Tumor Microenvironment-Regulating Two-Photon Probe Based on Bimetallic Post-Coordinated MOF Facilitating the Dual-Modal and Deep Imaging-Guided Synergistic Therapies.

The intricate tumor microenvironment (TME) always brings about unsatisfactory therapeutic effects for treatments, although nanomedicines have been demonstrated to be highly beneficial for synergistic therapies to avoid the side effects caused by the complexity and heterogeneity of cancer. Developing nanotheranostics with the functionalities of both synergistic therapies and TME regulation is a good strategy but is still in its infancy. Herein, an "all-in-one" nanoplatform for integrated diagnosis and treatment, namely, Carrier@ICG@DOX@FA (CIDF), is constructed. Benefiting from the bimetallic coordination of Eu3+-HTHA (4,4,4-trifluoro-1-(9-hexylcarbazol-3-yl)-1,3-butanedione) and Fe3+ with the ligands in UiO-67, CIDF can simultaneously achieve two-photon fluorescence imaging, fluorescent lifetime imaging in deep tumors, and regulation of TME. Owing to its porosity, CIDF can encapsulate indocyanine green as photosensitizers and doxorubicin as chemotherapeutic agent, further realizing light-controlled drug release. Moreover, CIDF exhibited good biocompatibility and tumor targeting by coating with folic-acid-modified polymers. Both in vitro and in vivo experiments demonstrate the excellent therapeutic efficacy of CIDF through dual-modal-imaging-guided synergistic photothermal-, photodynamic-, and chemotherapy. CIDF provides a new paradigm for the construction of TME-regulated synergistic nanotheranostics and realizes the complete elimination of tumors without recurrence.

Rationally designed Ru(ii)-metallacycle chemo-phototheranostic that emits beyond 1000 nm.

Ruthenium complexes are emerging as potential complements to platinum drugs. They also show promise as photo-diagnostic and therapeutic agents. However, most ruthenium species studied to date as potential drugs are characterized by short excitation/emission wavelengths. This limits their applicability for deep-tissue fluorescence imaging and light-based therapeutic treatments. Here, we report a Ru(ii) metallacycle (Ru1100) that emits at ≥1000 nm. This system possesses excellent deep-tissue penetration capability (∼7 mm) and displays good chemo-phototherapeutic performance. In vitro studies revealed that Ru1100 benefits from good cellular uptake and produces a strong anticancer response against several cancer cell lines, including a cisplatin-resistant A549 cell line (IC50 = 1.6 µM vs. 51.4 µM for cisplatin). On the basis of in vitro studies, it is concluded that Ru1100 exerts its anticancer action by regulating cell cycle progression and triggering cancer cell apoptosis. In vivo studies involving the use of a nanoparticle formulation served to confirm that Ru1100 allows for high-performance NIR-II fluorescence imaging-guided precise chemo-phototherapy in the case of A549 tumour mouse xenografts with no obvious side effects. This work thus provides a paradigm for the development of long-wavelength emissive supramolecular theranostic agents based on ruthenium.

NIR-II Emissive Ru(II) Metallacycle Assisting Fluorescence Imaging and Cancer Therapy.

Despite the success of emissive Ruthenium (Ru) agents in biomedicine, problems such as the visible-light excitation/emission and single chemo- or phototherapy modality still hamper their applications in deep-tissue imaging and efficient cancer therapy. Herein, an second nearinfrared window (NIR-II) emissive Ru(II) metallacycle (Ru1000, λem  = 1000 nm) via coordination-driven self-assembly is reported, which holds remarkable deep-tissue imaging capability (≈6 mm) and satisfactory chemo-phototherapeutic performance. In vitro results indicate Ru1000 displays promising cellular uptake, good cancer-cell selectivity, attractive anti-metastasis properties, and remarkable anticancer activity against various cancer cells, including cisplatin-resistant A549 cells (IC50  = 3.4 × 10-6  m vs 92.8 × 10-6  m for cisplatin). The antitumor mechanism could be attributed to Ru1000-induced lysosomal membrane damage and mitochondrial-mediated apoptotic cell death. Furthermore, Ru1000 also allows the high-performance in vivo NIR-II fluorescence imaging-guided chemo-phototherapy against A549 tumors. This work may provide a paradigm for the development of long-wavelength emissive metallacycle-based agents for future biomedicine.

Novel simulation of aqueous total nitrogen and phosphorus concentrations in Taihu Lake with machine learning.

This study demonstrates the utility of internal nutrient loads as an additional parameter to improve the performance of machine learning models in predicting the temporal variations of aqueous TN and TP concentrations in Taihu Lake, a large shallow lake. Internal loads, as a potential input parameter for machine learning models, were estimated using a mass balance calculation. The results showed that between 2011 and 2018 the maximum monthly internal loads of nitrogen and phosphorus in Taihu Lake were 4200 t and 178 t, respectively. Monthly changes in the aqueous TN and TP concentrations of Taihu Lake did not correlate significantly with inflow loads whereas the correlations with estimated internal loads were positive and significant. Long short-term memory (LSTM), random forest (RF), and gradient boosting regression tree (GBRT) models were built, and for all of them the inclusion of internal loads in the input parameters improved their performance. LSTM model III, whose input parameters included both inflow loads and internal loads, had the best performance, based on a testing root mean square error of 0.11 mg TN/L and 0.017 mg TP/L. A 28 % decrease in the annual aqueous TP concentration in Taihu Lake in 2018 simulated by LSTM model III was achieved by lowering the average water level from 3.29 m to 2.99 m, suggesting a possible strategy to control the TP concentration in the lake. In summary, our study showed that aqueous TN and TP concentrations in shallow lakes can be simulated using machine learning, with LSTM models outperforming RF and GBRT models; in these models, internal loads should be included as an input parameter. Additionally, our study identified the water level as an important factor affecting the aqueous TP concentration in Taihu Lake.

Rigidity Bridging Flexibility to Harmonize Three Excited-State Deactivation Pathways for NIR-II-Fluorescent-Imaging-Guided Phototherapy.

Small organic phototherapeutic molecules of the second near-infrared (NIR-II) window (1000-1700 nm) serve as promising candidates for theranostics. However, developing such versatile agents for fluorescence-guided photodynamic/photothermal therapy remains a demanding task stirred by competitive energy dissipation pathways, including radiative decay, internal conversion, and intersystem crossing. To the best of current knowledge, the current paradigm for addressing the issue has deliberately approached the optimum balance among three deactivation processes through offsetting from each other, possibly leading to a comprehensively compromised theranostic efficacy. Few reports aim to modulate the three deactivation pathways excluding sacrificing any one of them. Herein, a molecular design strategy to construct a phototherapeutic organic fluorophore CCNU-1060, armed with NIR-II luorescence-guided phototherapeutic properties, is rationally developed. With a flexible motor, tetraphenylethene, bridged to the rigidified coplanar core boron-azadipyrromethene, the desired CCNU-1060 is subsequently encapsulated into an amphiphilic matrix to form CCNU-1060 nanoparticles (NPs), which match or transcend its precursor NJ-1060 NPs in the three energy dissipation processes. CCNU-1060 NPs are utilized to realize high-spatial vessel imaging and effective NIR-II fluorescence-guided phototherapeutic tumor ablation. This study unlocks a viewpoint of molecular engineering that simultaneously regulates multiple energy dissipation pathways for the construction of versatile phototherapy agents.

Rapid monitoring of heavy metal pollution in lake water using nitrogen and phosphorus nutrients and physicochemical indicators by support vector machine.

A novel method of predicting heavy metal concentration in lake water by support vector machine (SVM) model was developed, combined with low-cost, easy to obtain nutrients and physicochemical indicators as input variables. 115 surface water samples were collected from 23 sites in Chaohu Lake, China, during different hydrological periods. The particulate concentrations of heavy metals in water were much higher than the dissolved concentrations. According to Nemerow pollution index (Pi), pollution degrees by Fe, V, Mn and As ranged from heavy (2 ≤ Pi < 4) to serious (Pi ≥ 4). The concentrations of most heavy metals were the highest during the medium-water period and the lowest during the dry season. Non-metric Multidimensional Scaling Analysis confirmed heavy metal concentrations had slight spatial difference but relatively large seasonal variation. Redundancy Analysis indicated the close associations of heavy metals with nutrient and physicochemical indicators. When both nutrient and physicochemical indicators were used as input variables, the simulation effects for most elements in total and particulate were relatively better than those obtained using only nutrient or only physicochemical indicators. The simulation effects for As, Ba, Fe, Ti, V and Zn were generally good, based on their training R values of 0.847, 0.828, 0.856, 0.867, 0.817 and 0.893, respectively, as well as their test R values of 0.811, 0.836, 0.843, 0.873, 0.829 and 0.826, respectively; and meanwhile, in both the training and test stages, these metals also had relatively lower errors. The spatial distribution of heavy metals in Chaohu Lake was then predicted using the fully trained SVM models.

Acupuncture for hot flashes in women with breast cancer: A systematic review.

BACKGROUND: Acupuncture is applied worldwide in treating hot flashes (HFs), which may be a common complication experienced by women with breast cancer (BC). Although researches associated with the effect of acupuncture for HFs have been done by many people, there is a lack of comprehensive evaluation of the effect of this therapy. OBJECTIVE: The aim of this systematic review is to assess the effectiveness of acupuncture for HFs in women with BC. METHODS: Seven databases (Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, Chinese National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, and Wan Fang Database) were searched from their inceptions to June 2015 without language restrictions. Randomized controlled trials (RCTs) were aggregated to evaluate the therapeutic effect of acupuncture for HFs in women with BC. RESULTS: Twelve RCTs were identified at last, and all of the studies agreed on the potential therapeutic effect of acupuncture for HFs in women with BC. However, three trials showed significant difference compared with the controls. One research demonstrated an encouraging trend, and six did not find any difference between acupuncture and controls. Another two trials got a negative result compared with hormone therapy. The meta-analysis indicated a difference in the number of HFs after treatment and during follow-up compared with the controls. Three trials reported Kupperman index scores, and meta-analysis showed significant difference between acupuncture and controls after treatment and during follow-up. CONCLUSION: Acupuncture seems to be an effective therapy for HFs in women with BC; however, there was insufficient evidence to support the efficacy of acupuncture. However, the results should be interpreted cautiously, because of the poor quality and small number of included studies.

Effect of miniscalpel-needle on relieving the pain of myofascial pain syndrome: a systematic review.

OBJECTIVE: To evaluate the effect and safety of miniscalpel-needle (MSN) on reducing the pain of myofascial pain syndrome (MPS). METHODS: We reviewed the available literatures inception up to February 2014 using Pubmed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure Database, Chinese Biomedical Database and Wanfang Database. RESULTS: Eight randomized controlled trials were finally identified. The main controls involved acupuncture, medications, injection, massage and cupping. We found that all of the studies agreed on the potential benefit of MSN as a strategy for MPS and the superiority compared to the controls, however, randomized methods applied in most of the trials could be criticized for their high or unclear risk of bias. Further research is also needed to clarify questions around the appropriate frequency and number of treatment sessions of MSN. CONCLUSION: This review shows that MSN might have the effect on MPS, even though there were some limitations in the studies included in the review. Studies with robust methodology are warranted to further test its pain-relieving effect on MPS.