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Introduction: Cryptococcal meningitis (CM) is a serious and fatal fungal infection that affects individuals infected with human immunodeficiency virus (HIV). Despite treatment, recurrence of symptoms is common and could lead to poor outcomes. Corticosteroids are not always useful in treating symptom recurrence following HIV/CM; thus, alternative therapy is needed. Thalidomide has been reported to be effective in treating symptom recurrence in several patients with HIV/CM. This retrospective study aimed to investigate the efficacy and safety of thalidomide in the treatment of symptom recurrence following HIV/CM. Methods: Patients who were treated with thalidomide for symptom recurrence following HIV/CM were retrospectively included. Clinical outcomes and adverse events were recorded and analyzed. Results: Sixteen patients admitted between July 2018 and September 2020 were included in the analysis. During a median follow-up period of 295 (166, 419) days, all patients achieved clinical improvement in a median of 7 (4, 20) days. Among them, nine (56%) achieved complete resolution of symptoms at a median of 187 (131, 253) days, including 40% (2/5) of immune reconstitution inflammatory syndrome (IRIS), 50% (3/6) of patients with elevated ICP only, and 80% (4/5) of patients with symptoms only. Seven (43%) patients experienced nine episodes of adverse events, but no severe adverse event attributable to thalidomide was observed. None of the patients withdrew from thalidomide due to adverse events. Conclusion: Thalidomide appears to be effective and safe in treating different types of symptom recurrence in HIV/CM. This study provides preliminary evidence supporting future randomized clinical trials to further investigate the efficacy and safety of thalidomide in treating symptom recurrence in this population.

Introduction: This study aimed to evaluate the prevalence of HIV-1 mutation V179D/E and the effect of V179D/E on the virological response to first-line efavirenz-based regimens among antiretroviral treatment (ART)-naïve patients. Methods: An ambispective cohort study was conducted. All ART-naïve patients who underwent baseline genotypic resistance testing between January 2019 and November 2021 were included in the analysis of the prevalence of the V179D/E mutation. Then, patients with identified V179D/E received the efavirenz-based regimen or the protease inhibitor (PI)/integrase strand transfer inhibitor (INSTI)-based regimen. The virological and immunological outcomes at week 48 were compared between the two groups. Results: HIV-1 mutation V179D/E was identified in 252 out of 2568 ART-naïve patients, with a prevalence of 9.8% in Shanghai, China. A total of 206 participants were included in the efficacy analysis. Forty-six patients with altered ART regimens or incomplete follow-up data were excluded from the analysis. The baseline characteristics were comparable between the efavirenz group (n= 109) and the PI/INSTI group (n= 97). At week 48, a total of 96 participants (88.1%) in the efavirenz group and 92 participants (94.8%) in the PI/INSTI group had a viral load lower than 50 copies/mL (chi-square test, p= 0.086). In both groups, a lower proportion of participants achieved virological suppression among participants with a baseline viral load of at least 100,000 copies/mL compared with those with lower than 100,000 copies/mL (66.7% vs. 96.1% in the efavirenz group, p< 0.001; 87.1% vs. 98.4% in the PI/INSTI group, p= 0.039). The median increase from baseline in the CD4 count at week 48 was significantly greater in the PI/INSTI group (192 cells/μL) than in the efavirenz group (154 cells/μL) (p= 0.029). Conclusion: There is a high prevalence of V179D/E in ART-naïve patients with HIV-1 in Shanghai, China. The first-line efavirenz-based regimen may be not suitable for patients with HIV-1 mutation V179D/E, especially for those with a baseline viral load of at least 100,000 copies/mL. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2000034787).

The southern waters of the Sumatra‐Java Islands, within the Indo‐Pacific Warm Pool, are highly susceptible to global climate change impacts. Understanding particulate inorganic carbon (PIC) dynamics and environmental responses in this region is critical for assessing climate change effects on marine ecosystems. Utilizing two decades of remote sensing PIC data (2003–2022), we identified five sub‐regions via K‐means clustering: the Sunda Strait, southern coastal/offshore waters of Sumatra Island, and southern coastal/offshore waters of Java Island. Self‐Organizing Map explored interannual PIC variations, while Generalized Additive Models delineated driving factors. In the Sunda Strait, PIC dynamics are influenced by water exchanges between the Indonesian Seas (ISs) and eastern Indian Ocean (EIO). Seasonally, PIC concentrations peak during the east monsoon (boreal summer); decreasing during positive Indian Ocean Dipole (+IOD) and El Niño events. Along the southern Sumatra, PIC variations positively correlate with rainfall and photosynthetically active radiation (PAR). Along the southern Sumatra, upwelling drives PIC variations, with higher concentrations during mature summer monsoon induced upwelling periods. PIC increases during +IOD and decreases during El Niño. Our study highlights the nexus between nutrients, physical factors (e.g., rainfall), and climatic events (e.g., El Niño) on PIC concentrations. Climate‐induced changes in oceanic physical processes modulate nutrient concentrations, thereby governing PIC variations. We propose a mechanistic model to elucidate PIC variations in upwelling areas. Findings suggest that prospective climate variability, encompassing alterations in climate events, rainfall, and temperature, may escalate PIC concentrations within the study area, advocating PIC as a forward‐looking climate change indicator. Understanding the response of particulate inorganic carbon (PIC)—a primary form of oceanic carbon ‐ to environmental changes in the vulnerable southern waters of the Sumatra‐Java Islands is crucial for assessing the marine ecosystem. We used satellite image data to examine the variability of PIC, from 2003 to 2022. Our research showed that PIC concentrations varied across the area. In the Sunda Strait, a narrow body of water between land masses, water movement between the Indonesian Seas and eastern Indian Ocean influences PIC concentrations. In the southern waters of Sumatra Island, we discovered that increased rainfall and sunlight contribute to higher PIC concentrations. In the southern waters of Java Island, upwelling, an ocean physical process that brings nutrient‐rich water to the surface, plays a significant role. Our study delineates the interplay between nutrients, physical factors (e.g., rainfall), and climatic events (e.g., El Niño) on coccolithophore biomass. Climate changes drive alterations in oceanic physical processes, which in turn affect nutrient availability, thereby governing the growth of coccolithophores. Findings suggest prospective climate variability, inclusive of alterations in climate events, rainfall, and temperature, may escalate PIC concentrations within the study area, advocating PIC concentrations alterations as a forward‐looking climate change indicator. Climate alters oceanic physical processes, thereby modulating nutrient availability, which in turn directly governs Particulate Inorganic Carbon (PIC) variationsA 20‐year analysis identified three core mechanisms driving PIC spatiotemporal variations in the study areaRising PIC under future climates predicts higher carbon sedimentation rates, marking PIC as a key climate indicator Climate alters oceanic physical processes, thereby modulating nutrient availability, which in turn directly governs Particulate Inorganic Carbon (PIC) variations A 20‐year analysis identified three core mechanisms driving PIC spatiotemporal variations in the study area Rising PIC under future climates predicts higher carbon sedimentation rates, marking PIC as a key climate indicator

Biogeochemical Si cycle in coastal areas is of vital importance due to its close link with the carbon cycle. However, the coastal Si cycle has been heavily perturbated by human activities. In this study, we studied the spatiotemporal distribution of biogenic Si (BSi) and dissolved Si (DSi) combined with stable Si isotopes of DSi (δ30SiDSi) in the Yellow River estuary and Bohai Sea, one of the most populated coastal areas in the world. Over an annual cycle, BSi and DSi concentrations varied from 0 to 43.5 μmol L−1and from 0.3 to 40 μmol L−1, respectively. This was associated with large δ30SiDSivariations from +0.49 ± 0.22‰ (2sd) in spring to +2.92 ± 0.14‰ in winter, which opposed to observations that summer δ30SiDSivalues were usually higher than those in winter. This atypical variation could be attributed to the water‐sediment regulation on the Yellow River occurring every early summer, leading to a strong water mixing pattern and suppressing diatom production in summer. This mixing was further prolonged by extreme autumn rainfall on land. The pulse supply of nutrients subsequently enhanced primary productivity from autumn through winter. In spring, the resuspended seafloor sediments were likely an important DSi source with δ30Si values of <−0.5‰. Our findings suggest that natural Si seasonality has been greatly masked by human activities and climate events in the Bohai Sea. Our study serves as a reference of the Si cycle research endeavors worldwide for revealing the overlaying effect of anthropogenic consequences and natural variability. Three quarters of carbon in coastal areas are removed from the atmosphere through diatoms that utilize silicon as an essential nutrient. However, the biogeochemical silicon cycle in coastal areas has been strongly altered by human activities in recent decades. This study chooses one of the most perturbated coastal areas, the Yellow River estuary and Bohai Sea, to assess the status of today's silicon cycle using stable silicon isotopes. We find higher silicon consumption in winter than that in summer, which is opposite to natural patterns. This is attributed to the water‐sediment regulation on the Yellow River occurring in early summer every year. Pulse inputs of water and particles lead to strong water mixing and increased water turbidity, hindering primary production in the river mouth and Bohai Sea in summer. Such effects can be further extended by heavy rainfall and water floods from land in early autumn. When the water calms down, diatom production emerges in autumn and winter. Our study demonstrates that human perturbations can superimpose natural patterns of the silicon cycle in coastal areas, which is further complicated by extreme climate events. This “artificial” phenomenon should be included in coastal nutrient budgets over seasonal to annual time scales. The water‐sediment regulation on the Yellow River plays a crucial role in variation of the Si cycle in the river estuary and Bohai SeaThe Si distribution is dominated by water mixing in summer and to a large extent in autumn, but by diatom production in winter and springDesorbed Si from resuspended seafloor sediments is likely responsible for low δ30SiDSivalues observed in winter and spring The water‐sediment regulation on the Yellow River plays a crucial role in variation of the Si cycle in the river estuary and Bohai Sea The Si distribution is dominated by water mixing in summer and to a large extent in autumn, but by diatom production in winter and spring Desorbed Si from resuspended seafloor sediments is likely responsible for low δ30SiDSivalues observed in winter and spring

Yb-doped inorganic crystals have attracted great attention in both basic and applied research, and the quest for suitable crystal hosts and understanding the corresponding crystal field environments are still worth studying in laser application. In this context, inclusion-free RbTiOPO4:Ta:Yb (RTP:Ta:Yb) single crystals with dimensions up to 3 × 30 × 15 mm3were grown by top-seeded solution growth method under optimized growth conditions. The good crystalline quality of the as-grown RTP:Ta:Yb crystals were confirmed by X-ray diffraction rocking curve. The chemical compositions of the crystals were determined through electron probe microanalysis (EPMA). The results showed that the Ta distribution coefficient is 0.90–1.28, and the Yb distribution coefficient is 0.13–0.37. Double doping of Ta5+ions can effectively increase the concentration of Yb3+ions in the RTP crystal, and the concentration of Yb3+ion in RTP crystal can reach 1.26 × 1020atom/cm3. The influence of Ta and Yb dopants on the electronic structures of RTP crystals was studied using high-resolution X-ray photoelectron spectroscopy (XPS), and the chemical strengths of Ti–O and P–O bonds are related to the binding energy difference. RTP:Ta:Yb crystals exhibit excellent transparent performance in the wavelength range of 0.35–4.5 μm, and the transmittance is about 83%. Photoluminescence spectra show five emission peaks of Yb3+in crystals, and the main emission peak is located at 972 nm. Two different coordination sites for Yb3+were observed, and their energy levels were determined in the crystal field of the RTP:Ta structure. Furthermore, the crystal field strengths of Yb3+in different host crystals associated with their distorted coordination environments were evaluated and discussed in detail. The results demonstrate that the RTP:Ta:Yb single crystal endowed with high crystal field strength and good luminescence property is suitable for laser application.

Trace metals in the groundwater of coastal sandy aquifers significantly influence the coastal ecosystem, yet the spatiotemporal controls of these metals remain unclear. In this paper, we comprehensively revealed the distribution patterns, key controlling factors, potential ecological risks, and fluxes to the ocean of groundwater trace metals (As, Ba, Cr, Cd, Fe, Mn, Pb, and Zn) in a coastal deep sandy aquifer. The results showed a clear zonation of trace metals in the groundwater in relation to the mixing extent between seawater and terrestrial freshwater. The freshwater zone exhibited a relatively low concentration of trace metals, whereas the freshwater‐seawater transition zone showed a substantial quantity of dissolved Fe, Mn, As, and Ba. Seawater‐groundwater interactions significantly affected the Fe, Mn, As, and Ba concentrations through redox potential and pH gradients. The tide‐driven saline water zone was vulnerable to oceanic environments and anthropogenic activities, resulting in the enrichment of trace metals such as Zn and Cd. Driven by recirculated submarine groundwater discharge (SGD), the concentrations of trace metals in the density‐driven saline circulation zone were found to be higher than those in the surrounding areas. The ecological risk index suggested that the freshwater‐seawater transition zone posted the highest ecological risks. Trace metal fluxes (i.e., Fe, Mn, and As) via SGD significantly contributed to the total input into the sea, which may have potential impacts on the coastal environments. Our study highlighted the importance of seawater‐groundwater interactions on trace element cycling in coastal sandy aquifers. The distribution of groundwater trace metals in a coastal deep sandy aquifer with different seasons was investigated, and four zones were identifiedKey controlling factors, ecological risks, and fluxes of trace metals in different zones were evaluatedSeawater‐groundwater interactions aiding trace metal addition/removal insfluenced trace element cycling on a sandy coast The distribution of groundwater trace metals in a coastal deep sandy aquifer with different seasons was investigated, and four zones were identified Key controlling factors, ecological risks, and fluxes of trace metals in different zones were evaluated Seawater‐groundwater interactions aiding trace metal addition/removal insfluenced trace element cycling on a sandy coast

In2O3material with special morphology was synthesized using the hydrothermal method and was used as the sensing electrode for a mixed potential ammonia sensor based on yttria-stabilized zirconia electrolyte. The In2O3sensing electrode (In2O3-SE) was sintered at different temperatures and was characterized by X-ray diffraction (XRD) and field-emission scanning electron microscopy (SEM). The influence of the In2O3-SE sintering temperature on the performance of the sensor was investigated by testing the NH3response at 500 °C. The results showed that the sensor attached with In2O3-SE sintered at 900 °C exhibited the largest response value (–102.1 mV for 250 ppm NH3) at 500 °C. Moreover, the response value of the sensor varied almost linearly with the logarithm of NH3concentration in the range of 20–400 ppm, which was consistent with the mixed potential mechanism, as verified by polarization and electrochemical impedance spectroscopy (EIS) tests. Furthermore, the sensor also displayed high sensitivity to NH3, but weak cross-sensitivities to various interfering gases (CHs, NOx, CO, CO2and H2O) at 500 °C. It exhibited slight signal drifts both in the continuous 26-h test and in the interval test over a period of one month, which showed that the sensor attached with 900 °C-sintered In2O3-SE has acceptable short- and long-term stability.

The purpose of this study was to investigate the frequency of CYP2B6polymorphisms and their influence on plasma concentrations of efavirenz and nevirapine in HIV-infected Chinese patients. After written informed consent, 159 patients were enrolled at Shanghai Public Health Clinical Center. Genotyping for 516 G>T, 785 A>G, 983 T>C, and 1459 T>C polymorphisms in CYP2B6, together with CYP3A4−392 A>G, CYP3A56986 A>G, and ABCB1(2677 G>T/A, 3435 C>T), were performed. Plasma efavirenz and nevirapine concentrations of 120 patients at steady state were assessed by high-performance liquid chromatography-mass spectrometry. The minor allele frequency for CYP2B6516 G>T, 785 A>G, 983 T>C, and 1459 T>C was 0.16, 0.24, 0, and 0, respectively; and 0.07, 0.32, 0.15, and 0.35 for CYP3A4−392 A>G, CYP3A56986 A>G, ABCB12677 G>T/A, and ABCB13435 C>T, respectively. Univariate analysis indicated associations between 516 G>T (P< 0.01) with efavirenz but not nevirapine plasma concentrations. None of other genetic variants was associated with plasma efavirenz or nevirapine concentrations. Although CYP2B6516 G>T was associated with high plasma efavirenz concentrations, such an association was not evident with nevirapine in this Chinese patient population. CYP3A4−392 A>G, CYP3A56986 A>G, and ABCB1(2677 G>T/A, 3435 C>T) had no significant impact on plasma efavirenz or nevirapine concentrations.

We report on the elemental redistribution behavior in oxyfluoride glasses with a high repetition rate near-infrared femtosecond laser. Elemental analysis by an electro-probe microanalyzer demonstrates that the redistributions of Ca^2+ and Yb^3+ ions change dramatically with pulse energy, which are quite different compared with previous reported results. Confocal fluorescence spectra of Yb^3+ ions demonstrate that the luminescence intensity changes obviously with the elemental redistribution. The mechanism of the observed phenomenon is discussed. This observation may have potential applications in the fabrication of micro-optical devices.