Structural modulation of aggregation-induced emission luminogens for NIR-II fluorescence imaging/photoacoustic imaging of tumors.

Concurrent near-infrared-II (NIR-II) fluorescence imaging (FLI) and photoacoustic imaging (PAI) holds tremendous potential for effective disease diagnosis owing to their combined benefits and complementary features, in particular on the basis of a single molecule. However, the simultaneous guarantee of high-quality NIR-II FLI and PAI is recognized to be challenging impeded by the competitive photophysical processes at the molecular level. Herein, a simple organic fluorophore, namely T-NSD, is finely engineered with facile synthetic procedures through delicately modulating the rigidity and electron-withdrawing ability of the molecular acceptor. The notable advantages of fabricated T-NSD nanoparticles include a large Stokes shift, intense fluorescence emission in the NIR-II region, and anti-quenching properties in the aggregated states, which eventually enable the implementation of dual-modal NIR-II FLI/PAI in a 4T1 tumor-xenografted mouse model with reliable performance and good biocompatibility. Overall, these findings present a simple strategy for the construction of NIR-II optical agents to allow multimodal disease diagnosis.

Pt Loading of Phosphorus-Doped Carbon Nanotube Aerogels in Fuel Cell-Type Gas Sensors for Ultrasensitive H2 Detection.

A phosphorus-doped carbon nanotube (CNT) aerogel as the support material was loaded with Pt nanoparticles in fuel cell-type gas sensors for ultrasensitive H2 detection. The high surface area of the CNT scaffold is favorable to providing abundant active sites, and the high electrical conductivity facilitates the transport of carriers generated by electrochemical reactions. In addition, the CNT aerogel was doped with phosphorus (P) to further enhance the conductivity and electrochemical catalytic activity. As a result, the fuel cell-type gas sensor using the Pt/CNT aerogel doped with the optimal P content as the sensing material shows considerable performance for H2 detection at room temperature. The sensor exhibits an ultrahigh response of -921.9 µA to 15,000 ppm of H2. The sensitivity is -0.063 µA/ppm, which is 21 times higher than that of the conventional Pt/CF counterpart. The sensor also exhibits excellent repeatability and humidity resistance, as well as fast response/recovery; the response/recovery times are 31 and 4 s to 3000 ppm of H2, respectively. The modulation of the structure and catalytic properties of the support material is responsible for the improvement of the sensor performance, thus providing a feasible solution for optimizing the performance of fuel cell-type gas sensors.

Unrestricted molecular motions enable mild photothermy for recurrence-resistant FLASH antitumor radiotherapy.

Ultrahigh dose-rate (FLASH) radiotherapy is an emerging technology with excellent therapeutic effects and low biological toxicity. However, tumor recurrence largely impede the effectiveness of FLASH therapy. Overcoming tumor recurrence is crucial for practical FLASH applications. Here, we prepared an agarose-based thermosensitive hydrogel containing a mild photothermal agent (TPE-BBT) and a glutaminase inhibitor (CB-839). Within nanoparticles, TPE-BBT exhibits aggregation-induced emission peaked at 900 nm, while the unrestricted molecular motions endow TPE-BBT with a mild photothermy generation ability. The balanced photothermal effect and photoluminescence are ideal for phototheranostics. Upon 660-nm laser irradiation, the temperature-rising effect softens and hydrolyzes the hydrogel to release TPE-BBT and CB-839 into the tumor site for concurrent mild photothermal therapy and chemotherapy, jointly inhibiting homologous recombination repair of DNA. The enhanced FLASH radiotherapy efficiently kills the tumor tissue without recurrence and obvious systematic toxicity. This work deciphers the unrestricted molecular motions in bright organic fluorophores as a source of photothermy, and provides novel recurrence-resistant radiotherapy without adverse side effects.

Unlocking the NIR-II AIEgen for High Brightness through Intramolecular Electrostatic Locking.

Fluorescent imaging and biosensing in the near-infrared-II (NIR-II) window holds great promise for non-invasive, radiation-free, and rapid-response clinical diagnosis. However, it's still challenging to develop bright NIR-II fluorophores. In this study, we report a new strategy to enhance the brightness of NIR-II aggregation-induced emission (AIE) fluorophores through intramolecular electrostatic locking. By introducing sulfur atoms into the side chains of the thiophene bridge in TSEH molecule, the molecular motion of the conjugated backbone can be locked through intramolecular interactions between the sulfur and nitrogen atoms. This leads to enhanced NIR-II fluorescent emission of TSEH in both solution and aggregation states. Notably, the encapsulated nanoparticles (NPs) of TSEH show enhanced brightness, which is 2.6-fold higher than TEH NPs with alkyl side chains. The in vivo experiments reveal the feasibility of TSEH NPs in vascular and tumor imaging with a high signal-to-background ratio and precise resection for tiny tumors. In addition, polystyrene nanospheres encapsulated with TSEH are utilized for antigen detection in lateral flow assays, showing a signal-to-noise ratio 1.9-fold higher than the TEH counterpart in detecting low-concentration antigens. This work highlights the potential for developing bright NIR-II fluorophores through intramolecular electrostatic locking and their potential applications in clinical diagnosis and biomedical research.

Donor-Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR-II Emission.

Photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and nonspecific organelle targeting hinder their therapeutic effectiveness. Herein, a donor-acceptor modulation approach is reported to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near-infrared (NIR-II) window. By employing dithieno[3,2-b:2',3'-d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP-In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR-II region. The reduced energy gap between singlet and triplet states in DTP-In also increases the reactive oxygen species (ROS) generation rate. Further, DTP-In can self-assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP-In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660 nm laser irradiation. This work highlights the potential of molecular engineering of donor-acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy.

An All-Rounder for NIR-II Phototheranostics: Well-Tailored 1064 nm-Excitable Molecule for Photothermal Combating of Orthotopic Breast Cancer.

The second near-infrared (NIR-II, 1000-1700 nm) light-activated organic photothermal agent that synchronously enables satisfying NIR-II fluorescence imaging is highly warranted yet rather challenging on the basis of the overwhelming nonradiative decay. Herein, such an agent, namely TPABT-TD, was tactfully designed and constructed via employing benzo[c]thiophene moiety as bulky electron donor/π-bridge and tailoring the peripheral molecular rotors. Benefitting from its high electron donor-acceptor strength and finely modulated intramolecular motion, TPABT-TD simultaneously exhibits ultralong absorption in NIR-II region, intense fluorescence emission in the NIR-IIa (1300-1500 nm) region as nanoaggregates, and high photothermal conversion upon 1064 nm laser irradiation. Those intrinsic advantages endow TPABT-TD nanoparticles with prominent fluorescence/photoacoustic/photothermal trimodal imaging-guided NIR-II photothermal therapy against orthotopic 4T1 breast tumor with negligible adverse effect.

Manipulation of aurophilicity in constructed clusters of gold(I) complexes with boosted luminescence and smart responsiveness.

High-performance luminescent gold(I) complexes have attracted considerable attention due to their potential applications in various fields, but their construction is a significantly challenging task. Herein, we designed and synthesized a series of novel dinuclear gold(I) complexes 1-4 based on 1,2-bis(diphenylphosphino)benzene and 1,4-bis(diphenylphosphino)benzene frameworks, where para-substitutions of benzene ring were employed for comparison and bulky t-butyl groups were introduced into carbazole ligands to assist flexibly regulating the aurophilicity. Among them, the structure of complex 1 was confirmed by single-crystal X-ray diffraction, and all the complexes exhibited typical aggregation-induced emission characteristics. Due to the construction of intramolecular aurophilicity and the formation of molecular clusters, noticeable enhancement of the luminescent efficiency was achieved for the core complex 1. Together with the introduction of flexible t-butyl groups, good responsiveness towards external mechanical force and solvent vapors were also realized. Moreover, the specific bioimaging ability of complex 1 towards cancer cells was demonstrated. Thus, this work presents the crucial capability of aurophilic manipulation in tuning the luminescence and smart behaviors of gold complexes, and it will open a new route to developing high-performance luminescent materials.

Influences of coexisting aged polystyrene microplastics on the ecological and health risks of cadmium in soils: A leachability and oral bioaccessibility based study.

Whether coexisting microplastics (MPs) affect the ecological and health risks of cadmium (Cd) in soils is a cutting-edge scientific issue. In this study, four typical Chinese soils were prepared as artificially Cd-contaminated soils with/without aged polystyrene (PS). TCLP and in vitro PBET model were used to determine the leachability (ecological risk) and oral bioaccessibility (human health risk) of soil Cd. The mechanisms by which MPs influence soil Cd were discussed from direct and indirect perspectives. Results showed that there was no significant difference in the leachability of soil Cd with/without aged PS. Additionally, aged PS led to a significant decrease in the bioaccessibility of soil Cd in gastric phase, but not in small intestinal phase. The increase in surface roughness and the new characteristic peaks (e.g., Si-O-Si) of aged PS directly accounted for the change in Cd bioaccessibility. The change in organic matter content indirectly accounted for the exceptional increase in Cd bioaccessibility of black soil with aged PS in small intestinal phase. Furthermore, the changes in cation exchange capacity and Cd mobility factor caused by aged PS explained the change in Cd leachability. These results contribute to a deeper understanding about environmental and public health in complicated emerging scenarios.

PATrans: Pixel-Adaptive Transformer for edge segmentation of cervical nuclei on small-scale datasets.

Transformer has shown excellent performance in various visual tasks, making its application in medicine an inevitable trend. Nevertheless, simply using transformer for small-scale cervical nuclei datasets will result in disastrous performance. Scarce nuclei pixels are not enough to compensate for the lack of CNNs-inherent intrinsic inductive biases, making transformer difficult to model local visual structures and deal with scale variations. Thus, we propose a Pixel Adaptive Transformer(PATrans) to improve the segmentation performance of nuclei edges on small datasets through adaptive pixel tuning. Specifically, to mitigate information loss resulting from mapping different patches into similar latent representations, Consecutive Pixel Patch (CPP) embeds rich multi-scale context into isolated image patches. In this way, it can provide intrinsic scale invariance for 1D input sequences to maintain semantic consistency, allowing the PATrans to establish long-range dependencies quickly. Futhermore, due to the existing handcrafted-attention is agnostic to the widely varying pixel distributions, the Pixel Adaptive Transformer Block (PATB) effectively models the relationships between different pixels across the entire feature map in a data-dependent manner, guided by the important regions. By collaboratively learning local features and global dependencies, PATrans can adaptively reduce the interference of irrelevant pixels. Extensive experiments demonstrate the superiority of our model on three datasets(Ours, ISBI, Herlev).

More Is Better: Dual-Acceptor Engineering for Constructing Second Near-Infrared Aggregation-Induced Emission Luminogens to Boost Multimodal Phototheranostics.

The manipulation of electron donor/acceptor (D/A) shows an endless impetus for innovating optical materials. Currently, there is booming development in electron donor design, while research on electron acceptor engineering has received limited attention. Inspired by the philosophical idea of "more is different", two systems with D'-D-A-D-D' (1A system) and D'-D-A-A-D-D' (2A system) structures based on acceptor engineering were designed and studied. It was demonstrated that the 1A system presented a weak aggregation-induced emission (AIE) to aggregation-caused quenching (ACQ) phenomenon, along with the increased acceptor electrophilicity and planarity. In sharp contrast, the 2A system with one more acceptor exhibited an opposite ACQ-to-AIE transformation. Interestingly, the fluorophore with a more electron-deficient A-A moiety in the 2A system displayed superior AIE activity. More importantly, all compounds in the 2A system showed significantly higher molar absorptivity (ε) in comparison to their counterparts in the 1A system. Thanks to the highest ε, near-infrared-II (NIR-II, 1000-1700 nm) emission, desirable AIE property, favorable reactive oxygen species (ROS) generation, and high photothermal conversion efficiency, a representative member of the 2A system handily performed in fluorescence-photoacoustic-photothermal multimodal imaging-guided photodynamic-photothermal collaborative therapy for efficient tumor elimination. Meanwhile, the NIR-II fluorescence imaging of blood vessels and lymph nodes in living mice was also accomplished. This study provides the first evidence that the dual-connected acceptor tactic could be a new molecular design direction for the AIE effect, resulting in high ε, aggregation-intensified NIR-II fluorescence emission, and improved ROS and heat generation capacities of phototheranostic agents.

Hepatitis B reactivation in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.

BACKGROUND: Immunotherapy shows promise as a treatment option for various cancers. However, there is growing concern over potential complications from hepatitis B virus (HBV) reactivation after checkpoint blockade immunotherapy. Although most of the previous clinical trials on immune checkpoint inhibitors (ICIs) excluded patients with HBV, a few case reports and retrospective studies of HBV reactivation have been published. The aim of this study is to assess the risk of hepatitis B virus reactivation (HBVr) in patients receiving ICIs for advanced cancer. METHODS: English and Chinese language literature published prior to April 30, 2023, was searched in PubMed, EMBASE, Web of Science, Cochrane, SinoMed, CNKI and Wanfang Data for studies reporting HBVr rates in cancer patients treated with ICIs. A pooled risk estimate was calculated for HBVr rates with 95% confidence intervals (CI). RESULTS: Data from 34 studies including 7126 patients were retrieved and analyzed. The pooled HBVr rate in cancer patients treated with ICIs was 1.3% (I2 = 90.44%, 95% CI: 0.2-2.9%, P < 0.001). Subgroup analysis revealed that patients diagnosed with hepatocellular carcinoma (HCC), HBV carriers, and patients from Asian regions or in developing countries have a higher rate of HBVr. CONCLUSIONS: Our meta-analysis demonstrated a low risk of HBVr in patients treated with ICIs for advanced cancer. ICI treatment may be safely used in patients with existing HBV infection or chronic hepatitis B, accompanied by regular monitoring and appropriate antiviral prophylaxis if necessary.

Binding Affinity Studies of Nicotinamide N-methyltransferase and Ligands by Saturation Transfer Difference NMR.

INTRODUCTION: Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of nicotinamide with S-adenosine-L-methionine (SAM) as the methyl donor. Abnormal expression of NNMT is associated with many diseases (such as multiple cancers and metabolic and liver diseases), making NNMT a potential therapeutic target. Limited studies concerning the enzymesubstrate/ inhibitor interactions could be found to fully understand the detailed reaction mechanism. METHODS: The binding affinity and ligand binding epitopes of nicotinamide or SAH for binding NNMT and its mutants were determined using saturated transfer difference (STD) nuclear magnetic resonance (NMR) techniques combined with site-directed mutagenesis. RESULTS: The average dissociation constant of WT NNMT with nicotinamide and S-adenosine homocysteine (SAH) was 5.5 ± 0.9 mM and 1.2 ± 0.3 mM, respectively, while the mutants Y20F and Y20G with nicotinamide were up to nearly 4 times and 20 times that of WT and with SAH nearly 2 times and 5 times that of WT. The data suggested that WT had the highest binding affinity for nicotinamide or SAH, followed by Y20F and Y20G, which was consistent with its catalytic activity. CONCLUSION: The binding affinity of nicotinamide and SAH to NNMT and its mutants were obtained by STD NMR in this study. It was found that nicotinamide and SAH bind to WT in a particular orientation, and Y20 is critical for their binding orientation and affinity to NNMT.

Activation of Pyroptosis Using AIEgen-Based sp2 Carbon-Linked Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have emerged as a promising class of crystalline porous materials for cancer phototherapy, due to their exceptional characteristics, including light absorption, biocompatibility, and photostability. However, the aggregation-caused quenching effect and apoptosis resistance often limit their therapeutic efficacy. Herein, we demonstrated for the first time that linking luminogens with aggregation-induced emission effect (AIEgens) into COF networks via vinyl linkages was an effective strategy to construct nonmetallic pyroptosis inducers for boosting antitumor immunity. Mechanistic investigations revealed that the formation of the vinyl linkage in the AIE COF endowed it with not only high brightness but also strong light absorption ability, long lifetime, and high quantum yield to favor the generation of reactive oxygen species for eliciting pyroptosis. In addition, the synergized system of the AIE COF and αPD-1 not only effectively eradicated primary and distant tumors but also inhibited tumor recurrence and metastasis in a bilateral 4T1 tumor model.

A New Strategy to Elevate Absorptivity of AIEgens for Intensified NIR-II Emission and Synergized Multimodality Therapy.

High-efficiency absorptivity is crucial for the construction of high-performance luminescent materials, especially the long-wavelength near-infrared II (NIR-II) materials; thus seeking an efficient and universal strategy to elevate the absorptivity is extremely important but is still an intractable challenge. In this work, a simple but efficient design strategy is discovered, involving the introduction of gold(I) unit that could effectively elevate the absorptivity of aggregation-induced-emission luminogens (AIEgens). As a result of the efficient elevation of absorptivity, the representative AIE-active TBTP-Au shows more superior NIR-II (1220 nm) luminescence, much higher photothermal conversion efficiency, and unique intracellular reactive oxygen species (ROS) generating ability compared with that of the TBTP ligand. Taking advantage of these improvements, the fabricated tumor-targeting TBTP-Au-cRGD nanoparticles achieve specific NIR-II tumorous imaging in vivo and exert high-efficiency cancer therapy via the synergistic chemotherapy and photothermal therapy. Thus, this work provides a new and efficient strategy to construct high-absorption luminescent materials and demonstrates the great potential of gold(I)-based AIEgens as multifunctional theranostic agents.

Tailoring the Amphiphilic Structure of Zwitterionic AIE Photosensitizers to Boost Antitumor Immunity.

Although photodynamic therapy (PDT) for thorough cancer treatment is hindered by the limited generation of reactive oxygen species (ROS) with short lifetime from photosensitizers, PDT-induced antitumor immune response remedies the defects. Previous studies show that inducing immunogenic cell deaths is an attractive approach to activate antitumor immunity, which confers a robust adjuvanticity to dying cancer cells. In this work, amphiphilic luminogens with aggregation-induced emission characteristics (AIEgens) are rationally designed and synthesized. By modulating the hydrophobic π-bridge and zwitterionic functional groups, these AIEgens exhibit tunable organelle specificity to lysosome, endoplasmic reticulum, and plasma membrane and enhance ROS generation ability. Notably, the membrane-targeting AIEgen namely TPS-2 induces cell death and membrane rupture via PDT to facilitate the release of antigens and activation of immune cells. Furthermore, the size-controlled TPS-2 nanoaggregates are found to serve as an adjuvant, promoting antigen accumulation and delivery to sufficiently boost the in vivo antitumor immunity by only one dose injection in a prophylactic tumor vaccination model. This work thus provides new insights into optimizing AIE photosensitizers via a hydrophobicity-hydrophilicity balance strategy for evoking an antitumor immunity and directly suppressing the distanced tumor. A single small-molecular system for PDT-stimulated antitumor immunity is envisioned.

Lipidome remodeling activities of DPA-EA in palmitic acid-stimulated HepG2 cells and the in vivo anti-obesity effect of the DPA-EA and DHA-EA mixture prepared from algae oil.

Background: The nuclear receptor Nur77 has been demonstrated to play a vital role in the inflammatory response and cellular metabolisms, and its ligands exhibit efficacy in the treatment of inflammation-related diseases (e.g., improving mouse acute lung injury (ALI) and obesity. Recently, ω-3 polyunsaturated fatty acid-ethanolamine derivatives (ω-3 PUFA-EAs), including DPA-EA and DHA-EA, have been reported as new Nur77-targeting anti-inflammatory agents. However, the lipid-lowering effect of ω-3 PUFA-EAs is still unknown, and lipid profile changes induced by Nur77-targeting anti-inflammatory agents also remain unclear. Objective: This study aimed to evaluate the lipid-lowering effect and the underlying mechanism of DPA-EA acting as Nur77-targeting anti-inflammatory agents. It also aimed to investigate the in vitro and in vivo lipid-lowering effects of the DPA-EA and DHA-EA mixture prepared from algae oil. Methods: The in vitro lipid-lowing effect of DPA-EA and its mixture with DHA-EA was first evaluated in palmitic acid-stimulated HepG2 Cells. To confirm the lipid-lowering effect and explore the underlying mechanism, we performed untargeted lipidomic analysis using ultra-performance liquid chromatography/triple quadrupole-time-of-flight (TOF) mass spectrometry coupled with multivariate statistical analysis, with another Nur77-targeting anti-inflammatory compound Celastrol (Cel) as a reference. Finally, we examined the anti-obesity effect of the DPA-EA and DHA-EA mixture synthesized from algae oil in a high-fat diet (HFD)-fed mice model. Results: DPA-EA significantly alleviated lipid accumulation with lower toxicity than Celastrol. Nur77-targeting compounds DPA-EA and Celastrol could simultaneously reduce 14 lipids (9 TGs, 2 PCs, 1 PA, 1 SM, and 1 LacCer) and increase 13 lipids (4 DGs, 6 LPEs, 2 PEs, and 1PC) in Pal-stimulated HepG2 cells. However, Cer lipids were more sensitive to DPA-EA, while the over-downregulation of SM lipids might be associated with the off-target toxicity of Celastrol. The mixture of DPA-EA and DHA-EA synthesized from algae oil could significantly decrease TG, TC, and LDL levels and increase HDL levels in HFD-fed mice, exerting an excellent anti-obesity effect. Conclusion: Nur77-targeting anti-inflammatory compound DAP-EA could promote the hydrolysis of PEs and TGs to ameliorate lipid accumulation. The DPA-EA and DHA-EA mixture prepared from algae oil might be a potential therapeutic agent for obesity and other inflammation-related diseases.

Machine Learning-Assisted Volatile Organic Compound Gas Classification Based on Polarized Mixed-Potential Gas Sensors.

The performance of electrochemical gas sensors depends on the reactions at the three-phase boundary. In this work, a mixed-potential gas sensor containing a counter electrode, a reference electrode, and a sensitive electrode was constructed. By applying a bias voltage to the counter electrode, the three-phase boundary can be polarized. The polarization state of the three-phase boundary determined the gas-sensitive performance. Taking 100 ppm ethanol vapor as an example, by regulating the polarization state of the three-phase boundary, the response value of the sensor can be adjusted from -170 to 40 mV, and the sensitivity can be controlled from -126.4 to 42.6 mV/decade. The working temperature of the sensor can be reduced after polarizing the three-phase boundary, lowering the power consumption from 1.14 to 0.625 W. The sensor also showed good stability and short response-recovery time (3 s). Based on this sensor, the Random Forest algorithm reached 99% accuracy in identifying the kind of VOC vapors. This accuracy was made possible by the ability to generate several signals concurrently. The above gas-sensitive performance improvements were due to the polarized three-phase boundary.

Clinical characteristics of second primary malignancies among first primary malignancy survivors: A single-center study, 2005-2020.

The cancer survivor population is growing due to advances in detection and treatment. For improved long-term patient management, it is critical to examine the clinical characteristics and outcomes of second primary malignancies (SPMs). An SPM is defined as a second distinct pathological diagnosis, with the same or different origin as the first primary malignancy (FPM). In the present retrospective study, categorical clinical variables were compared between subgroups and the impact on overall survival was evaluated. A total of 1,188 patients with an FPM were included, of which 102 experienced an SPM (8.59%). When compared with the patients who did not develop an SPM, patients with an SPM were significantly older at first diagnosis, had a higher pathological stage and higher rates of biliary tract disease and thyroid disease. In addition, patients with an SPM were more likely to have received postoperative chemotherapy (28.43 vs. 12.16%, P<0.0001) and to be long-term consumers of cigarettes and alcohol (25.00 vs. 8.95%, P<0.05). In addition, an increase in the number of regimens received but not in the number of courses of chemotherapy was associated with a reduction in the time interval to SPM development. Non-small cell lung cancer (NSCLC) was the most common type of FPM (18.27%). In patients with NSCLC the occurrence of SPMs was relatively low (5.07%) and the SPM-associated mortality rate was 2.30%. Breast cancer was the second common type of FPM (12.09%). Patients with breast cancer had a relatively high likelihood of developing an SPM (9.30%), for which family history of malignancy and postoperative chemotherapy were identified as potential risk factors. Patients with stomach cancer were the most vulnerable to SPM (17.95%) and patients with digestive tract cancer had the longest time interval between the FPM and SPM development. In addition, thyroid adenoma was identified as a potential risk factor for SCLC. The findings of the present study may provide valuable guidance for the short- and long-term monitoring of FPM survivors.

De Novo Design of Reversibly pH-Switchable NIR-II Aggregation-Induced Emission Luminogens for Efficient Phototheranostics of Patient-Derived Tumor Xenografts.

Phototheranostics has received sustained attention due to its great potential in revolutionizing conventional strategies of cancer treatment. However, trapped by the complexity, poor reproducibility, insufficient phototheranostic outputs, and inevitable damage to normal tissue of most multicomponent phototheranostic systems, its clinical translation has been severely hindered. Therefore, the exploration of "one for all" smart phototheranostic agents with versatile functionalities remains an appealing yet enormously challenging task. Herein, a reversibly pH-switchable and near-infrared second photosensitizer featuring aggregation-induced emission was tactfully designed by molecular engineering for precise tumor-targeting fluorescence imaging-guided phototherapy. Thanks to the strong intramolecular charge transfer, enhanced highly efficient intersystem crossing, and sufficient intramolecular motion, the developed agent DTTVBI was endowed with boosted type-I superoxide anion radical generation and excellent photothermal performance under 808 nm laser irradiation. More importantly, DTTVBI nanoparticles with high biocompatibility exhibit remarkably enhanced type-I photodynamic/photothermal therapy in the tumor region, thus offering significant antitumor effects both in vitro and in the patient-derived tumor xenograft model of colon cancer. This work sheds new light on the development of superior versatile phototheranostics for cancer therapy.

Effect of Berberine Hydrochloride on the Diversity of Intestinal Flora in Parkinson's Disease Patients.

This study aimed to investigate the effect of berberine hydrochloride on the diversity of intestinal flora in patients with Parkinson's disease (PD). Prospectively selected 68 PD patients, admitted to our hospital from April 2021 to June 2021, were randomly assigned to an observation group and a control group (n = 34 per group). Patients in the control group were given conventional treatment in accordance with Parkinson's diagnosis and treatment guidelines. Patients in the observation group were administered berberine hydrochloride besides the treatment in the control group. After continuous treatment for 3 months, the enzyme-linked immunosorbent assay was applied to determine interleukin-8 (IL-8), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. High-throughput sequencing technology was employed to perform DNA sequencing on the 16S rRNA genes of all bacteria in stool samples before and after treatment in the two groups to analyze the distribution of intestinal flora. After treatment, the levels of IL-8, IL-6, and TNF-α were lower in the observation group than those in the control group (P < 0.05). Regarding intestinal flora, the Chao index, Ace index, and Shannon index were higher in the observation group than those in the control group. The Simpson index was lower in the observation group than that of the control group (P < 0.05). The principal component analysis chart analysis exhibited that the overall structure of the intestinal flora was quite different between the observation and the control groups after treatment. Berberine hydrochloride can improve the disorder of intestinal flora in PD patients and suppress the expression of inflammatory factors.