p < 0.001). Additionally, patients exhibiting heightened levels of AFAP1-AS1 expression were correlated with an unfavorable prognosis (HR = 2.35, 95%CI: 1.47-3.74, p < 0.001), which aligns consistently with the findings of the pooled analysis. The subgroup analysis of clinical characteristics revealed a significant association between high expression of AFAP1-AS1 and TNM stage (HR = 1.72, 95%CI: 1.11-2.65, p = 0.015). CONCLUSION: This study demonstrated that AFAP1-AS1 acts as an oncogene and may serve as a novel prognostic marker for breast cancer, particularly in the Chinese population.

Observation of a Photonic Orbital Gauge Field.

Gauge field is widely studied in natural and artificial materials. With an effective magnetic field for uncharged particles, many intriguing phenomena are observed in several systems like photonic Floquet topological insulator. However, previous researches about the gauge field mostly focus on limited dimensions such as the Dirac spinor in graphene materials. Here, an orbital gauge field based on photonic triangular lattices is first proposed and experimentally observed. Disclination defects with Frank angle Ω created on such lattices breaks the original lattice symmetry and generates purely geometric gauge field operating on orbital basis functions. Interestingly, it is found that bound states near zero energy with the orbital angular momentum (OAM) l = 2 are intensively confined at the disclination as gradually expanding Ω. Moreover, the introduction of a vector potential field breaks the time-reversal symmetry of the orbital gauge field, experimentally manifested by the chiral transmission of light on helical waveguides. The orbital gauge field further suggests fantastic applications of manipulating the vortex light in photonic integrated devices.

Offshore freshened groundwater in the Pearl River estuary and shelf as a significant water resource.

Large-river deltaic estuaries and adjacent continental shelves have experienced multiple phases of transgressions and regressions to form interlayered aquifer-aquitard systems and are expected to host vast paleo-terrestrial groundwater hundreds of kilometres offshore. Here, we used offshore hydrogeology, marine geophysical reflections, porewater geochemistry, and paleo-hydrogeological models, and identified a previously unknown offshore freshened groundwater body with a static volume up to 575.6 ± 44.9 km3 in the Pearl River Estuary and adjacent continental shelf, with the freshwater extending as far as 55 km offshore. An integrated analysis of stable isotopic compositions and water quality indices reveals the meteoric origins of such freshened groundwater and its significance as potential potable water or raw water source for desalination. Hotspots of offshore freshened groundwater in large-river deltaic estuaries and adjacent continental shelves, likely a global phenomenon, have a great potential for exploitable water resources in highly urbanized coastal areas suffering from freshwater shortage.

Efficacy and safety of ustekinumab in the treatment of moderate to severe plaque psoriasis in Singapore

INTRODUCTION@#Ustekinumab is a human monoclonal antibody that binds to the p40 subunit of both interleukin (IL)-12 and IL-23, and it is approved for the treatment of moderate to severe plaque psoriasis. In this study, we assessed the efficacy and safety of patients receiving ustekinumab for psoriasis.@*METHODS@#This retrospective study included all adults with chronic plaque psoriasis who were prescribed ustekinumab in a tertiary dermatologic centre between December 2009 and December 2015. Efficacy end points included a proportion of patients achieving at least 50% and 75% improvement from baseline psoriasis area and severity index (PASI) and body surface area (BSA) at Weeks 4 and 16.@*RESULTS@#A total of 99 patients were prescribed ustekinumab; 69% of these were Chinese, followed by 15% Indians and 9% Malays. 31 patients had documented PASI scores and 55 patients had documented BSA improvements. In patients with recorded PASI scores, 29 (93.5%) of 31 patients achieved PASI 50, and 21 (67.7%) of 31 achieved PASI 75 at week 16. In patients with recorded BSA, 43 (78.2%) of 55 had at least 50% BSA improvement, and 31 (56.4%) of 55 achieved 75% BSA improvement at 16 weeks. Regarding safety, no patient experienced tuberculosis reactivation. A total of 11 (11%) of 99 patients had latent tuberculosis infection and were treated with prophylactic isoniazid. No patient experienced serious adverse events. No cardiovascular events, cutaneous malignancies or deaths were reported over six years.@*CONCLUSION@#Ustekinumab is safe and efficacious in the treatment of patients with moderate to severe plaque psoriasis in a multiethnic Asian population.

Bound vortex light in an emulated topological defect in photonic lattices.

Topology have prevailed in a variety of branches of physics. And topological defects in cosmology are speculated akin to dislocation or disclination in solids or liquid crystals. With the development of classical and quantum simulation, such speculative topological defects are well-emulated in a variety of condensed matter systems. Especially, the underlying theoretical foundations can be extensively applied to realize novel optical applications. Here, with the aid of transformation optics, we experimentally demonstrated bound vortex light on optical chips by simulating gauge fields of topological linear defects in cosmology through position-dependent coupling coefficients in a deformed photonic graphene. Furthermore, these types of photonic lattices inspired by topological linear defects can simultaneously generate and transport optical vortices, and even can control the orbital angular momentum of photons on integrated optical chips.

Mechanism of Photoinduced Phase Segregation in Mixed-Halide Perovskite Microplatelets and Its Application in Micropatterning.

Photoinduced phase segregation (PPS) is considered as a dominant factor that greatly deteriorates the performances of mixed-halide perovskite devices. However, the mechanism of PPS is still under fierce debate. Herein, CsPb(Brx/Cl1-x)3 microplatelets (MPs) with homogeneous and heterogeneous surfaces are obtained by controlling the growth conditions. Under continuous irradiation, a new photoluminescence (PL) band at 516 nm gradually appears in the heterogeneous MPs, accompanied with the decreased emission of the mixed phase at 480 nm, revealing the occurrence of PPS, while the photoirradiation only leads to slight PL dimming without PPS in the homogeneous MPs. The direct correlation between PPS and the structural heterogeneity indicates that the localized electric field-induced drift (LEFD) of halide ions/carriers is responsible for the PPS. In situ microfluorescence images evidence that the migration of halide ions is directed by the structural heterogeneity-induced localized electric field. Our refined model not only consolidates that PPS can be suppressed by eliminating the defects but also reveals that PPS can be directed by the distribution of defects. Therefore, a fluorescence micropatterning technique is developed based on PPS.

Novel transdermal device for delivery of triamcinolone for nail psoriasis treatment

INTRODUCTION@#Nail psoriasis treatment is challenging due to difficult drug delivery and systemic therapy toxicities. Self-dissolvable microneedle patches embedded with corticosteroids offers a potentially rapid, minimally invasive drug delivery platform with good efficacy and minimal adverse side effects.@*METHODS@#We conducted a 4-month prospective randomised controlled trial. Subjects with psoriatic nails were randomised to receive microneedle device delivered topical steroids on one hand and control treatment (topical Daivobet gel) on the other. Two independent dermatologists blinded to the treatment assignment scored their Nail Psoriasis Severity Index (NAPSI) during visits at baseline, 2 and 4 months. All treatment was discontinued after 2 months. Average NAPSI score on each hand was analysed.@*RESULTS@#A total of 25 participants were recruited, aged 22 to 73 years. Majority were Chinese (72%), followed by Indian and Malay. There was equal randomisation of treatment to the left and right nail. While there was a rapid significant improvement in average NAPSI score for the control arm at 2 months, the treatment arm had a greater, more sustained improvement of the NAPSI score at 4 months. The average NAPSI score improved for both treatment and control group at 4 months compared to baseline. However, only the NAPSI value improvement in the controls at 2 months compared to baseline was statistically significant (P=0.0039). No severe adverse effects were reported.@*CONCLUSION@#To the best of our knowledge, this is the first prospective randomised control trial comparing microneedle technology against conventional topical steroids in nail psoriasis treatment. Our findings demonstrate microneedle technology is as efficacious as topical therapy.

Observation of the acceleration of light in a tapered optical fiber.

One of the most fascinating aspects of quantum fields in curved spacetime is the Unruh effect. The direct experimental detection of Unruh temperature has remained an elusive challenge up to now. Gradient optical waveguides manipulating the dispersion of photons are assumed to realize the great acceleration of effective particles, leading to a high effective Unruh temperature. However, experimentally achieving this optical waveguide has not yet been reported. In this work, we exploit a tapered fiber to simulate the accelerated motion of effective particles and obtain an effective Unruh temperature. When light propagating in a tapered fiber is affected by the external high refractive index medium, a leaky phenomenon akin to bremsstrahlung will be observed, and the pattern of leaky radiation is dependent on the acceleration of photons. During the experiments, different accelerations corresponding to different Unruh temperatures are achieved by controlling the shape of the tapered waveguide.

Microsteganography on all inorganic perovskite micro-platelets by direct laser writing.

Direct laser writing (DLW) is a mask-free and cost-efficient micro-fabrication technology, which has been explored to pattern structures on perovskites. However, there is still a lack of research on DLW methods for microsteganography. Herein, we developed a sophisticated DLW condition to pattern on CsPbBr3 perovskite micro-platelets (MPs). In addition to the reversible PL quenching caused by photo-induced ion migration, permanent nonradiative centers are also produced by the DLW treatment. Therefore, the patterned information is retained after long-term storage. Meanwhile, the mild DLW condition only results in a faint trace, which is almost invisible under a regular optical microscope. Thus, the patterned information is hidden unless applying an excitation source, which paves the way for applications in microsteganography and anti-counterfeiting. As a proof-of-concept, different patterns are drawn on the CsPbBr3 MPs by DLW, which are only observable under a fluorescence microscope.

Enhanced directional quantum emission by tunable topological doubly resonant cavities.

How to utilize topological microcavities to control quantum emission is one of the ongoing research topics in the optical community. In this work, we investigate the emission of quantum emitters in a doubly-resonant topological Tamm microcavity, which can simultaneously achieve dual resonances at two arbitrary wavelengths according to the needs of practical application. To achieve the enhancement of quantum emission in such cavities, we have exploited the tunable doubly-resonant modes, in which one of resonant modes corresponds to the pump laser wavelength and the other one is located at the emission wavelength of quantum emitters. Both theoretical and experimental results demonstrate that the pump excitation and emission efficiencies of quantum emitters are greatly enhanced. The main physical mechanism can be explained by the doubly-resonant cavity temporal coupled-mode theory. Furthermore, we observe the faster emission rate and the higher efficiency of unidirectional quantum emission, which have promising applications in optical detection, sensing, filtering, and light-emitting devices.

Maximum expected entropy transformed Latin hypercube designs.

Existing projection designs (e.g. maximum projection designs) attempt to achieve good space-filling properties in all projections. However, when using a Gaussian process (GP), model-based design criteria such as the entropy criterion is more appropriate. We employ the entropy criterion averaged over a set of projections, called expected entropy criterion (EEC), to generate projection designs. We show that maximum EEC designs are invariant to monotonic transformations of the response, i.e. they are optimal for a wide class of stochastic process models. We also demonstrate that transformation of each column of a Latin hypercube design (LHD) based on a monotonic function can substantially improve the EEC. Two types of input transformations are considered: a quantile function of a symmetric Beta distribution chosen to optimize the EEC, and a nonparametric transformation corresponding to the quantile function of a symmetric density chosen to optimize the EEC. Numerical studies show that the proposed transformations of the LHD are efficient and effective for building robust maximum EEC designs. These designs give projections with markedly higher entropies and lower maximum prediction variances (MPV's) at the cost of small increases in average prediction variances (APV's) compared to state-of-the-art space-filling designs over wide ranges of covariance parameter values.

Quantum simulation of particle pair creation near the event horizon.

Though it is still a big challenge to unify general relativity and quantum mechanics in modern physics, the theory of quantum field related with the gravitational effect has been well developed and some striking phenomena are predicted, such as Hawking radiation. However, the direct measurement of these quantum effects under general relativity is far beyond present experiment techniques. Fortunately, the emulation of general relativity phenomena in the laboratory has become accessible in recent years. However, up to now, these simulations are limited either in classical regime or in flat space whereas quantum simulation related with general relativity is rarely involved. Here we propose and experimentally demonstrate a quantum evolution of fermions in close proximity to an artificial black hole on a photonic chip. We successfully observe the acceleration behavior, quantum creation, and evolution of a fermion pair near the event horizon: a single-photon wave packet with positive energy escapes from the black hole while negative energy is captured. Our extensible platform not only provides a route to access quantum effects related with general relativity, but also has the potentiality to investigate quantum gravity in future.

Definite photon deflections of topological defects in metasurfaces and symmetry-breaking phase transitions with material loss.

Combination of topology and general relativity can lead to some profound and farsighted predictions. It is well known that symmetry breaking of the Higgs vacuum field in the early universe possibly induced topological defects in space-time, whose nontrivial effects can provide some clues about the universe's origin. Here, by using an artificial waveguide bounded with rotational metasurface, the nontrivial effects of a topological defect of spacetime are experimentally emulated. The photon deflection in the topological waveguide has a robust definite angle that does not depend on the location and momentum of incident photons. This is remarkably different from the random optical scattering in trivial space. By including material loss such a topological effect can be well understood from the symmetry breaking of photonic modes. Our technique provides a platform to investigate topological gravity in optical systems. This method can also be extended to obtain many other novel topological photonic devices.

Self-Focusing and the Talbot Effect in Conformal Transformation Optics.

Transformation optics has been used to propose various novel optical devices. With the help of metamaterials, several intriguing designs, such as invisibility cloaks, have been implemented. However, as the basic units should be much smaller than the working wavelengths to achieve the effective material parameters, and the sizes of devices should be much larger than the wavelengths of illumination to work within the light-ray approximation, it is a big challenge to implement an experimental system that works simultaneously for both geometric optics and wave optics. In this Letter, by using a gradient-index microstructured optical waveguide, we realize a device of conformal transformation optics (CTO) and demonstrate its self-focusing property for geometry optics and the Talbot effect for wave optics. In addition, the Talbot effect in such a system has a potential application to transfer digital information without diffraction. Our findings demonstrate the photon controlling ability of CTO in a feasible experiment system.