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Personalized antitumor immunotherapy utilizing neoantigen vaccines holds great promise. However, the limited immunogenicity of existing recognized neoantigens and the inadequate stimulation of antitumor immune responses by conventional adjuvants pose significant challenges. To address these limitations, we developed a nanovaccine that combines a BCG bacterial cell wall skeleton (BCG-CWS) based nanoscale adjuvant (BCNA) with peptide neoantigens (M27 and M30). This integrated approach provides an efficient translational strategy for cancer immunotherapy. The BCNA nanovaccine, formulated with PLGA as an emulsifier, exhibits excellent biocompatibility and superior antigen presentation compared with conventional BCG-CWS adjuvants. Subcutaneous immunization with the BCNA-based nanovaccine effectively targets lymph nodes, eliciting robust innate and tumor-specific immune responses. Importantly, our findings demonstrate that BCNAs significantly enhance neoantigen immunogenicity while minimizing acute systemic toxicity. Furthermore, when combined with a mouse PD-L1 antibody, our strategy achieves complete tumor elimination in 60% of cases and prevents 25% of tumor growth in a melanoma mouse model. In conclusion, our BCNA-based nanovaccine represents a promising avenue for advancing personalized therapeutic neoantigen vaccines and holds significant implications for enhancing personalized immunotherapy and improving patient outcomes in the field of cancer treatment.

Prostate cancer (PCa) is one of the leading causes of death for men worldwide. Unlike some other types of cancer, there is a lack of targeted therapy for prostate cancer patients that can kill cancer cells but do much less damage to the normal tissue. In this paper, we report on an adenoviral vector enhanced prostate cancer specific transferrin conjugated drug targeted therapy. In particular, a functional PCa-specific gene probe is introduced to drive and up-regulate the transferrin receptor expression on the PCa via adenoviral vector. As a result, significantly enhanced accumulation of nanoscale transferrin-doxorubicin (Tf-DOX) protein drug conjugates and concomitant notably elevated PCa tumor inhibition are observed. This conceptual strategy provides the proof-of-concept for the targeted therapy of PCa that is highly desired but not yet developed.

An Ionospheric Observation Network for Irregularity and Scintillation in East/Southeast Asia was recently deployed. Using ionospheric total electron content (TEC) from the two crossed Beidou geostationary satellite receiver chains of the network along 110°E and 23°N and Doppler velocity measurements from the Sanya (18.3°N, 109.6°E) portable digital ionosonde, we report first observations of low latitude TEC oscillations synchronized over a wide longitude range in East/Southeast Asia, which occur at nighttime, after the main phase of the geomagnetic storm on 20 April 2018. A comparison among TEC and Doppler velocity and interplanetary magnetic field (IMF) Bz component shows that the periodic TEC enhancements correlate with Fregion downward plasma drifts and IMF Bz southward turnings. The results suggest that the quasiperiodic southward turnings of IMF Bz could produce multiple short‐lived westward prompt penetration electric fields, which contribute to driving the nighttime low latitude TEC oscillations simultaneously over the wide longitude range. Regional‐scale positive/negative ionospheric storm effects have been widely investigated using GPS total electron content (TEC) and ionosonde observations. Here we report significant nighttime TEC oscillations detected at latitudes lower than the equatorial ionization anomaly crest in the longitudes of 95–120°E by the Ionospheric Observation Network for Irregularity and Scintillation in East/Southeast Asia during geomagnetic storm. Periodic TEC enhancements are nearly synchronized over the wide longitude range, in close association with downward plasma drifts at low latitude. The good consistence between the changes of plasma vertical drift and of interplanetary magnetic field Bz polarity indicates that multiple short‐lived westward prompt penetration electric fields could drive the periodic downward plasma drifts, which are very likely to cause low‐pressure region of topside ionosphere at low latitude and subsequent flowing of plasma from higher latitudes (equatorial ionization anomaly crest) to the low‐pressure region. The extra plasma sourced from higher latitudes, which is against the loss of increased recombination due to Fregion height decrease, could contribute to the TEC oscillations. Compared with the TEC measurements by GPS receiver network that are affected by satellite motion, the Ionospheric Observation Network for Irregularity and Scintillation in East/Southeast Asia, which measures TEC at fixed ionospheric pierce points along the same longitude/latitude by receiving Beidou geostationary satellite signals, provides a unique means for fine‐scale observations of ionospheric perturbations not previously possible. We report first IONISE observations of low latitude TEC oscillations synchronized over a wide longitude range at nighttimeThe TEC oscillations were likely driven by multiple westward PPEFs due to southward turnings of IMF BzThe IONISE provides a unique means for fine‐scale observations of ionospheric perturbations along the same longitude/latitude

The near‐polar orbit satellites of Swarm mission provide a good opportunity to investigate the conjugacy of equatorial plasma irregularities (EPIs) since their trajectories at low latitudes are basically aligned with fixed geographical longitude. However, the Swarm in situ electron density occasionally shows EPIs at only one hemisphere at this longitude. In this study, we provide detailed analysis of such EPI events from the in situ electron densities and onboard global positioning system (GPS) measurements of Swarm low pair satellites, and simultaneous GPS data from two geomagnetically conjugate ground stations at the Africa longitudes. The result indicates that when Swam in situ electron density sometime shows EPIs at only one hemisphere, the GPS scintillations are still observed from the Swarm onboard receiver and by the two conjugate ground stations. It implies that the EPIs should generally elongate along the geomagnetic flux tube. More than two‐year statistic results show that the onset time of scintillation in the northern station is on average 16 and 18 min earlier than that in the southern station for September equinox and December solstice in 2015, while for March equinox in 2016 the onset time of scintillation of northern station is about 11 min later than that of southern station, which indicates the asymmetry features of EPIs along the flux tube. Further analysis of nearly three‐year GPS data from two conjugate stations at the Asia longitudes, we find that during solar maximum years the local sunset time plays an important role for causing the difference of onset time of scintillation between two conjugate stations. The Swarm in situ electron density occasionally shows equatorial plasma irregularities at only one hemisphereThe scintillations caused by equatorial plasma irregularities observed by two geomagnetically conjugate ground stations agree well with each otherThe different onset time of scintillation at two conjugate stations indicates the asymmetry features of EPIs along the flux tube

ABSTRACTTumor markers of bladder cancer (BC) have been investigated for many years, but the clinical treatment based on these biomarkers is still unsatisfactory. STK32C, a member of the serine/threonine protein kinase of AGC superfamily, was first found to be highly expressed in brain tissues; however, the role of STK32C in malignant disease has not been determined. Data from TCGA database showed that the STK32C gene is overexpressed in BC and a number of other human tumors. In the current study, immunohistochemistry revealed that high expression of STK32C protein in tumor tissues was significantly associated with poor clinico pathologic features and a short relapse-free survival (RFS) in patients with BC. Slicing of STK32C inhibited tumor cell proliferation, migration and invasion in vitro. In vivoanimal experiments demonstrated that knocking-down of STK32C restricted the growth of tumor cells in mice. Finally, microarray analysis revealed that silencing of STK32C inhibited the activity of the HMGB1 pathway and regulated the expression of key genes in this pathway. In conclusion, our study showed novel promoting roles for STK32C in human tumors, which may provide a new therapeutic target for the patients with BC.

The bottom‐type irregularity scattering layer (BSL) that can appear in the ionospheric Fregion bottomside has been observed generally after sunset, serving as a possible telltale of equatorial spread F(ESF). Using simultaneous multibeam radar measurements over two low‐latitude stations, Sanya (18.3°N, 109.6°E; dip latitude 13°N) and Fuke (19.3°N, 109.1°E; dip latitude 14°N) in China, we report, for the first time, a thin BSL that initially occurred at presunset (~1720 LT), much earlier than the occurrence of BSL generated from the equatorial plasma shear vortex‐driven instability. The presunset BSL was situated around 225 km altitude and continued to exist until the appearance of ESF plumes after sunset (~1930 LT). Interestingly, the Doppler velocities of the presunset BSL echoes measured by the radar and the Flayer virtual heights obtained from the collocated Digisonde measurements over Sanya both show oscillations with a period of about 1 h, suggesting a close link between the occurrences of the BSL and of Fregion plasma density large‐scale wave structure before sunset. These observations could imply an important role of gravity waves in the generation of the presunset Fregion bottom‐type irregularities. First observation of Fregion bottom‐type irregularity scattering layer (BSL) generated before sunsetSimilar oscillations found in BSL echo Doppler velocity and Flayer heightThe presunset BSL could be linked with the presunset Fregion bottomside large‐scale wave structure

A single-frequency 1014.8 nm Yb-doped fiber amplifier working at room temperature was investigated in detail with respect to gain fiber length, fiber geometry, and fiber host material, which can be frequency quadrupled to 253.7 nm for laser cooling of mercury. After optimization, an up to 8.06 W laser was achieved with a single-stage amplifier, and 19.3 W power was obtained with another boost amplifier, using polarization-maintaining Yb-doped single-mode fiber with a 10 μm core and 125 μm inner clad. The amplified spontaneous emission was 25 dB lower than the signal in the final output of the laser system. The laser has a linewidth of ∼24  kHz without noticeable broadening after amplification. Further power scaling is limited by stimulated Brillouin scattering.

Three isostructural porous Prussian blue analogues KM[CrCN6]·H2O M = Zn, Mn, Fe with alkali metal cations K+located within the pores of the frameworks have been constructed and characterized structurally. Thermal gravimetric analysis and variabletemperature powder XRD results indicate that the three porous materials are stable at high temperatures, and their frameworks are still retained after dehydration. The permanent porosities have been confirmed by nitrogen and hydrogen sorption measurements at 77 K. Sorption studies show that the framework of FeCr with just 289 m2 g–1BET surface area can take up a moderate amount of H2at 77 K and 860 Torr [112 cm3STP g–1, 0.71 wt.], which indicates that the guest alkali metal cation K+located in the pores can enhance the H2binding affinity within the dehydrated porous framework.

A high-performance transportable fountain clock is attractive for use in laboratories with high-precision time-frequency measurement requirements. This Letter reports the improvement of the stability of a transportable rubidium-87 fountain clock because of an optimization of temperature characteristics. This clock integrates its physical packaging, optical benches, microwave frequency synthesizers, and electronic controls onto an easily movable wheeled plate. Two optical benches with a high-vibration resistance are realized in this work. No additional adjustment is required after moving them several times. The Allan deviation of the fountain clock frequency was measured by comparing it with that of the hydrogen maser. The fountain clock got a short-term stability of 2.3×10^−13 at 1 s and long-term stability on the order of 10^−16 at 100,000 s.

We experimentally observe polarization spectroscopy (PS) of the S_01-P3_1 transition of mercury atom gases at 253.7 nm. The PS signal can be observed in all six richly abundant isotopes and the PS signal of six transitions for laser cooling are all clear and of a dispersive line shape. The optimized pump power and probe power are found for the PS of Hg202. We find the linearly polarized component in the pump beam will distort the original PS signal due to the use of linear PS. Consequently, the purity of the pump beam is crucial to laser frequency stabilization by PS.